The ABC’s of the AHA/ACC Prevention Guidelines

The ABC’s of the AHA/ACC Prevention Guidelines
Alessandra Calvo-Friedman, Andrew DeFilippis, MD, Ty Gluckman MD, Dominique Ashen, CRNP, PhD, Roger Blumenthal, MD, Johns Hopkins Ciccarone Preventive Cardiology Center The ABC prevention guidelines provide a simplified approach to prevention of coronary heart disease (CHD). The guidelines present important lifestyle changes and risk-reducing drug therapies to help to prevent cardiovascular events. They are based on the American Heart Association (AHA) and American College of Cardiology (ACC) guidelines, which are periodically updated. It is best to talk to your own health care provider about ways to lower your risk of a heart attack or stroke. We hope that these guidelines will provide a good background to enhance your understanding of what is known about heart attack prevention. This teaching slide kit is in an ABC format and covers: 1) Aspirin and similar drugs, 2) ACE Inhibitors and Similar Drugs, 3) Blood pressure, 4) Cholesterol, 5) Cigarette Smoking, 6) Diet and Weight Issues, and 7) Persons with low Ejection Fractions

Definition Primary Prevention: Modification of risk factors or prevent their development to prevent or delay the onset of CHD. Secondary Prevention: Initiation of Rx to reduce recurrent CHD events in patients with CHD. Primary and a Half Prevention*: As individuals with subclinical CHD are identified, the distinction between primary and secondary prevention becomes blurred. Coronary heat disease (CHD) is diagnosed when your coronary arteries, the arteries that carry blood to the heart, become narrowed with the buildup of plaques within the artery wall. The process of plaque buildup is called atherosclerosis and hinders the ability of the body to pump enough blood through the arteries to provide adequate oxygen and nutrients to the heart. CHD is the #1 cause of death in both men and women in the United States and can lead to angina (recurrent chest pain), heart attacks, heart failure, and arrhythmias (abnormal heart rhythms). The development of atherosclerosis is a slow process and typically occurs after decades of lifestyle behaviors that lead to the accumulation of cells, fats, and cholesterol on the inner lining of the arteries. The process typically starts when the layer of cells that line the arteries, the endothelium, is damaged because of exposure to toxins such as cigarette smoke, high blood pressure, high cholesterol, or elevated blood sugar. Primary prevention aims to avoid the initial development of CHD. Risk factors for CHD include older age, family history of early CHD, diabetes, cigarette smoking, high LDL (bad) cholesterol levels, low high-density lipoprotein (HDL) (good) cholesterol levels, and high blood pressure. Changes in lifestyle behaviors can help to prevent the development of CHD. Secondary prevention provides individuals diagnosed with CHD therapies to prevent futures cardiac events. In addition to modifications in lifestyle behaviors, drugs can help to control blood lipid levels, lower blood pressure, and decrease the risk of blood clots and future cardiac events. Rx = Treatment CHD = Coronary Heart Disease Subclinical: refers to asymptomatic buildup of plaque that may be detected using imaging studies such as a cardiac CT scan or ultrasound of the neck arteries. CHD=Coronary heart disease *Celermajer DS. JACC 2005;45:1994-6

Aspirin Recommendations
Primary Prevention Aspirin ( mg daily) in intermediate risk men with a 10 year risk of CHD >10%. Aspirin ( mg daily) in intermediate risk women > 65 yrs with a 10 yr risk of CHD >10% Aspirin in low risk women with a 10 year risk of CHD <10%. I IIa IIb III B Antiplatelet Medications: Aspirin Throughout this presentation, the ABC prevention guidelines will be classified using the Class I, II a, II b, and III categories. Class I guidelines are highly recommended. Class IIa guidelines have conflicting evidence but are still recommended while class IIb guidelines have conflicting evidence and studies are still needed to further address this question. Class III guidelines are not recommended. Within classes I, II a, II b, and III, recommended therapies or procedures are categorized as A, B, or C levels of evidence. A indicates that the guideline is highly recommended within its class while B or C indicates that evidence is not as strong. Throughout the presentation, we refer to an individuals’ 10-year risk of a heart attack. This 10-year risk of a heart attack is based on the Framingham risk score. The way in which a persons’ Framingham risk score is determined in discussed later in the presentation. Antiplatelet medications are a class of medications that help to prevent platelets (a type of blood cell) from forming a blood clot that could cause a heart attack. Aspirin is a type of antiplatelet agent that is frequently utilized in the primary prevention of CHD. Aspirin is sometimes recommended for people who have no signs of CHD or other cardiovascular disease but have one or more risk factors for a heart attack. Daily aspirin ( mg daily) is routinely prescribed and highly recommended for men at “intermediate” risk (10 year risk of CHD > 10%). Daily aspirin ( mg) is also often utilized for women with a 10 year risk of CHD > 10%. Aspirin is usually not used to prevent heart attack in a woman with less than a 10% 10 year risk of heart attack unless she has multiple cardiac risk factors and is postmenopausal. Aspirin is sometimes recommended in women < 65 years of age for ischemic stroke prevention. (Class IIB, Level B) CHD=Coronary heart disease

Aspirin Recommendations (Continued)
Secondary Prevention Aspirin ( mg daily) in those with known CHD or carotid artery or leg artery narrowings due to plaque. Aspirin ( mg daily) in those that have undergone CABG surgery*. Daily aspirin is routinely prescribed to people who have already had a heart attack, known coronary artery disease, diabetes, or known narrowed arteries in another part of the body with the goal of preventing a second cardiac event. By taking aspirin over the long term, someone with CHD can reduce his/her risk of a recurrence of stroke, heart attack, and cardiovascular death by about 25% or more. Additionally, chewing a regular dose aspirin immediately after the onset of heart attack symptoms can increase the chances of surviving a heart attack. CABG=Coronary artery bypass graft, CHD=Coronary heart disease *To be administered within the first 48 hours after surgery in order to reduce the risk of saphenous vein graft failure. Doses >162 mg/day may be continued for up to one year.

Physicians’ Health Study (PHS)
Aspirin Evidence: Primary Prevention in Men Physicians’ Health Study (PHS) 22,071 men randomized to aspirin (325mg every other day) followed for an average of 5 years Aspirin significantly reduces the risk of MI in men The Physicians' Health Study demonstrated the benefit of aspirin for the primary prevention of cardiovascular disease in men. In the study, 22,071 men were randomized to aspirin (325 mg every other day) and were followed for an average of 5 years. The study concluded that daily low-dose aspirin decreases the risk of a first heart attack by 44% though the absolute difference between the groups was only about 1%. A Relative Risk of 0.56 means that the there was 44% risk reduction in the relative risk of heart attacks observed. CI=Confidence interval, MI=Myocardial infarction Physicians’ Health Study Research Group. NEJM 1989;321:129-35

Womens’ Health Study (WHS)
Aspirin Evidence: Primary Prevention in Women Womens’ Health Study (WHS) 39,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years Aspirin doesn’t reduce the risk of MI in women Aspirin Placebo Incidence of MI Cumulative The Women’s Health Study examined the effect of aspirin in the prevention of a first heart attack in women. 39,876 women were randomized to aspirin (100 mg every other day) or placebo for an average of 10 years. The study found that aspirin does not reduce the risk of a heart attack in low-risk women. The routine use of aspirin in low-risk women with a 10 year risk of hard CHD events of (<10%) should be generally be avoided unless prescribed by a physician. However, women over age 65 seemed to benefit from low-dose aspirin. P=0.83 Years MI=Myocardial infarction Ridker P et al. NEJM 2005; 352:

Clopidogrel Evidence: Secondary Prevention
Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial 12,562 patients with a NSTE-ACS randomized to daily aspirin ( mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin for 9 months Aspirin + Clopidogrel Aspirin + Placebo Rate of death, myocardial infarction, or stroke P<0.001 Antiplatelet Medication: Clopidogrel Clopidogrel is another type of antiplatelet medication. It works by a different mechanism than aspirin and is typically used over a shorter period of time (~1 year or less) to prevent the formation of blood clots. Clopidogrel is generally used in combination with aspirin to prevent the formation of blood clots. It is often used in patients at high risk of CHD and in people who have had a heart attack, unstable angina, or those who have had an angioplasty with or without implantation of a drug-eluting stent. Unstable angina is a condition in which an inadequate supply of blood and oxygen reach the heart, usually because of a blood clot that is partially occluding the coronary artery. Like a heart attack, unstable angina is a medical emergency and is a sign that a heart attack could occur soon. Clopidogrel is also frequently used in combination with aspirin by individuals that have had unstable angina or a heart attack. The CURE trial provided strong evidence for combining clopidogrel with aspirin rather than just using aspirin alone for such individuals. Participants who received clopidogrel after experiencing unstable angina (300 mg immediately, followed by 75 mg once daily) in addition to aspirin had fewer adverse cardiovascular events than those receiving aspirin alone. More patients in the clopidogrel and aspirin group had bleeding episodes, but there were not significantly more patients with episodes of life-threatening bleeding or hemorrhagic strokes. 3 6 9 12 Months of Follow Up DAP=Dual antiplatelet therapy, NSTE-ACS=Non ST-segment elevation acute coronary syndrome The CURE Trial Investigators. NEJM. 2001;345:

ACE Inhibitor Recommendations
Secondary Prevention An ACE inhibitor in those following a MI, regardless of EF or in those with CAD* along with hypertension (SBP >120 mmHg), LVSD (EF <0.40), heart failure, DM, or CKD. Optional use of an ACE inhibitor in those with low risk CAD*, well controlled CV risk factors, a normal EF, and successful revascularization. I IIa IIb III B ACE Inhibitors ACE inhibitors are a type of antihypertensive (blood pressure lowering medication) that are used to reduce the risk of recurring CHD events. “ACE” stands for angiotension-converting enzyme and ACE inhibitors works to lower blood pressure by decreasing the production of angiotension II, a substance that constricts the arteries. By decreasing the production of angiotension II and relaxing the blood vessels, blood can move through the blood vessels at a lower pressure. The use of ACE inhibitors is strongly recommended for individuals that have had a heart attack and those with CHD with hypertension. ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, CKD=Chronic kidney disease, CV=Cardiovascular, DM=Diabetes mellitus, EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, SBP=Systolic blood pressure *Defined by previous MI or angiographically significant CAD.

