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Heart Disease in Women: New Concepts in Prevention and Management Nathan D. Wong, PhD, FACC Professor and Director Heart Disease Prevention Program Division.

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Presentation on theme: "Heart Disease in Women: New Concepts in Prevention and Management Nathan D. Wong, PhD, FACC Professor and Director Heart Disease Prevention Program Division."— Presentation transcript:

1 Heart Disease in Women: New Concepts in Prevention and Management Nathan D. Wong, PhD, FACC Professor and Director Heart Disease Prevention Program Division of Cardiology University of California, Irvine

2 Heart Disease The leading killer of women at all ages

3 So how long have we known that women are just not small men???

4 Cardiovascular Disease in Women 38.2 million women (34%) are living with cardiovascular disease and a much larger population is at risk.38.2 million women (34%) are living with cardiovascular disease and a much larger population is at risk. Heart disease and stroke are the no. 1 and no. 3 killers of women over age 25Heart disease and stroke are the no. 1 and no. 3 killers of women over age 25 1 in 30 die of breast cancer, but 1 in 2.5 die of cardiovascular disease or stroke.1 in 30 die of breast cancer, but 1 in 2.5 die of cardiovascular disease or stroke. 66,000 more women than men die per year of cardiovascular disease; represents 54% of deaths in women compared to 46% in men.66,000 more women than men die per year of cardiovascular disease; represents 54% of deaths in women compared to 46% in men. AHA Heart Disease and Stroke Statistics 2004 Update, and Mosca et al., Circulation 2007; 115:

5 CHD: Differences in Presentation and Findings in Women Compared to Men –Lower prevalence of MI –More severe CHF –More severe angina –Less angiographic CAD –More ostial lesions –More microvascular dysfunction? –Abnormal vasomotor tone? –More endothelial dysfunction? Source: Jacobs 2003

6 Diagnosis of Coronary Artery Disease in Women Chest pain is experienced by most women with CHD, but non-chest pain presentations are more common in women than men Other Presenting Symptoms –Upper abdominal pain, fullness, burning sensation –Shortness of breath –Nausea –Neck, back, jaw pain Associations –Precipitated by exertion –Precipitated by emotional distress Source: Charney 2002, Goldberg 1998

7 Women have smaller coronary arteries After correcting for body surface area, womens’ arteries are smallerAfter correcting for body surface area, womens’ arteries are smaller This can seriously affect symptoms from anything that reduces diameterThis can seriously affect symptoms from anything that reduces diameter –Stenosis –Endothelial dysfunction Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: Endo- thelium Smaller arteries

8 Plaque Erosion and Outward (Positive) Remodeling Plaque erosion and thrombus formation 2x likely in women (men have more plaque rupture)Plaque erosion and thrombus formation 2x likely in women (men have more plaque rupture) Outward (positive) remodeling- atherosclerotic lesion protrudes outward than impinging on the lumenOutward (positive) remodeling- atherosclerotic lesion protrudes outward than impinging on the lumen Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: Thrombus Formation Lumen Plaque erosion

9 Women suffer more plaque erosions (above) compared to plaque explosions in men (below), leading to more acute coronary syndromes (unstable angina) and non-Q MI in women, making diagnosis more difficult and leading to delays in treatment. Gender Differences in Atherosclerosis NEJM 1999

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11 NIH-NHLBI-sponsored Women’s Ischemia Syndrome Evaluation WISE About 50% of women sent home with “normal coronaries” continue to experience disabling symptomsAbout 50% of women sent home with “normal coronaries” continue to experience disabling symptoms Possibly d/t coronary microvascular or macrovascular endothelial dysfunctionPossibly d/t coronary microvascular or macrovascular endothelial dysfunction 673/936 enrolled in WISE had persistent chest pain (PChP)673/936 enrolled in WISE had persistent chest pain (PChP) PChP-w no obstructive disease is not a benign conditionPChP-w no obstructive disease is not a benign condition –2x the number of CV events (MIs, strokes,CHF and CV deaths) than those w/o PChP. –Johnson,D, etal EurHeart Journal 2006