ACE Inhibitor Evidence: Secondary Prevention
Heart Outcomes Prevention and Evaluation (HOPE) Study 9,297 patients with DM or vascular disease plus one additional CV risk factor, but without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years ACE-I reduce CV events in high-risk individuals 0.20 Ramipril 0.15 Placebo CV death, MI, or stroke (%) 0.10 0.05 22% RRR, P<0.001 0.00 500 1000 1500 The Heart Outcomes Prevention and Evaluation (HOPE) Study evaluated the effect of the ACE inhibitor ramipril in patients with a high risk of future cardiovascular event. Participants in the study either had diabetes mellitus or cardiovascular disease plus one additional cardiovascular risk factor, but had not experienced heart failure or had known left ventricular systolic dysfunction (LVSD) (weakened heart muscle). The study found that a 10-mg dose of ramipril in comparison with placebo reduced the incidence of death, heart attack, and stroke from cardiovascular causes by 22% . The study concluded that ramipril significantly reduces the rates of death, heart attack, and stroke in a broad range of high-risk patients. Days of Follow-Up ACE-I=Angiotensin converting enzyme inhibitors, DM=Diabetes mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction HOPE Investigators. NEJM 2000;342:

Digitalis: Recommendations
Secondary Prevention I IIa IIb III B Digitalis in those with symptomatic HF and LVSD (EF <45%) to reduce hospitalizations for HF*. Digitalis in those with asymptomatic LVSD and normal sinus rhythm. Heart failure is caused by a weakening of the heart’s ability to pump blood. The most common cause of heart failure is heart damage due to CHD or high blood pressure. A number of drugs are used to manage heart failure, including ACE inhibitors, diuretics, beta-blockers, and digitalis. Digitalis is a type of drug that may help to reduce hospitalizations for heart failure in patients with an ejection fraction <45%. EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function *Contraindications include significant sinus or atrioventricular block unless a permanent pacemaker is present.

Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial 8,290 patients with stable coronary artery disease and normal left ventricular function randomized to trandolapril (4 mg) or placebo for 5 years ACE-I do not reduce CV events in low-risk individuals 30 25 20 15 10 5 Placebo Trandolapril Primary End Point (%)* The Prevention of Events with Angiotension Converting Enzyme Inhibition (PEACE) trial tested the effect of the ACE inhibitor trandolapril on individuals with stable coronary artery disease, normal or slightly reduced left ventricular function, and those receiving “current standard” therapy. Compared to placebo, trandolapril failed to show a significant reduction in death from cardiovascular causes, heart attack, or coronary revascularization (the restoration of blood to the heart through bypass or other surgery). However, the study found that an ACE inhibitor does seem to slow the progression from metabolic syndrome to diabetes. Years After Randomization *Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization PEACE Trial Investigators. NEJM 2004;351:

Comparison between the HOPE and PEACE trials MI, Cardiac death, or Stroke (%) The incidence of heart attack, cardiac death, or stroke was lower in the PEACE trial than in that observed in the HOPE trial. This likely reflects the greater percentage of individuals receiving modern risk reducing therapies in PEACE than in HOPE. 70% of people in PEACE received lipid-lowering therapy while only 29% of people enrolled in HOPE received these medications. This may explain why trandolapril, unlike ramipril, failed to show a significant reduction in cardiovascular events. Years Patients enrolled in the PEACE trial were at lower risk* *Reflects greater blood pressure control, revacularization, and use of other risk-reducing medications (i.e., antiplatelet therapy, b-blocker, lipid-lowering medication) CHD=Coronary heart disease, MI=Myocardial infarction Braunwald, E. et al., NEJM 2004;351:

AIRE Clinical and/or radiographic signs of HF SAVE Radionuclide EF £ 40% TRACE Echocardiogram EF £ 35% 0.05 0.15 0.2 0.25 0.3 1 2 3 0.35 0.4 4 Placebo ACE-I Probability of Event 0.1 OR: 0.74 (0.66–0.83) This study reviewed data from patients from 5 long-term randomized trials that assessed ACE inhibitors in patients with left-ventricular dysfunction or heart failure. Three of the trials enrolled patients within a week after an acute myocardial infarction. In all 5 trials, the ACE-inhibitor group had lower rates of death than the placebo group, and lower rates of a repeated heart attack and readmission for heart failure. The study concluded that ACE inhibitors lower rates of mortality, heart attack, and hospital admission for heart failure in patients with left-ventricular dysfunction or heart failure with or without a recent heart attack. ACE-I provide substantial benefit in post-MI LVSD Years ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio Flather MD, et al. Lancet. 2000;355:1575–1581

Blood Pressure FDR had a long history of hypertensive heart disease and Stalin realized that FDR was not as sharp as he was at the Yalta Conference.

By the time of the Yalta conference, FDR’s BP was ~230/130.

JNC VII Guidelines for Measurement of BP
Provides information on response to therapy. May help improve adherence to therapy and evaluate “white-coat” HTN. Self-measurement Indicated for evaluation of “white-coat” HTN. Absence of 10–20% BP decrease during sleep may indicate increased CVD risk. Ambulatory BP monitoring Two readings, 5 minutes apart, sitting in chair. Confirm elevated reading in contralateral arm. In-office Brief Description Method High blood pressure (hypertension) affects almost one in three adults. It often has no warning signs but can cause serious damage to the blood vessels and make the heart work harder. Hypertension also increases the development of atherosclerosis and, thus, can reduce the blood supply to the heart. As a result, it is important to monitor blood pressure regularly both in the doctor’s office and at home. The classification of hypertension is based on a mean of two readings at two separate visits to the doctor. The initial BP reading is generally higher. It is important to be seated for 5 minutes before taking the second reading. Blood pressure is considered normal if it is below 120/80 mmHg (millimeters of mercury). The upper number is the systolic blood pressure, which measures the pressure in the arteries while the heart is pumping blood. The bottom number is the diastolic pressure, which measures the pressure in the arteries while the heart relaxes between beats. Prehypertension is a condition in which either the systolic pressure is between 120 and 140 mmHg or the diastolic blood pressure is between 80 and 89 mmHg. Individuals with prehypertension are at increased risk of developing high blood pressure. Stage I hypertension is diagnosed when the systolic blood pressure is mmHg, or the diastolic blood pressure is mmHg. Stage II hypertension is diagnosed when the systolic blood pressure is greater than 160 or the diastolic blood pressure is > Many people older than 50 have a condition called isolated systolic hypertension in which the systolic blood pressure is elevated but the diastolic blood pressure is normal. This type of hypertension is associated with an increased risk of heart attack and reducing systolic blood pressure with treatment can greatly reduce this risk. BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension Chobanian AV et al. JAMA. 2003;289:

Blood Pressure: Risk Increases with Age
National Health and Nutrition Examination Survey (NHANES) III 72% 66% 51% 38% Percent hypertensive 18% 9% 3% A representative sample from the National Health and Nutritional Examination Survey (NHANES III, phases 1 and 2) demonstrated that approximately 25% of the US adult population has hypertension, and the prevalence of hypertension increases sharply with advancing age. In this survey, an individual with hypertension either had blood pressure greater than or equal to 140/90 mmHg or was already on medications to lower blood pressure. 18-29 30-39 40-49 50-59 60-69 70-79 80+ Age Hypertension defined as blood pressure >140/90 mmHg or treatment JNC-VI. Arch Intern Med. 1997;157:

Blood Pressure: Lower is Better
Ischemic Heart Disease Mortality Age at Risk (Y) Age at Risk (Y) 80-89 80-89 256 128 64 32 16 8 4 2 1 256 128 64 32 16 8 4 2 1 70-79 70-79 60-69 60-69 50-59 50-59 Ischemic Heart Disease Mortality Ischemic Heart Disease Mortality 40-49 40-49 Among a broad age range, there is a direct relationship between high blood pressure and death due to cardiovascular disease, without any evidence of a threshold down to at least 115/75 mm Hg. 120 140 160 180 80 90 100 110 70 Usual Systolic BP (mm Hg) Usual Diastolic BP (mm Hg) BP=Blood pressure Prospective Studies Collaboration. Lancet. 2002;360:

JNC VII Causes of Secondary Hypertension
Medical Conditions Chronic kidney disease Primary hyperaldosteronism Renovascular disease Chronic steroid therapy Cushing’s syndrome Pheochromocytoma Aortic coarctation Thyroid or parathyroid disease Sleep apnea Drugs NSAIDS Oral contraceptives Adrenal steroids Sympathomimetics Cyclosporine or tacrolimus Erythropoietin Ephedra, mu huang, bitter orange Cocaine or amphetamines Alcohol There are a number of medical conditions and drugs that can cause hypertension. While these secondary causes of high blood pressure are less common, they may require specific treatment when identified. Certain medical conditions such as chronic kidney disease, thyroid disease, and sleep apnea can elevate blood pressure. About half of all people with sleep apnea, for example, have high blood pressure. NSAIDS=Non-steroidal anti-inflammatory drugs Chobanian AV et al. JAMA. 2003;289:

JNC VII Lifestyle Modifications for BP Control
Recommendation Approximate SBP Reduction Range Weight reduction Maintain normal body weight (BMI= ) 5-20 mmHg/10 kg weight lost Adopt DASH eating plan Diet rich in fruits, vegetables, low fat dairy and reduced in fat 8-14 mmHg Restrict sodium intake <2.4 grams of sodium per day 2-8 mmHg Physical activity Regular aerobic exercise for at least 30 minutes on most days of the week 4-9 mmHg Moderate alcohol consumption <2 drinks/day for men and <1 drink/day for women 2-4 mmHg Lifestyle modification can lead to significant reductions in blood pressure. Some people may be able to reduce their blood pressure to a normal range with lifestyle modification alone. Lifestyle modifications that help to lower blood pressure include weight reduction and maintenance of a normal body weight, eating a diet rich in fruits, vegetables, low-fat dairy, and low-fat foods, restricting sodium intake, increasing physical activity, and consuming a moderate amount of alcohol. BMI=Body mass index, SBP=Systolic blood pressure Chobanian AV et al. JAMA. 2003;289:

JNC VII Guidelines for Management and Treatment
Two-drug combination for most† (usually thiazide-type diuretic and ACEI or ARB or BB or CCB). Yes >100 >160 Stage 2 Hypertension Drug(s) for the compelling indications.‡ Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. 90–99 140–159 Stage 1 Hypertension Drug(s) for compelling indications. ‡ No antihypertensive drug indicated. 80–89 120–139 Prehypertension Encourage <80 <120 Normal With compelling indications Without compelling indication Initial drug therapy Lifestyle modification DBP* mmHg SBP* mmHg BP classification and or or or If lifestyle modifications are not capable of lowering blood pressure to the desired level, medications will most likely be prescribed. Compelling indications refer to treatments that have shown efficacy for a particular population in large randomized controlled trials. For individuals with prehypertension ( /80-89), no antihypertensive drug will usually be prescribed. For those with stage 1 hypertension ( /90-99), a thiazide-type diuretic and/or another antihypertensive drug will be prescribed for most people. Individuals with stage II hypertension (blood pressure greater than 160/100), will often receive a two drug combination that usually includes a thiazide-type diuretic and another medication such as an ACE inhibitor, an ARB, a beta blocker, or a calcium channel blocker. ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=b-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure *Treatment determined by highest blood pressure category. †Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡Treat patients with chronic kidney disease or diabetes mellitus to blood pressure goal of <130/80 mmHg. Chobanian AV et al. JAMA. 2003;289:

Blood Pressure Recommendations
Secondary Prevention Initiation or maintenance of lifestyle modification in those with a BP >120/80 mmHg. Use of an ACE inhibitor and/or b-blocker in those with a BP >140/90 mmHg*. Other drugs (i.e., thiazide diuretics) should be added in order to achieve the desired BP. There are many drugs that can help to lower blood pressure. For individuals with established hypertension, the use of a medication to lower blood pressure is highly recommended. There are five classes of medications that are often used to lower blood pressure: diuretics, beta-blockers, ACE inhibitors, angiotension II receptor blockers (ARBs), and calcium channel blockers. Diuretics reduce blood pressure by increasing the amount of sodium and water that is excreted in the urine. In particular, Thiazide diuretics are the most commonly used diuretics because in addition to lowering blood pressure, they also reduce the risk of heart failure. Beta blockers also play an important role in lowering blood pressure by blocking the action of the hormone epinephrine (adrenaline). This lowers blood pressure by slowing the heart rate and decreasing the amount of blood pumped to the heart with each beat. ACE inhibitors lower blood pressure by inhibiting the formation of angiotension II, a substance that constricts blood vessels. Angiotension II receptor blockers lower blood pressure by interfering with the ability of angiotension II to constrict blood vessels. Finally, calcium channel blockers lower blood pressure by dilating arteries and decreasing the amount of blood the heart pumps with each beat. ACE=Angiotensin converting enzyme, BP=Blood pressure, CKD=Chronic kidney disease, DM=Diabetes mellitus *A BP >130/80 mmHg should be used for individuals with CKD or DM

Blood Pressure Evidence: Primary Prevention
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) 33,357 patients with HTN and >1 CHD risk factor randomized to chlorthalidone, amlodipine, or lisinopril for 5 years There is similar efficacy among BP lowering agents 1 2 3 4 5 6 7 .04 .08 .12 .16 .20 Chlrothalidone Amlodipine Lisinopril Rate of MI or fatal CHD RR (95% CI) P-value A/C 0.98 ( ) 0.65 L/C 0.99 ( ) 0.81 The objective of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was to evaluate whether therapy with a a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril) could lower the incidence of CHD or cardiovascular disease events compared to therapy with a diuretic (chlorthalidone). The study found that thiazide-type diuretics are similarly effective to the calcium channel blocker and the ACE inhibitor in preventing heart attack and cardiovascular death and are less expensive. The study concluded that the thiazide-type diuretics should be preferred for first-step antihypertensive therapy. If they are not prescribed as the initial drug, they should generally be the second antihypertensive agent added. Years to CHD Event BP=Blood pressure, CHD=Coronary heart disease, HTN=Hypertension, MI=Myocardial infarction ALLHAT Investigators. JAMA. 2002;288:

Blood Pressure Evidence: Primary Prevention
Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study 9,193 high-risk hypertensive* patients with LVH randomized to losartan (100 mg) or atenolol (100 mg) for 5 years An ARB provides greater efficacy in patients with LVH 16 Atenolol Losartan 12 Proportion with CV death, MI, or stroke (%) 8 4 13% RRR, P=0.021 The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study, compared the use an angiotension II receptor blocker (losartan) to a beta blocker (atenolol) in hypertensive patients with left ventricular hypertrophy (significant thickening of the heart muscle). The study found that the ARB prevents more cardiovascular morbidity and death than the beta blocker for a similar reduction in blood pressure and is better tolerated. The ARB also seemed to provide benefits beyond reduction in blood pressure such as protecting the heart, helping to prevent diabetes, kidney disease in people with diabetes, and strokes in people with high blood pressure and left ventricular hypertrophy (thickened heart muscle). The ARB reduced stroke incidence more than the beta blocker did. 6 12 18 24 30 36 42 48 54 60 66 Study Month ARBS=Angiotensin receptor blocker strategy, CV=Cardiovascular, DBP=Diastolic blood presure, LVH=Left ventricular hypertrophy, MI=Myocardial infarction, SBP=Systolic blood pressure *Defined by SBP= mmHg or DBP= mmHg Dahlöf B et al. Lancet. 2002;359:

Blood Pressure Evidence: Secondary Prevention
Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) Trial 1,991 patients with CAD and a DBP <100 mmHg randomized to amloidipine (10 mg), enalapril (20 mg), or placebo for 2 years A BP <130/80 mmHg is associated with fewer CV events 130/78 0.25 Placebo Follow-up BP (mmHg) 124/77 0.20 Enalapril 125/77 Amlodipine 0.15 CV event rate* 0.10 0.05 6 12 18 24 There previously was less certainty about the effect of antihypertensive medications in people with known CHD in order to lower blood pressure less than 140/90 mmHg. The Comparison of Amlodipine vs. Enalapril to Limit Occurrences in Thrombosis (CAMELOT) trial examined the effects of a calcium channel blocker (amlodipine) and an ACE inhibitor (enalapril) in patients with CAD and normal blood pressure. The study found that the use of the calcium channel blocker amlodipine by patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. The use of the ACE inhibitor (enalapril) had a smaller and less significant impact on the cardiovascular event rate than the use of the calcium channel blocker. Months BP=Blood pressure, CAD=Coronary artery disease, CV=Cardiovascular, DBP=Diastolic blood pressure, HF=Heart failure, MI=Myocardial infarction, PAD=Peripheral arterial disease, TIA=Transient ischemic attack *Includes CV death, MI, cardiac arrest, coronary revascularization, hospitalization for HF or angina pectoris, stroke, TIA, development of PAD Nissen S et al. JAMA 2004;292:

b-blocker Recommendations*
Secondary Prevention A b-blocker in all patients following a MI. A beta-blocker in all patients with LVSD. A b-blocker in those with other forms of CV disease or DM, unless contraindicated. I IIa IIb III C Beta Blockers Beta blockers are recommended for use by individuals with a history of a heart attack or impaired heart muscle function. In addition to lowering blood pressure, beta blockers also alleviate symptoms of angina, may improve heart muscle function, and reduce the risk of death and future heart attacks in people who have already had a heart attack. CV=Cardiovascular, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction *Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds.

b-blocker Evidence: Secondary Prevention
Summary of Secondary Prevention Trials of b-blocker Therapy Phase of Treatment Total # Patients RR (95% CI) Acute treatment 28,970 0.87 ( ) Secondary prevention 24,298 0.77 ( ) Overall 53,268 0.81 ( ) 0.5 1.0 2.0 The majority of large randomized clinical trials comparing beta blockers to placebo in individuals who have had a heart attack show a reduction in mortality and repeated heart attack. Overall, these studies demonstrate that the use of beta blockers reduce risk of future events by about 15-20% and confirm that beta blockers are a standard medication for the secondary prevention of cardiovascular disease. RR of death b-blocker better Placebo better CI=Confidence interval, RR=Relative risk Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A textbook of Cardiovascular Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168.