12 Assessing Ischemic Disease Stress EKG may be less useful in looking for ischemiaStress EKG may be less useful in looking for ischemia –Guidelines still support for women with normal resting 12 lead EKG Decreased functional capacity may predict poor outcomesDecreased functional capacity may predict poor outcomes –WISE showed that women who could not achieve 4.7 METS of work had a risk of death or nonfatal MI 3.7x higher that others with better functional capacity Stress ECHO and SPECT are good options in womenStress ECHO and SPECT are good options in women

13 Mortality Rates in Women At Every Age, More Women Die From Heart Disease Than From Cancer National Center for Health Statistics. 1999: Coronary artery disease Stroke Lung cancer Breast cancer Colon cancer Endometrial cancer Age (years) Mortality Rate per 100, –49 50–54 55–59 60–64 65–69 70–74 75–79 80– % of women (1 in 2) will die from CVD compared with 4% (1 in 25) who will die from breast cancer

14 Women Experience Menopause….. Changes with MenopauseChanges with Menopause LipidsLipids Total-Cholesterol  Total-Cholesterol  HDL-Cholesterol HDL-Cholesterol  Prevalence DifferencesPrevalence Differences Hypertension  Hypertension  Metabolic Syndrome  Metabolic Syndrome  Risk Factor, Disease, or Outcome RiskRisk Factor, Disease, or Outcome Risk Triglycerides  Diabetes Mellitus  Triglycerides  Diabetes Mellitus  Obesity (BMI >30)***  Obesity (BMI >30)***  Waist Circumference >35”  Waist Circumference >35”  –***Obesity ~25% of women - BMI >30, Less leisure-time physical activity - Greater functional decline - Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74:

15 Menopause and the Risk of Coronary Heart Disease (modified data from “Menopausal status as a risk for coronary artery disease” Arch Intern Med 1995;155:57-61 Age (in years) Annual Occurence of Heart Attack/1000

16 Chest pain or Angina Chest pain or Angina Typical Angina: heaviness, pressure or squeezing sensation behind the breastbone heaviness, pressure or squeezing sensation behind the breastbone with with radiation across the chest, up the neck or down the left arm radiation across the chest, up the neck or down the left arm or “strangling” or “suffocating” sensation. or “strangling” or “suffocating” sensation. caused or worsened by exercise and eased by rest caused or worsened by exercise and eased by rest usually lasts two to five minutes usually lasts two to five minutes Atypical Angina (frequently encountered in women): shortness of breath extreme fatigue lightheadedness or fainting nausea and/or indigestion

17 Women’s Early Warning Signs of a Heart Attack Weeks before Heart Attack (95% of women)Weeks before Heart Attack (95% of women)  Unusual fatigue (70.7%)  Sleep disturbance (47.8%)  Shortness of breath (42.1%)  Indigestion (39.4%)  Chest pain (29.7 %) At time of Heart AttackAt time of Heart Attack  Shortness of breath (57.9%)  Weakness (54.8%)  Fatigue (42.9%)  Chest pain (57%) McSweeney, JC et al. Circulation 2003;

18 Tracking women's awareness of heart disease: an American Heart Association national study Mosca L, et al. Circulation Feb 10;109(5):573-9 Telephone survey of a nationally representative random sample of women; 1024 respondents age > or =25 years 46% identified heart disease as the leading cause of death in women, up from 30% in 1997 and 34% in 2000 Black, Hispanic, and younger women (<45 years old) had lower awareness of heart disease Only 38% of women reported that their doctors had ever discussed heart disease with them.

19 Major Risk Factors Cigarette smoking (passive smoking?) Elevated total or LDL-cholesterol Hypertension (BP  140/90 mmHg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dL) † Family history of premature CHD –CHD in male first degree relative <55 years –CHD in female first degree relative <65 years Age (men  45 years; women  55 years) † HDL cholesterol  60 mg/dL counts as a “negative” risk factor; its presence removes one risk factor from the total count.