Cholesterol Management Guidelines
Secondary Prevention Restriction of saturated fat (<7% of total calories) and cholesterol (<200 mg/day) in all patients. Promotion of daily physical activity and weight management in all patients. Increase in w-3 fatty acid consumption in all patients. Cholesterol Lifestyle changes that lower total and LDL cholesterols are recommended for all individuals that already have CHD. People with diagnosed CHD should restrict their saturated fat intake. Saturated fat is present in most animal and dairy foods and in some oils. Consumption of fatty meats, full-fat dairy products, and certain vegetable oils and products (palm oil, coconut oil, palm kernel oil, and vegetable shortening) should be minimal. They should reduce their consumption of cholesterol-rich foods such as egg yolks, organ meats, and all types of flesh (beef, pork, poultry, lamb, and fish), and certain shellfish (such as shrimp). Plant foods such as fruits, vegetables, legumes, nuts, and cereals do not contain cholesterol. Omega-3 fat is a particular type of polyunsaturated fat that lowers triglyceride levels. This type of fat may also prevent life-threatening arrhythmias. Two specific types of these fats – eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – in particular have a beneficial effect on the heart. EPA and DHA are found in fatty fish such as salmon, sardines, herring, and mackerel, fish oil supplements, and a prescription medication called Lovaza. Omega-3 fats are also found in certain plants such as flaxseed, soybeans, walnuts, and canola oil; however, their cardiovascular benefit is still being investigated. The American Heart Association recommends eating fish at least twice a week to receive the benefit of the omega-3 fat found in fish. LDL-C=Low density lipoprotein cholesterol

Cholesterol Management Guidelines (Continued)
Secondary Prevention Initiation or intensification of LDL-C lowering drug therapy in those with a baseline or on-treatment LDL-C level >100 mg/dl. Initiation of LDL-C lowering drug therapy in those with a baseline LDL-C level <100 mg/dl based on clinical judgment. In addition to making lifestyle modifications, people diagnosed with CHD with an LDL cholesterol level above 100 mg/dl, should initiate or increase the dosage of a statin medication. For individuals with an LDL cholesterol level below 100 mg/dl, a statin should still be strongly considered. Statins are the most effective drug for lowering total and LDL cholesterol levels. These drugs block the action of an enzyme that is required for the liver to manufacture cholesterol. As a result, the liver makes less cholesterol and more LDL receptors that help to remove LDL cholesterol from the blood. Overall, statins produce a 25-55% reduction in LDL cholesterol, a 5-15% increase in HDL cholesterol, and a 10-25% reduction in triglycerides. LDL-C=Low density lipoprotein cholesterol

Goals Recommendations As set forth by the Adult Treatment Panel III (ATP III) National Cholesterol Education Program (NCEP) Obtain a fasting lipid profile in all patients. For those with a myocardial infarction, a fasting lipid profile should be obtained within 24 hrs of admission. Start therapeutic lifestyle changes in all patients, including: Reduced intakes of saturated fats (<7% of total calories) and cholesterol (<200 mg/day) Addition of plant stanols/sterols (2 g/day) and viscous fiber (10-25 g/day) to enhance LDL-C lowering Weight reduction Increased physical activity A fasting lipid profile should be obtained in all adults aged 20 years or older once every 5 years. Individuals with high levels of total and low-density lipoprotein (LDL) cholesterol in their blood have a greater risk of cholesterol depositing in the artery walls. The National Cholesterol Education Program recommends that people keep their cholesterol levels below certain levels. People who are diagnosed with CHD, have other cardiovascular diseases (for example, a historic of transient ischemic attack or stroke, peripheral arterial disease, or abdominal aortic aneurysm) need to aim for an LDL cholesterol level of less than 100 mg/dL, with an optional goal of less than 70 mg/dL. Having a high level of high-density lipoprotein in the blood is also important in the secondary prevention of cardiovascular events. HDL protects against CHD by transporting cholesterol to the liver from plaques in the arteries. Men should aim to have an HDL level of 40mg/dL and women should aim for an HDL level of 50mg/dL. An HDL level above 60mg/dL is preferable for both genders. Lifestyle modifications also help to lower cholesterol levels. In particular, the reduction in intake of saturated fats and cholesterol to less than 200 mg per day, reducing weight, and increasing physical activity helps to lower cholesterol levels. Consuming two grams a day of plant stanols and sterols and 10 to 25 grams of viscous fiber a day also may have an effect in lowering cholesterol. Stanols and sterols are cholesterol-lowering food additives that are added to a wide variety of foods such as orange juice, yogurt, and granola bars. Stanols and sterols have a similar structure to cholesterol. They compete with dietary cholesterol for absorption in the small intestine and thus prevent the absorption of some dietary cholesterol in the small intestine. Some studies have shown that consuming stanol- and sterol-fortified food reduce LDL cholesterol levels by up to 14% when used in combination with a low-saturated fat, low-cholesterol diet. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486.

Goals Recommendations As set forth by the Adult Treatment Panel III (ATP III) National Cholesterol Education Program (NCEP) For primary and secondary prevention, HMG-coA reductase inhibitors (statins) should be first-line in order to achieve the LDL-C goal. For those that remain above the LDL-C goal, statin therapy should be intensified along with the addition of a second LDL-C lowering agent if needed. If the TG level is >150 mg/dl or HDL-C level is <40 mg/dl, emphasize weight management, physical activity, and smoking cessation. If the TG level is mg/dl after initiation of LDL-C lowering therapy, consider adding nicotinic acid or a fibrate. If the TG level is >500 mg/dl, consider adding nicotinic acid or a fibrate before LDL-C lowering therapy. According to the Adult Treatment Panel III of the National Cholesterol Education Program, statins should be the main drug therapy to lower cholesterol. A fibrate, niacin, cholesterol absorption inhibitor, bile acid sequestrant, or omega-3 fatty acid supplement may be a second or third medication prescribed for high cholesterol. TG=Triglyceride Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486.

Risk Profile Assessment for LDL-C Lowering
A risk assessment tool* is needed for individuals with >2 RFs 10 20 2 RFs 0-1 RF 10-year CHD Risk CAD or Risk Equivalent** If someone has more than one risk factor for CHD, he/she should calculate his 10 year risk of CHD. Risk factors for CHD include: High blood pressure (140/90 mmHg or higher) or the use of a blood-pressure reducing medication Cigarette smoking HDL cholesterol level less than 40 mg/dl for men and less than 50 for women. Family history of early heart disease (before age 55 in a brother or father; before age 65 in a mother or sister) Age 45 or older if you’re a man; age 55 or older if you’re a woman CAD=Coronary artery disease, CHD=Coronary heart disease, DM=Diabetes mellitus, RF=Risk factor *Such as the Framingham Risk Score (FRS) **Includes DM, non-coronary atherosclerotic vascular disease, and >20% 10-year CHD risk by the FRS Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486.

McDonald’s used to be one of our former President’s favorite restaurants.
Passed torch: President and Mrs. Clinton exit McDonald’s after his symbolic passage of leadership.

Framingham Risk Score: Men
Step 1: Age Points Step 4: SBP Points Step 5: Smoking Status Points Years Points 20-34 -9 35-39 -4 40-44 45-49 3 50-54 6 55-59 8 60-64 10 65-69 11 70-74 12 75-79 13 SBP (mmHg) If untreated If treated <120 1 2 >160 3 Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Nonsmoker Smoker 8 5 3 1 Step 6: Sum of Points Age Total Cholesterol HDL-C Systolic Blood Pressure Smoking Status Point Total Step 2: Total Cholesterol Points Step 7: 10-year CHD Risk TC (mg/dl) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 4 3 2 1 7 5 9 6 >280 11 8 Point Total 10-year Risk <0 <1% 6 2% 13 12% 1% 7 3% 14 16% 1 8 4% 15 20% 2 9 5% 16 25% 3 10 6% >17 >30% 4 11 8% 5 12 10% Framingham Risk Score The Framingham risk score estimates a person’s likelihood of suffering a CHD event – a heart attack, unstable angina, the need for an angioplasty or bypass surgery, or a CHD-related death – over the next 10 years. The risk-scoring system bases CHD risk on age, blood pressure, cholesterol levels, and smoking habits. To calculate risk, evaluate each of the five risk factors and determine the number of points received for each. Then add up the total number of points and use the sum to find the 10-year CHD risk factor. The 10-year CHD risk score is calculated differently for men and women. This table represents the table used for calculated a man’s risk score. Step 3: HDL-C Points HDL-C (mg/dl) Points >60 -1 50-59 40-49 1 <40 2

Framingham Risk Score: Women
Step 1: Age Points Step 4: SBP Points Step 5: Smoking Status Points Years Points 20-34 -7 35-39 -3 40-44 45-49 3 50-54 6 55-59 8 60-64 10 65-69 12 70-74 14 75-79 16 SBP (mmHg) If untreated If treated <120 1 3 2 4 5 >160 6 Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Nonsmoker Smoker 9 7 4 2 1 Step 6: Sum of Points Age Total Cholesterol HDL-C Systolic Blood Pressure Smoking Status Point Total Step 2: Total Cholesterol Points Step 7: 10-year CHD Risk TC (mg/dl) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 4 3 2 1 8 6 11 5 >280 13 10 7 Point Total 10-year Risk <9 <1% 15 3% 22 17% 9 1% 16 4% 23 22% 10 17 5% 24 27% 11 18 6% >25 >30% 12 19 8% 13 2% 20 11% 14 21 14% This table represents a woman’s 10-year risk score. Step 3: HDL-C Points HDL-C (mg/dl) Points >60 -1 50-59 40-49 1 <40 2

ATP III LDL-C Goals and Cut-points for Drug Therapy
Risk Category LDL-C Goal Initiate TLC Consider Drug Therapy High risk: CHD or CHD risk equivalents (10-year risk >20%) <100 mg/dL (optional goal: <70 mg/dL) 100 mg/dL >100 mg/dL (<100 mg/dL: consider drug options) Moderately high risk: 2+ risk factors* (10-year risk 10% to 20%) <130 mg/dL (optional goal: <100 mg/dL) 130 mg/dL >130 mg/dL ( mg/dL: consider drug options) Moderate risk: 2+ risk factors* (10 year risk <10%) <130 mg/dL >160 mg/dL Lower risk: 0-1 risk factor* <160 mg/dL 160 mg/dL >190 mg/dL ( mg/dL: LDL-lowering drug optional) Having 0 to 1 risk factors is considered low risk. A risk score less than 10% in those with 2 or more risk factors is considered moderate risk. A score between 10% and 20% is considered moderately high risk, and high risk is greater than 20%. For people in the high risk category, the goal is to reduce the LDL cholesterol levels to below 100 mg/dL, with an optional LDL target of < 70 mg/dL. High-risk individuals with LDL cholesterol above 100 mg/dL will benefit from lifestyle changes as well as drug therapy options. Moderately high risk individuals have an LDL cholesterol goal of less than 130g/dL, above which drug therapy should be considered. Moderate risk individuals with an LDL cholesterol level below 130 mg/dl should make lifestyle modifications. In low risk persons, cholesterol-lowering medications should generally only be considered if LDL cholesterol is above 160 mg/dL. Medication may be considered in an individual has a family history of premature heart disease. Low risk individuals should strive for an LDL goal of less than 130 mg/dL which is about average for all adults. Individuals above this level should make lifestyle modifications to optimize risk factors. *Risk factors for cardiovascular disease include: cigarettes smoking, hypertension (blood pressure >140/90 mmHg or on antihypertensive medication, HDL-C <40 mg/dl (>60 mg/dl is a negative risk factor), family history of premature CHD, age >45 years in men or >55 years in women. ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol, TLC=Therapeutic lifestyle changes Grundy, S. et al. Circulation 2004;110:

Primary Therapies to Lower LDL-C
Class Drug(s) 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors [Statins] Atorvastatin (Lipitor) Fluvastatin (Lescol XL) Lovastatin (generic and Mevacor) Pravastatin (Pravachol) Rosuvastatin (Crestor) Simvastatin (Zocor) Bile acid sequestrants Cholestyramine (generic and Questran) Colesevelam (Welchol) Colestipol (Colestid) Cholesterol absorption inhibitor Ezetimibe (Zetia) Dietary Adjuncts Soluble fiber Soy protein Stanol esters There are several lipid-lowering medications available. Four classes of lipid lowering medications include. Statins are the most effective and most commonly prescribed class of drug for lowering LDL cholesterol. The statins available include atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin ( Zocor). These agents work by blocking the production of cholesterol in the liver. Bile acid sequestrants are another class of lipid-lowering medication. These drugs function by binding bile acids in the intestine and eliminating them in the stool. They are often taken alone but are more effective in combination with a statin or niacin, a B vitamin. Cholesterol absorption inhibitors work by blocking the absorption of cholesterol from the small intestine, including cholesterol from food as well as cholesterol in bile acids. Dietary supplements such as soluble fiber, soy protein, and stanol esters are also effective in helping to lower cholesterol.

HMG-CoA Reductase Inhibitor: Dose-Dependent Effect
The Rule of 6’s In general, each doubling of the dose of a statin drug produces approximately a 6% decrease in LDL cholesterol. The potency of the statin drugs varies, with fluvastatin being the least potent and atorvastatin and rosuvastatin being the most potent of the currently available drugs. However, there can be significant variability to which a given statin may lower LDL cholesterol. The effect of the statins on LDL cholesterol is dose-related. At the lowest starting dose of each statin, the mean reduction in LDL cholesterol is approximately 20% to 40%. Thereafter, a doubling of the dose of the statin drug lowers LDL-C approximately another 6%. Titration to the maximum approved dose produces a mean reduction of approximately 31% to 51%. Illingworth DR. Med Clin North Am. 2000;84:23-42 Each doubling of the statin dose produces an additional 6% reduction in the LDL-C level Illingworth DR. Med Clin North Am. 2000;84:23-42.

HMG-CoA Reductase Inhibitor: Primary Prevention
West of Scotland Coronary Prevention Study (WOSCOPS) 6,595 men with moderate hypercholesterolemia randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels 31% RRR 9 7.5 6 5.3 Rate of MI or CHD death (%) 3 P<0.001 The West of Scotland Coronary Prevention Study (WOSCOPS) found that pravastatin significantly reduced the rate of MI or death from coronary heart disease in men with average cholesterol levels. Total coronary events, however, fell from ~10% to 7% over a 5 year period. Placebo Pravastatin CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction Shepherd J et al. NEJM 1995;333:

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) 6,605 patients with average LDL-C levels randomized to lovastatin (20-40 mg) or placebo for 5.2 years Statins provide significant benefit in those with average LDL-C levels 37% RRR 6 5.5 4 Rate of MI, unstable angina, or SCD (%) 3.5 2 In the AFCAPS/TexCAPS study, statins lowered the risk of a future CHD event in asymptomatic women and men if their HDL-Cholesterol was below average. P<0.001 Placebo Lovastatin MI=Myocardial infarction, RRR=Relative risk reduction, SCD=Sudden cardiac death Downs JR et al. JAMA 1998;279(20):1615–1622

Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) 10,305 patients with hypertension randomized to atorvastatin (10 mg) or placebo for 5 years Statins provide significant benefit in moderate- to high-risk individuals by lowering LDL-C levels below current goals 4 Atorvastatin 90 mg/dl* Placebo mg/dl* 3 36% RRR Cumulative incidence of MI and fatal CHD (%) 2 1 P=0.0005 The Anglo-Scandinavian Cardiac Outcomes Trial demonstrated that people with hypertension and average lipids benefited from a statin. Indviduals taking the statin experienced a lower cumulative incidence of heart attack and cardiovascular-related death than people taking the placebo. 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Follow-up (yr) CHD=Coronary heart disease, RR=Relative risk *Post-treatment LDL-C level Sever PS et al. Lancet. 2003;361:

HMG-CoA Reductase Inhibitor: Secondary Prevention
Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Trial (MIRACL) 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate 17.4% 5 10 15 Atorvastatin Placebo 14.8% Combined cardiovascular event rate (%)* RR=0.84, P=0.048 The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Trial (MIRACL) showed that acute treatment with a high dose of a statin lowers cardiac risk in individuals with an acute coronary syndrome (unstable coronary event). 4 8 12 16 Weeks *Includes death, myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. Schwartz GG et al. JAMA 2001;285:

Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate 30 Atorvastatin Pravastatin 16% RRR 25 20 Recurrent MI or Cardiac Death 15 10 5 P =0.005 The Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study demonstrated that high dose lipid-lowering therapy benefits persons with an acute heart attack or those with unstable angina more so than a moderate dose of a statin. Follow-up (months) ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:

Scandinavian Simvastatin Survival Study (4S) 4,444 patients with angina pectoris or previous MI randomized to simvastatin (20-40 mg) or placebo for 5.4 years Statins provide significant benefit in those with average LDL-C levels 30% RRR 11.5 12 8.2 8 Mortality (%) 4 The Scandinavian Simvastatin Survival Study (4S) was a landmark study that evaluated the effect of a statin in the secondary prevention of a cardiovascular event. The study demonstrated that simvastatin reduced mortality in high risk people. While the placebo group experienced an 11.5% mortality rate, the simvastatin group experienced an 8.2% mortality rate. P<0.001 Placebo Simvastatin MI=Myocardial infarction, RRR=Relative risk reduction 4S Group. Lancet 1994;344:1383–1389

Cholesterol and Recurrent Events (CARE) Study 4,159 patients with a history of MI randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels 24% RRR 15 13.2 10.2 10 Rate of MI or CHD death (%) 5 P=0.003 The Cholesterol and Recurrent Events (CARE) trial demonstrated that pravastatin decreased the rate of cardiovascular-related death or heart attack in people with a history of a heart attack and average lipid levels from ~13% to 10%. Placebo Pravastatin CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction Sacks FM et al. NEJM 1996;335:1001–1009

Heart Protection Study (HPS) 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 years Statins provide significant benefit across a broad range of LDL-C levels Event Rate Ratio (95% CI) Baseline LDL-C (mg/dL) Statin (n = 10,269) Placebo (n = 10,267) <100 282 (16.4%) 358 (21.0%) 100–129 668 (18.9%) 871 (24.7%) 130 1083 (21.6%) 1356 (26.9%) All patients 2033 (19.8%) 2585 (25.2%) Statin Better Statin Worse 0.76 (0.72–0.81) P<0.0001 The Heart Protection Study (HPS) showed that simvastatin benefited people regardless of their baseline lipid levels. The trial found that treatment with simvastatin resulted in a 12% relative risk reduction in mortality and a 24% relative risk reduction in the first occurrence of any major vascular event. In persons with a baseline normal LDL-cholesterol of <100 mg/dl, simvastatin lowered the event rate from 21% to 16%. 0.4 0.6 0.8 1.0 1.2 1.4 CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22

HMG-CoA Reductase Inhibitor: Dose-Dependent Effect
The Rule of 6’s In general, each doubling of the dose of a statin drug produces approximately a 6% decrease in LDL cholesterol. The potency of the statin drugs varies, with fluvastatin being the least potent and atorvastatin and rosuvastatin being the most potent of the currently available drugs. However, there can be significant variability to which a given statin may lower LDL cholesterol. The effect of the statins on LDL cholesterol is dose-related. At the lowest starting dose of each statin, the mean reduction in LDL cholesterol is approximately 20% to 40%. Thereafter, a doubling of the dose of the statin drug lowers LDL-C approximately another 6%. Titration to the maximum approved dose produces a mean reduction of approximately 31% to 51%. Illingworth DR. Med Clin North Am. 2000;84:23-42 Each doubling of the statin dose produces an additional 6% reduction in the LDL-C level Illingworth DR. Med Clin North Am. 2000;84:23-42.