20 Other Recognized Risk Factors Obesity: Body Mass Index (BMI) –Weight (kg)/height (m 2 ) –Weight (lb)/height (in 2 ) x 703 Obesity BMI >30 kg/m 2 with overweight defined as 25-<30 kg/m 2 Abdominal obesity involves waist circumference >40 in. in men, >35 in. in women Physical inactivity: most experts recommend at least 30 minutes moderate activity at least 4-5 days/week

21 BMI and Relative Risk of CHD Over 14 Years: Nurse’s Health Study Relative risk of CHD increases for BMI > 23, diabetes risk increases for BMI > 22. Risk also significantly increases for weight gain after age 18 years of 5 kg or more.

22 Diabetes as a CHD Risk Equivalent 10-year risk for CHD  20% High mortality with established CHD –High mortality with acute MI –High mortality post acute MI Prevalence has increased over 25% in past 15 years in California, paralleling 50% increase in overweight/obesity

23 Probability of Death From CHD in Patients With NIDDM and in Nondiabetic Patients, With and Without Prior MI Kaplan-Meier estimates Haffner SM et al. N Engl J Med 1998;339:229– Nondiabetic subjects without prior MI Diabetic subjects without prior MI Nondiabetic subjects with prior MI Diabetic subjects with prior MI Years Survival (%)

24 Framingham Heart Study 30-Year Follow-Up: CVD Events in Patients With Diabetes (Ages 35-64) * Age-adjusted annual rate/1,000 MenWomen Total CVD CHDCardiac failure Intermittent claudication Stroke Risk ratio P<0.001 for all values except *P<0.05. Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease. Ruderman N et al, eds. Oxford; 1992.

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26 Adapted from Ballantyne CM. Am J Cardiol. 1998;82:3Q-12Q. Primary and Secondary Prevention Trials With Statins 2° prevention placebo 2° prevention statin 1° prevention placebo 1° prevention statin LDL-C Achieved (mg/dL) AFCAPS WOSCOPS CARE LIPID 4S Event Rate (%) HPS

27 CHD Events: Results of Secondary Prevention Studies in Women P value for heterogeneity=.35 Walsh et al. JAMA. 2004;291: Placebo No. Events/Women Intervention No. Events/Women RR (95% CI) 4S91/42060/ ( ) CARE80/29046/ ( ) LIPID104/76090/ ( ) HPS282/ / ( ) Total and summary 557/ / ( )

28 Testing for Ischemic Heart Disease in Women and Factors to Consider TechniqueAssessmentIssues in Women AngiographyCoronary anatomy Less focal disease Coronary CTCoronary calcification Less well-validated than other techniques Echocardiograp hy Regional wall motion Reader expertise variable Nuclear Cardiology Regional blood flow Attenuation issues Source: Charney 2002, Greenland 2007

29 Drawbacks of Diagnostic Imaging in Women Low exercise capacity –  likelihood of reaching adequate pressure rate product –Solution: Pharmacologic stress testing Breast attenuation artifact – higher false positive imaging studies –Solution: Gated acquisition; attenuation correction for nuclear imaging –Solution: Echocardiography Lower pretest probability of CAD – higher false positive rate –Solution: Integrate clinical variables, risk factors, into decision-making process Source: Duvernoy, personal communication

30 Women and CHD: What Test to Order When For women at high or intermediate risk of coronary artery disease, consider treadmill echocardiogarphy or nuclear perfusion imaging For women unable to exercise, consider dobutamine stress echocardiography or adenosine or dipyridamole nuclear imaging In high risk women with typical symptoms of coronary artery disease, consider referral to a cardiologist For high risk women, consider cardiac catheterization if symptoms persist despite negative non-invasive imaging Source: Anderson 2007, Klocke 2003, Douglas 2008, Duvernoy 2005

31 Women and CHD: What Test to Order When A stepwise approach beginning with conventional exercise testing may be considered for women who: –Are at low or intermediate risk for coronary artery disease –Are able to exercise –Have an electrocardiogram that can be interpreted during stress testing An image-enhanced test may be more predictive in women than conventional electrocardiogram stress testing, and may also be more cost effective in women at intermediate risk for CHD Source: Anderson 2007, Klocke 2003, Douglas 2008,Mieres 2005

32 Mosca L et al. Circulation. 2004;109: and Circulation 2007; 115:

33 Say ALOHA to Heart Disease in Women A – Assess your risk: high, intermediate, or low?A – Assess your risk: high, intermediate, or low? L – Lifestyle recommendations are first priorityL – Lifestyle recommendations are first priority O – Other interventions prioritized according to expert panel rating scaleO – Other interventions prioritized according to expert panel rating scale H – Highest priority for therapy is for women at highest riskH – Highest priority for therapy is for women at highest risk A – Avoid medical therapies called Class III where evidence is lackingA – Avoid medical therapies called Class III where evidence is lacking Mosca L. Circulation 2004

34 A - Assessment of CHD Risk For persons without known CHD, other forms of atherosclerotic disease, or diabetes: Count the number of risk factors. Use Framingham scoring if  2 risk factors* to determine the absolute 10-year CHD risk. Determine risk status: high (>20% 10-year risk or CHD risk equivalents), intermediate (10-20% 10- year risk), or low (<10% risk) *For persons with 0–1 risk factor, Framingham calculations are not necessary. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285: © 2001, Professional Postgraduate Services ®

35 Point Total10-Year RiskPoint Total10-Year Risk <9<1%2011% 91%2114% 101%2217% 111%2322% 121%2427% 132%  25  30% 142% 153% 164% 175% 186% 198% Assessing CHD Risk in Women Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285: Step 1: Age YearsPoints TC Points atPoints atPoints atPoints atPoints at (mg/dL) Age 20-39Age 40-49Age 50-59Age 60-69Age <  HDL-C (mg/dL) Points  <402 Step 3: HDL-Cholesterol Systolic BPPointsPoints (mm Hg)if Untreatedif Treated <  Step 4: Systolic Blood Pressure Step 5: Smoking Status Nonsmoker00000 Smoker97421 Age Total cholesterol HDL-cholesterol Systolic blood pressure Smoking status Point total Step 6: Adding Up the Points Step 7: CHD Risk Step 2: Total Cholesterol ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ®

36 A - Assessment of CHD Risk Classification of CVD Risk in Women (Mosca et al., Circ 2007) High Risk:High Risk: –Established coronary heart disease –Cerebrovascular disease –Peripheral arterial disease –Abdominal aortic aneurysm –End-stage or chronic renal disease –Diabetes mellitus –10-year Framingham global risk >20%

37 Classification of CVD Risk in Women (Mosca et al., Circ 2007) At Risk:At Risk: –Evidence of subclinical vascular disease (e.g., coronary calcium) –Metabolic Syndrome –Poor exercise capacity on treadmill and/or abnormal heart rate recovery –>=1 major risk factor for CVD including: Cigarette smokingCigarette smoking Poor dietPoor diet Physical inactivityPhysical inactivity Obesity (esp central obesity)Obesity (esp central obesity) Family history of premature CVD (<55 male or <65 female relative)Family history of premature CVD (<55 male or <65 female relative) HypertensionHypertension DyslipidemiaDyslipidemia Optimal risk: Framingham global risk <10% and a healthy lifestyle with no risk factorsOptimal risk: Framingham global risk <10% and a healthy lifestyle with no risk factors