West of Scotland Coronary Prevention Study (WOSCOPS) 6,595 men with moderate hypercholesterolemia randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels 31% RRR 9 7.5 6 5.3 Rate of MI or CHD death (%) 3 P<0.001 The West of Scotland Coronary Prevention Study (WOSCOPS) found that pravastatin significantly reduced the rate of MI or death from coronary heart disease in men with average cholesterol levels. Total coronary events, however, fell from ~10% to 7% over a 5 year period. Placebo Pravastatin CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction Shepherd J et al. NEJM 1995;333:

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) 6,605 patients with average LDL-C levels randomized to lovastatin (20-40 mg) or placebo for 5.2 years Statins provide significant benefit in those with average LDL-C levels 37% RRR 6 5.5 4 Rate of MI, unstable angina, or SCD (%) 3.5 2 In the AFCAPS/TexCAPS study, statins lowered the risk of a future CHD event in asymptomatic women and men if their HDL-Cholesterol was below average. P<0.001 Placebo Lovastatin MI=Myocardial infarction, RRR=Relative risk reduction, SCD=Sudden cardiac death Downs JR et al. JAMA 1998;279(20):1615–1622

Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) 10,305 patients with hypertension randomized to atorvastatin (10 mg) or placebo for 5 years Statins provide significant benefit in moderate- to high-risk individuals by lowering LDL-C levels below current goals 4 Atorvastatin 90 mg/dl* Placebo mg/dl* 3 36% RRR Cumulative incidence of MI and fatal CHD (%) 2 1 P=0.0005 The Anglo-Scandinavian Cardiac Outcomes Trial demonstrated that people with hypertension and average lipids benefited from a statin. Indviduals taking the statin experienced a lower cumulative incidence of heart attack and cardiovascular-related death than people taking the placebo. 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Follow-up (yr) CHD=Coronary heart disease, RR=Relative risk *Post-treatment LDL-C level Sever PS et al. Lancet. 2003;361:

Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Trial (MIRACL) 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate 17.4% 5 10 15 Atorvastatin Placebo 14.8% Combined cardiovascular event rate (%)* RR=0.84, P=0.048 The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Trial (MIRACL) showed that acute treatment with a high dose of a statin lowers cardiac risk in individuals with an acute coronary syndrome (unstable coronary event). 4 8 12 16 Weeks *Includes death, myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. Schwartz GG et al. JAMA 2001;285:

Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate 30 Atorvastatin Pravastatin 16% RRR 25 20 Recurrent MI or Cardiac Death 15 10 5 P =0.005 The Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study demonstrated that high dose lipid-lowering therapy benefits persons with an acute heart attack or those with unstable angina more so than a moderate dose of a statin. Follow-up (months) ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:

Scandinavian Simvastatin Survival Study (4S) 4,444 patients with angina pectoris or previous MI randomized to simvastatin (20-40 mg) or placebo for 5.4 years Statins provide significant benefit in those with average LDL-C levels 30% RRR 11.5 12 8.2 8 Mortality (%) 4 The Scandinavian Simvastatin Survival Study (4S) was a landmark study that evaluated the effect of a statin in the secondary prevention of a cardiovascular event. The study demonstrated that simvastatin reduced mortality in high risk people. While the placebo group experienced an 11.5% mortality rate, the simvastatin group experienced an 8.2% mortality rate. P<0.001 Placebo Simvastatin MI=Myocardial infarction, RRR=Relative risk reduction 4S Group. Lancet 1994;344:1383–1389

Cholesterol and Recurrent Events (CARE) Study 4,159 patients with a history of MI randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels 24% RRR 15 13.2 10.2 10 Rate of MI or CHD death (%) 5 P=0.003 The Cholesterol and Recurrent Events (CARE) trial demonstrated that pravastatin decreased the rate of cardiovascular-related death or heart attack in people with a history of a heart attack and average lipid levels from ~13% to 10%. Placebo Pravastatin CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction Sacks FM et al. NEJM 1996;335:1001–1009

Heart Protection Study (HPS) 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 years Statins provide significant benefit across a broad range of LDL-C levels Event Rate Ratio (95% CI) Baseline LDL-C (mg/dL) Statin (n = 10,269) Placebo (n = 10,267) <100 282 (16.4%) 358 (21.0%) 100–129 668 (18.9%) 871 (24.7%) 130 1083 (21.6%) 1356 (26.9%) All patients 2033 (19.8%) 2585 (25.2%) Statin Better Statin Worse 0.76 (0.72–0.81) P<0.0001 The Heart Protection Study (HPS) showed that simvastatin benefited people regardless of their baseline lipid levels. The trial found that treatment with simvastatin resulted in a 12% relative risk reduction in mortality and a 24% relative risk reduction in the first occurrence of any major vascular event. In persons with a baseline normal LDL-cholesterol of <100 mg/dl, simvastatin lowered the event rate from 21% to 16%. 0.4 0.6 0.8 1.0 1.2 1.4 CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22

Nicotinic Acid: Efficacy at Raising HDL-C
30% 30% HDL-C 26% 22% 15% 10% –9% Change from Baseline –14% –5% –17% –21% –22% LDL-C –11% –28% Niacin Niacin (also called nicotinic acid) are the most effective medication for raising HDL cholesterol levels. Niacin raises HDL cholesterol by 15-30% and can also lower triglyceride levels by 20-30%. Niacin is most commonly available in two prescription forms: immediate release (Niacor) and extended release (Niaspan). A major disadvantage of niacin (particularly in the immediate release form) are the side effects such as skin flushing and itching. More serious, but less common side effects with high dose niacin include elevated liver function blood tests, peptic ulcer development and a rise in blood glucose and uric acid levels. –35% TG –39% –44% Dose (mg) 500 1000 1500 2000 2500 3000 Goldberg A et al. Am J Cardiol 2000;85:

Fibrate: Primary and Secondary Prevention
42% Rx Placebo 22% 22.3 21.7*** 9% 17.3 15.0 13.6 % CHD Death/Nonfatal MI 66% 13.0 34% 8.0 4.1*** 2.7 2.7 HHS HHS* BIP BIP** VA-HIT Fibrates Fibrates are the most effective lipid lowering medication for people with elevated blood triglyceride levels (> 200 mg/dl ), particularly when the HDL cholesterol is low. Because fibrates may cause increases in LDL cholesterol levels, they may be prescribed in conjunction with a statin. A fibrate is often added to statin therapy when triglyceride levels remain above normal while taking a statin. Fibrates work by stimulating the activity of an enzyme called lipoprotein lipase that breaks down trigylcerides. PRIMARY PREVENTION SECONDARY PREVENTION *Post hoc analysis of subgroup with TG >200 mg/dL and HDL-C <42 mg/dL. **Post hoc analysis of subgroup with TG 200 mg/dL and HDL-C <35 mg/dL. ***Difference between placebo and Rx for primary endpoint was statistically significant (p < 0.05). Frick MH et al. NEJM 1987;317: Manninen V et al. Circulation 1992;85:37-45 BIP Study Group. Circulation 2000;102:21-27 Rubins HB et al. NEJM 1999;341:

Cigarette Smoking Cessation Guidelines
Goals Recommendations Complete cessation No environmental tobacco smoke exposure Ask about tobacco use at every visit. In a clear, strong, and personalized manner, advise the patient to stop smoking. Urge avoidance of exposure to secondhand smoke at work and home. Assess the patient’s willingness to quit smoking. Develop a plan for smoking cessation and arrange follow-up. Provide counseling, pharmacologic therapy, and referral to formal smoking cessation programs as indicated. Smoking Cessation Quitting smoking is one of the most effective lifestyle changes to prevent CHD. Smoking is a difficult habit to break. Only about 5-10% of people successfully quit on their own, without any kind of aid or reinforcement. A combination of counseling, drug therapy, and nicotine replacement therapy is most effective for cigarette smoking cessation. Combining all three options increases the likelihood of quitting to about 35%.