38 Priorities for Prevention in Practice According to Risk Assessment High-Risk Women (>20% Risk) Intermediate-Risk Women (10% to 20% Risk) Lower-Risk Women (10% Risk) Class I recommendations Smoking cessation Phys activity/card rehab Diet therapy Weight maint/reduct BP control Cholest control/Rx Aspirin therapy -Blocker therapy ACE inhibitor (ARBs) Mgmt/control of DM Smoking cessation Physical activity Heart-healthy diet Weight maint/reduct BP control Cholesterol control Smoking cessation Physical activity Heart-healthy diet Weight maint/reduct Treat individual heart risk factors as indicated Class IIa recommendation Treatment for depression Aspirin therapy Class IIb recommendations Omega 3 fatty-acid supplementation Folic acid supplementation Mosca, L “Heart Disease Prevention in Women” Circulation, 2004

39 L – Lifestyle Change: First Line of Defense Against Heart Disease The AHA expert panel rated the following as Class I recommendations:The AHA expert panel rated the following as Class I recommendations: –Stop cigarette smoking and avoid secondhand tobacco smoke –Get at least 30 minutes of physical activity most or preferably all days (60-90 minutes for those needing to lose or sustain weight) –Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event –Eat a heart-healthy diet (consistent with NCEP/ATP III TLC) –Maintain healthy weight by balancing caloric intake with caloric expenditure to achieve BMI between kg/m 2 Mosca et al. Circulation 2004 and 2007

40 Essential Components of NCEP Therapeutic Lifestyle Change (TLC) Decrease in saturated fats (<7% of total calories) and trans fatty acids 1 Increased dietary and supplemental fiber 1 –High-fiber breakfast cereals, supplements, and so forth Plant sterols and stanols (2 g/d) 1 –Spreads, pills, added to yogurt or other foods, or combined with aspirin Soy protein 2 Flavonoids (nuts) 3 Weight loss 1 Exercise 1 1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285(19): Sacks FM, et al; American Heart Association Nutrition Committee. Circulation. 2006;113(7): Kelly JH Jr and Sabaté J. Br J Nutr. 2006;96(suppl 2):S61-S67.

41 Aspirin in Primary Prevention: Effective Gender Differences Ridker, P. et al., N Engl J Med 2005; 352: BDT, 1988 Combined PPP, 2001 HOT, 1998 TPT, 1998 PHS, 1989 RR of MI Among Men 2.0 RR = 0.68 (0.54–0.86) P =.001 RR of Stroke Among Men RR = 1.13 (0.96–1.33) P = HOT, 1998 Combined WHS, 2005 PPP, 2001 RR of MI Among Women Aspirin Better Placebo Better RR = 0.99 (0.83–1.19) P = Aspirin Better Placebo Better 1.0 RR of Stroke Among Women RR = 0.81 (0.69–0.96) P =

42 Blood Pressure Regulation in Women 3 of every 4 women with high blood pressure know they have it3 of every 4 women with high blood pressure know they have it Fewer than 1 in 3 are controlling itFewer than 1 in 3 are controlling it All women must take steps to control their high blood pressureAll women must take steps to control their high blood pressure NIH Web site. Your guide to lowering high blood pressure: issues for women. Available at:

43 AHA Guidelines for CVD Prevention in Women: Blood Pressure Encourage an optimal blood pressure of <120/80 mm Hg through lifestyle approaches (Class I, Level B)Encourage an optimal blood pressure of <120/80 mm Hg through lifestyle approaches (Class I, Level B) Pharmacotherapy when BP isPharmacotherapy when BP is –  140/90 mm Hg Get BP even lower whenGet BP even lower when –Target-organ damage –Diabetes (Class I, Level A) Mosca L et al. J Am Coll Cardiol. 2004;43:

44 CHD Risk Equivalents > 20% 10-year risk of CHD (Framingham projections) (downloadable risk algorithms at Diabetes Other forms of clinical atherosclerotic disease –Peripheral arterial disease (ABI <0.90) –Abdominal aortic aneurysm –Carotid artery disease (>=1mm CIMT?) NCEP ATP III. JAMA. 2001;285:

45 Other Modalities for Measuring Atherosclerotic Burden Carotid B-mode ultrasonography: intimal medial thicknesses Ankle-Brachial Index (ABI) for assessment of peripheral vascular disease CT (EBT or multislice detectors): coronary calcium score or volume Magnetic resonance imaging of carotid plaques: vessel wall area Intravascular ultrasound (invasive)

46 Recommendations for Noninvasive Screening AHA Prevention V (Greenland et al., Circ. 2000) indicated persons at intermediate risk may be suitable for screening by noninvasive tests, including ABI and carotid US for those over age 50 years, and coronary calcium screening. ATP III has suggested CAC scores above 75 th percentile indications for more aggressive treatment (e.g., as CHD risk equivalent).