Smoking Cessation Pharmacotherapy*
Agent Caution Side Effects Dosage Duration Instructions Bupropion SR (Zyban®) Seizure disorder Eating disorder Taking MAO inhibitor Pregnancy Insomnia Dry mouth 150 mg QAM then 150 mg BID 3 days Maintenance (8 weeks, but may be used up to 6 months) Start 1-2 weeks before quit date. Take second dose in early afternoon or decrease to 150 mg QAM for insomnia. Transdermal Nicotine Patch** Within 2 weeks of a MI Unstable angina Arrhythmias Decompensated heart failure Skin reaction 21 mg QAM 14 mg QAM 7 mg QAM or 15 mg QAM 4 weeks 2 weeks 8 weeks Apply to different hairless site daily. Remove before bed for insomnia. Start at <15 mg for <10 cigs/day There are many treatment options for smoking cessation. Bupoprion (Zyban), nicotine replacement therapy, and varenicline (Chantix) are drugs that are available and effective to help with smoking cessation. Bupropion is a prescription antidepressant that helps reduce cravings and withdrawal symptoms. People usually take the drug one to two weeks before their quit date and continue taking it for two months. Nicotine replacement therapy comes in several form including gum, a skin patch, nasal spray, inhaler, and lozenge. Nicotine replacement therapy works by releasing small amounts of nicotine into the bloodstream, which helps to reduce withdrawal symptoms and control cravings. These therapies are usually taken for two to eight weeks. Varenicline is a newer medication that may be more effective than Zyban. Varenicline acts on nicotine receptors in the brain, reducing cravings and withdrawal symptoms. People begin taking Varenicline one week before their quit date and continue taking it for the next 12 weeks. Counseling sessions – either individual or group – in addition to drug therapy often provides the best success rate for quitting smoking. During these sessions, people learn coping mechanisms, relapse prevention, and stress management. *Pharmacotherapy combined with behavioral support provides the best success rate **Other nicotine replacement therapy options include: nicotine gum, lozenge, inhaler, nasal spray

Cigarette Smoking Cessation: Primary Prevention
893 smokers randomized to 9 weeks of buproprion (150 mg a day for 3 days and then 150 mg twice daily), NRT (21 mg patch weeks 2-7, 14 mg patch week 8, and 7 mg patch week 9), bupropion and NRT, or placebo Bupropion with or without NRT provides the greatest benefit Placebo (n=160) NRT (n=244) Bupropion (n=244) Nicotine patch and Bupropion (n=245) Abstinence rate at 6 months 18.8% 21.3% 34.8%a,b 38.8%a,c,d Abstinence rate at 12 months 15.6% 16.4% 30.3%a,c 35.5%a,c,e This trial compared nicotine replacement therapy to buproprion and to a combination of buproprion/nicotine replacement therapy and placebo. It found that buproprion with or without nicotine replacement therapy provides the greatest benefit and is associated with smoking cessation rates of more than 30%. NRT=Nicotine replacement therapy ap<0.001 when compared to placebo bp=0.001 when compared to NRT cp<0.001 when compared to NRT dp=0.37 when compared to buproprion ep=0.22 when compared to buproprion Jorenby DE et al. NEJM 1999;340:685-91

Smoking Cessation Pharmacotherapy: Varenicline
Study 1 p<0.001 for V vs B p<0.001 for V vs P Study 2 Two trials compared treatment with varenicline, a nicotine acetylcholine receptor agonist, to treatment with buproprion or placebo. These trials included a total of almost 700 participants. The mean duration of smoking was 25 years. Varenicline yielded higher rates of smoking cessation than buproprion or placebo. Varenicline (Chantix) is a newer medication that may be more effective than buproprion. Two trials randomized long-term smokers (mean duration of smoking 25 years) to varenicline (1 mg twice daily), buproprion (150 mg twice daily) or placebo for 12 weeks. In both trials, treatment with varenicline was associated with higher rates of smoking cessation than buproprion or placebo. JAMA 2006:296:47-55 and JAMA 2006;296:56-63

Weight Management Guidelines
Goals Recommendations Calculate BMI* and measure waist circumference as part of evaluation. Monitor response of BMI and waist circumference to therapy. BMI 18.5 to 24.9 kg/m2 Women: <35 inches Men: <40 inches Start weight management and physical activity as appropriate. If BMI and/or waist circumference is above goal, initiate caloric restriction, measures to increase caloric expenditure, and treatment strategies for the metabolic syndrome. 10% weight reduction within the first year of therapy Weight Management Obesity is a major risk factor for cardiovascular disease. Body mass index (BMI), a measurement of weight in relation to height, is used to determine if someone has less than ideal weight, normal weight, an overweight state, or obesity. BMI is calculated by multiplying a person’s weight in pounds by 703, and then dividing the result by the square of their height in inches. The goal BMI is 18.5 to 24.9 kg/m2. A BMI of kg/m2 is considered overweight, and >30 kg/m2 is considered obese. The effect of obesity on the development of cardiovascular disease depends not only on total amount of body fat, but also on the distribution of body fat. Excess weight concentrated in the abdomen is particularly problematic because it leads to insulin resistance, a reduced ability of the body to respond to insulin. Insulin is a hormone secreted by the pancreas that helps the body use glucose as a source of energy. People with insulin resistance are more likely to develop diabetes and often have high triglyceride levels, low levels of HDL cholesterol, and high blood pressure. When a low-fat diet is combined with regular exercise, there is an excellent chance of losing weight and maintaining that weight loss long term. A healthy rate of weight loss is lbs a week. BMI=Body mass index *BMI is calculated as the weight in kilograms divided by the body surface area in meters2. Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2.

Prevalence of Obesity in U.S. Adults
1991 1996 2003 Americans are becoming increasingly more obese. An estimated 65% of adults in the United States are either overweight or obese. % State Population No Data <10% %–14% %–19% %–24% ≥25% Source: CDC Overweight and Obesity

CV Risk Increases with Body Mass Index
0.5 1.0 2.0 4.0 16 20 24 28 32 36 Body Mass Index (kg/m2)* Hazard Ratio Hemorrhagic Stroke Ischemic Stroke Ischemic Heart Disease This study from the Asia-Pacific region found that a higher BMI is associated with higher cardiovascular risk. CV=Cardiovascular Body mass index is calculated as the weight in kilograms divided by the body surface area in meters2. Mhurchu N et al. Int J Epidemiol 2004;33:

Diabetes Mellitus Guidelines
Goals Recommendations Intensive lifestyle modification to prevent the development of DM (especially in those with the metabolic syndrome) Aggressive management of CV risk factors (i.e., tobacco use, hypertension, dyslipidemia, physical inactivity, and overweight and obese states) Hypoglycemic therapy to achieve normal to near normal fasting plasma glucose as defined by the HbA1C (<7%) Weight reduction and exercise Oral hypoglycemic agents Insulin therapy Coordination of diabetic care with the patient’s primary physician and/or endocrinologist. Goal HbA1C <7% Diabetes Mellitus People with diabetes are two to four times more likely to develop CHD than those without diabetes. Risk factors for CHD, such as elevated triglycerides, low HDL cholesterol, high blood pressure, and obesity, are more prevalent in people with diabetes. Diabetes itself also increases the risk of CHD. Individuals diagnosed with prediabetes, in which blood glucose levels are elevated (between 100 and 125 mg/dL on a fasting blood test), are also at a higher risk for CHD. If someone has diabetes or prediabetes, it is important to make aggressive lifestyle changes to control other CHD risk factors. According to the latest NCEP guidelines, people with diabetes should lower their LDL cholesterol to less than 100mg/dL (and preferably to less than 70mg/dL) and should have a blood pressure below 130/80 mmHg. CV=Cardiovascular, DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin

The Metabolic Syndrome
Consists of a constellation of major risk factors, life-habit risk factors, and emerging risk factors Over-represented among populations with cardiovascular disease Often occurs in individuals with a distinctive body-type including an increased abdominal circumference Metabolic Syndrome The metabolic syndrome is a constellation of cardiovascular risk factors. It usually occurs in people with a distinctive body type that includes increased abdominal circumference. Each of the risk factors that make up the metabolic syndrome can predispose to endothelial dysfunction (damage the walls of blood vessels) leading to increased risk of cardiovascular disease, diabetes, and stroke. Thus, those with the metabolic syndrome are at increased risk for cardiovascular disease and events, as well as diabetes and stroke. The most effective treatment is lifestyle alterations including increased exercise and weight loss. Drug therapy to lower cholesterol levels, triglyceride levels, blood pressure and blood glucose levels can also be effective as well.

ATP III Definition of the Metabolic Syndrome
Defined by presence of >3 risk factors Risk Factor Defining Level Waist circumference (abdominal obesity) >40 in (>102 cm) in men >35 in (>88 cm) in women Triglyceride level >150 mg/dl HDL-C level <40 mg/dl in men <50 mg/dl in women Blood pressure >130/>85 mmHg Fasting glucose >100 mg/dl The metabolic syndrome is defined by the presence of at least three of the following characteristics: Excess fat around the abdomen (a waist circumference greater than 40 inches in men or 35 inches in women) Elevated triglycerides (>150 mg/dL) , low HDL-C (< 40 mg/dl in men or < 50 mg/dl in women), High blood pressure (>130/>85mmHg) or taking blood pressure-lowering medication An elevated fasting blood glucose level (100mg/dL or higher) HDL-C=High-density lipoprotein cholesterol Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:

Metabolic Syndrome: Risk of Developing DM
Finnish Diabetes Prevention Study 522 overweight (mean BMI=31 kg/m2) patients with impaired fasting glucose† randomized to intervention‡ or usual care for 3.2 years Lifestyle modification reduces the risk of developing DM Intervention Control 23% 11% The Finnish Diabetes Prevention Study examined the effectiveness of lifestyle modifications in reducing the development of type 2 diabetes in middle-aged adults at high risk for diabetes (with impaired fasting glucose). The study found that that changes in lifestyle can significantly reduce the development of type 2 diabetes. In the study, lifestyle intervention included increased physical activity, modest weight loss, and a better diet. After 3.2 years, the lifestyle intervention group had more than a 50% reduction in the development of diabetes. % with Diabetes Mellitus †Defined as a glucose >140 mg/dl 2 hours after an oral glucose challenge ‡Aimed at reducing weight (>5%), total intake of fat (<30% total calories) and saturated fat (<10% total calories); increasing uptake of fiber (>15 g/1000 cal); and physical activity (moderate at least 30 min/day) Tuomilehto J et al. NEJM 2001;344:

Metabolic Syndrome: Risk of Developing DM
Diabetes Prevention Program (DPP) 3,234 patients with elevated fasting and post-load glucose levels randomized to placebo, metformin (850 mg twice daily), or lifestyle modification* for 2.8 years Lifestyle modification reduces the risk of developing DM Placebo Metformin Lifestyle modification 40 30 Incidence of DM (%) 20 10 The Diabetes Prevention Program (DPP) trial compared the effect of lifestyle modifications (diet and exercise) to the oral diabetes drug metformin (Glucophage) and placebo in reducing the incidence of type 2 diabetes in individuals at high risk for diabetes. The DPP found that metformin and lifestyle modification both reduce the incidence of diabetes in people with impaired glucose tolerance. However, metformin reduced the risk of type two diabetes less drastically than did lifestyle modifications. 1 2 3 4 Years *Includes 7% weight loss and at least 150 minutes of physical activity per week Knowler WC et al. NEJM 2002;346:

Optimal: 30 minutes daily
Exercise Guidelines Goals Recommendations Assess risk, preferably with exercise test, to guide prescription. Encourage aerobic activity (e.g., walking, jogging, cycling) supplemented by an increase in daily activities (e.g., walking breaks at work, gardening, household work). Encourage resistance training (e.g., weight machines, free weights) 2 days a week (Class IIb, Level C) Encourage cardiac rehabilitation for patients with chronic stable angina, recent myocardial infarction, left ventricular systolic dysfunction, or recent coronary artery bypass graft surgery. Minimum: 30 minutes, 5 days per week Optimal: 30 minutes daily Exercise Regular physical activity helps to prevent CHD and prevent heart attacks in individuals who already have CHD. Regular exercise helps to control weight, lower blood pressure, improve blood lipid levels, and relieve stress. Exercise also helps the heart pump blood more efficiently and enhances the body’s response to insulin, which helps to prevent type 2 diabetes. The Centers for Disease Control and Prevention and the American College of Sports Medicine recommend that adults get 30 minutes or more of physical activity, 5 days a week. However, 30 minutes of daily exercise is optimal. This physical activity should be performed at a moderate intensity, equivalent to walking at a pace of three to four miles per hour. Examples of moderate-intense activities include walking up the stairs, walking, and riding a stationary bicycle. Gardening and housework can also count as part of the 30 minute total if they are performed at a moderate-high level intensity. This activity can be done in short 8-10 minute bursts, or all at once. In order to determine the amount and type of exercise appropriate for an individual, doctors will often recommend an exercise stress test to evaluate the heart’s response to work or physical exertion. A stress test helps to assess whether during physical activity, the heart is receiving enough blood, or if it develops an abnormal rhythm. An abnormal stress test may indicate that a narrowing or blockage exists in one of the arteries that supplies the heart with blood.

Ejection Fraction Guidelines
Secondary Prevention Echocardiography in those following a STEMI to re-evaluate ventricular function when results are used to guide therapy*. Echocardiography or radionuclide angiography in those following a NSTE-ACS when results are used to guide therapy*. I IIa IIb III C Ejection Fraction The ejection fraction is a measure of the quantity of blood ejected with each contraction of the heart. Knowledge of the ejection fraction may help to determine the appropriate treatments for individuals that have had a cardiovascular event. Echocardiography (a test that reveals the size and shape of the heart’s chambers, its activity, and the ejection fraction) or radionuclide angiography (a test that determines the location and extent of blockages in the coronary arteries) can be used to measure the ejection fraction in people who have had a heart attack. Certain medications are more apt to be prescribed if the heart muscle function is reduced. NSTE-ACS=Non-ST-segment elevation acute coronary syndrome, STEMI=ST-segment elevation myocardial infarction *Includes use of an aldosterone antagonist, digitalis, and/or an implantable cardioverter defibrillator

Digitalis: Recommendations
Secondary Prevention I IIa IIb III B Digitalis in those with symptomatic HF and LVSD (EF <45%) to reduce hospitalizations for HF*. Digitalis in those with asymptomatic LVSD and normal sinus rhythm. Heart failure is caused by a weakening of the heart’s ability to pump blood. The most common cause of heart failure is heart damage due to CHD or high blood pressure. A number of drugs are used to manage heart failure, including ACE inhibitors, diuretics, beta-blockers, and digitalis. Digitalis is a type of drug that may help to reduce hospitalizations for heart failure in patients with an ejection fraction <45%. EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function *Contraindications include significant sinus or atrioventricular block unless a permanent pacemaker is present.

Relationship Between EF* and Mortality
50 <30 40 30 Cardiac Mortality % 31-35 20 36-45 10 46-53 Mortality due to cardiac events increases dramatically once the heart muscle ejection fraction drops below 35%. 54-60 >60 80 70 60 50 40 30 20 Ejection Fraction (%) EF=Ejection fraction *Post myocardial infarction Brodie B et al. Am J Cardiol 1992;69:1113

Aldosterone Antagonist: Secondary Prevention
Randomized Aldactone Evaluation Study (RALES) 1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35) randomized to spironolactone (25 mg) or placebo (50 mg) for 24 months Aldosterone inhibition provides significant benefit in patients with advanced heart failure 1.00 Spironolactone Placebo .90 .80 Survival (%) .70 .60 .50 RR = 0.70, P<0.001 3 6 9 12 15 18 21 24 27 30 33 36 The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone (an aldosterone antagonist) is beneficial for patients with advanced heart failure. Spironolactone acts on the kidneys and and increases the elimination of water and sodium from the body in the urine. Blood tests to measure the potassium level and kidney function should be intermittently performed for people on an aldosterone antagonist. Months EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association Pitt B et al. NEJM 1999;341:

Aldosterone Antagonist: Secondary Prevention
Eplerenone Poct-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) 3,313 patients with evidence of heart failure and LVSD (EF <0.40) after a MI randomized to eplerenone (50 mg) or placebo for 16 months Aldosterone inhibition provides significant benefit in patients with post-MI heart failure and LVSD 6 12 18 24 30 36 5 10 15 20 25 Eplerenone Placebo All Cause Mortality (%) RR = 0.85, P=0.008 Eplerenone is another type of aldosterone antagonist that provides benefit to people with heart failure due to CHD. Eplerenone may be better tolerated than spironolactone by some men because of a reduced incidence of gynecomastia (the development of prominent breast tissue in males). Month EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Pitt B et al. NEJM 2003;348:

At least one month following a myocardial infarction
ICD Algorithm At least one month following a myocardial infarction EF < 30% EF 31-40% EF > 40% Additional Marker of Electrical Instability? Yes No No ICD. Medical Rx Implantable cardioverter-defibrillator (ICD) An ICD is a device that constantly monitors the heart’s rhythm. An ICD can stop a life-threatening ventricular arrhythmia. When it detects an arrhythmia, it delivers an electric shock that returns the heart to its normal rhythm. ICDs are often recommended for people who have had a heart attack and have an ejection fraction of <30%, as well as those with an ejection fraction of 31-40% and high-risk ventricular arrhythmias. EPS + - EF=Ejection fraction, EPS=Electrophysiology study, ICD=Implantable cardioverter defibrillator, Rx=Treatment, SCD=Sudden cardiac death, NEJM 349:1836,2003

ICD: Secondary Prevention* % Mortality Reduction w/ ICD Rx
Overall death 75% 73% Arrhythmic death 61% 55% 54% % Mortality Reduction w/ ICD Rx 31% ICDs greatly reduce the risk of sudden cardiac death in high risk patients. Three major clinical trials - the first Multicenter Automatic Defibrillator Implantation Trial (MADIT), the second Multicenter Automatic Defibrillator Implantation Trial (MADIT II), and the Multicenter Unsustained Tachycardia Trial (MUSTT) - concluded that patients at high risk of cardiovascular events benefited from the implantation of an ICD. 1 2 3 27 Months 39 Months 20 Months EF <35% EF <40% EF <30% *Primary prevention of sudden cardiac death 1 Moss AJ. N Engl J Med. 1996;335: 2 Buxton AE. N Engl J Med. 1999;341: 3 Moss AF. N Engl J Med. 2002;346:

Familial predisposition
Prevention Pyramid Physical activity Healthy eating Ideal weight Psychosocial factors Familial predisposition Lipids Hypertension Smoking cessation Diabetes +Primordial ASA ACE-I Rehab β-blockers +Primary Secondary Primary The NCEP ATP III guidelines for therapeutic lifestyle changes (TLC) support the emerging concept of primordial prevention, which refers to strategies designed to prevent risk factors from actually becoming risk factors in the first place. These strategies, which focus on physical activity, diet, and weight loss, enable us to better deal with these risk factors and prevent the development of diseases such as dyslipidemia, hypertension, and diabetes. Primordial ACE-1 = angiotensin converting enzyme inhibitor; ASA = aspirin

The ABC’s of the AHA/ACC Prevention Guidelines

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The ABC’s of the AHA/ACC Prevention Guidelines

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