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48 Cardiovascular Health Study: Combined intimal-medial thickness predicts total MI and stroke Cardiovascular Health Study (CHS) (aged 65+): MI or stroke rate 25% over 7 years in those at highest quintile of combined IMT (O’Leary et al. 1999)

49 Significant Coronary Artery Calcium (Score >400)

50 Risk of Total Mortality by Calcium Category in 10,377 Asymptomatic Individuals Shaw LJ et al., Radiology 2003; 228:

51 L – Lifestyle Change: First Line of Defense Against Heart Disease The AHA expert panel rated the following as Class I recommendations: –Stop cigarette smoking and avoid secondhand tobacco smoke –Get at least 30 minutes of physical activity each day –Start a cardiac rehabilitation program if recently hospitalized for heart disease –Eat a heart-healthy diet –Maintain healthy weight by balancing caloric intake with caloric expenditure Mosca et al. Circulation 2004

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53 ATP III: Nutritional Components of the TLC Diet Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285: *Trans fatty acids also raise LDL-C and should be kept at a low intake. Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight. <200 mg/dCholesterol ~15% of total caloriesProtein 20–30 g/dFiber 50%–60% of total caloriesCarbohydrate (esp. complex carbs) 25%–35% of total calories Total fat Up to 20% of total calories Monounsaturated fat Up to 10% of total calories Polyunsaturated fat <7% of total caloriesSaturated fat* Recommended IntakeNutrient © 2001, Professional Postgraduate Services ®

54 Possible Benefits From Other Therapies Therapy Result Soluble fiber in diet (2–8 g/d) (oat bran, fruit, and vegetables) Soy protein (20–30 g/d) Stanol esters (1.5–4 g/d) (inhibit cholesterol absorption) Fish oils (3–9 g/d) (n-3 fatty acids)  LDL-C 1% to 10%  LDL-C 5% to 7%  LDL-C 10% to 15%  Triglycerides 25% to 35% Jones PJ. Curr Atheroscler Rep. 1999;1: Lichtenstein AH. Curr Atheroscler Rep. 1999;1: Rambjor GS et al. Lipids. 1996;31:S45-S49. Ripsin CM et al. JAMA. 1992;267:

55 Nuts, Soy, Phytosterols, Garlic Nurses’ Health Study: five 1oz servings of nuts per week associated with 40% lower risk of CHD events; 2-4 servings/wk 25% lower risk Metaanalysis of 38 trials of soy protein showed 47g intake lowered total, LDL-C, and trigs 9%, 13%, and 11%, respectively; no effect on HDL-C. Phytosterol-supplemented foods (e.g., stanol ester margarine) lowers LDL-C avg. 10% Meta-analysis of garlic studies showed 9% total cholesterol reduction from 1/2-1 clove consumed daily for 6 months.

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57 Health Benefits of Weight Loss Decreased cardiovascular risk Decreased glucose and insulin levels Decreased blood pressure Decreased LDL and triglycerides, increased HDL Decrease in severity of sleep apnea Reduced symptoms of degenerative joint disease Improved gynecological conditions

58 National Obesity Education Initiative Treatment Algorithm Patient Encounter Hx of 25 BMI?  Measure weight, height, and waist circumference Calculate BMI Examination Brief reinforcement/ educate on weight management Periodic weight check Advise to maintain weight/address other risk factors Clinician and patient devise goals and treatment strategy for weight loss and risk factor control Assess reasons for failure to lose weight Maintenance counseling: Dietary therapy Behavior therapy Physical activity : Treatment Assess risk factors No Yes Yes No Yes No Hx BMI 25?  No Yes No Does patient want to lose weight? Yes No Progress being made/goal achieved? BMI 25 OR  waist circumference > 88 cm (F) > 102 cm (M) BMI  30 OR {[BMI 25 to 29.9 OR waist circumference >88 cm (F) >102 cm (M)] AND 2 risk  factors} BMI measured in past 2 years?

59 Whenever possible, weight loss therapy should employ the combination of Low-calorie/low-fat diets Increased physical activity Behavior modification Weight Loss Therapy

60 O – Other Interventions with Class I Recommendations Blood pressure – encourage optimal levels of <120/80 mmHg Cholesterol levels – optimal cholesterol levels 50 mg/dl, triglycerides <150 mg/dl Diabetes – recommend control to HgbA1c < 7%

61 Evidence-based Guidelines for CVD Prevention in Women – Major Risk Factor Interventions (Mosca et al., Arterioscler Throm Vasc Biol 2004; 24: e29-e50)

62 I have some bad news for you. While your cholesterol has remained the same, the research findings have changed.

63 When LDL-lowering drug therapy is employed in high-risk or moderately high risk patients, intensity of therapy should be sufficient to achieve a 30–40% reduction in LDL-C levels.

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65 JNC-7 New Features and Key Messages  Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes.  Certain high-risk conditions are compelling indications for other drug classes.  Most patients will require two or more antihypertensive drugs to achieve goal BP.  If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.

66 H – Highest Priority for Therapy is for Women at Highest Risk Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the following Class I recommendations: –ACE inhibitor therapy (if coughing, subst. ARB) –Aspirin therapy (baby aspirin or maximum dose of 162 mg) unless contraindicated –Beta-blocker therapy in those with prior MI or current angina –Statin therapy –Niacin or fibrate therapy if low HDL present –Fibrates to lower triglycerides and improve HDL –Warfarin in those with atrial fibrillation unless contradindicated

67 H – Highest Priority for Therapy is for Women at Highest Risk Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the following Class I recommendations:Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the following Class I recommendations: –ACE inhibitor therapy (if coughing, subst. ARB) –Aspirin therapy (baby aspirin or maximum dose of 162 mg) unless contraindicated –Beta-blocker therapy in those with prior MI or current angina –Statin therapy –Niacin or fibrate therapy if low HDL present –Fibrates to lower triglycerides and improve HDL –Warfarin in those with atrial fibrillation unless contradindicated

68 A – Avoid “Class III” Interventions (Not proven useful or effective / may be harmful) Combined estrogen and progestin therapy, and *estrogen monotherapy since associated with increased risk of CVDCombined estrogen and progestin therapy, and *estrogen monotherapy since associated with increased risk of CVD Selective estrogen-receptor modulators (SERMs) also not recommendedSelective estrogen-receptor modulators (SERMs) also not recommended Antioxidant supplements including vigtamin E, C, and beta- caroteneAntioxidant supplements including vigtamin E, C, and beta- carotene Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged <65 yearsAspirin for MI prevention in women aged <65 years

69 Vitamins: Major Vascular Events Vascular Event Major coronary Any stroke Revascularization Any of the above2306 (22.5%) 2312 (22.5%) Heart Protection Study Collaborative Group. Lancet. 2002;360:23–33. Risk Ratio and 95% CI Vitamin Better Vitamin Worse (0.94–1.06) P > 0.9 Vitamins (n = 10,269) Placebo (n = 10,267)

70 Does Hormone Replacement Therapy Prevent Heart Disease? Epidemiologic studies over the past several decades together have shown approximately a 50% lower risk in women randomized to estrogen replacement therapy vs. placebo Even the Nurses’ Health Study showed those on estrogen/progestin to have approximately a 60% lower risk of heart disease events

71 Heart and Estrogen/Progestin Replacement Study (HERS): Secondary Prevention of CHD in Women Randomized, placebo-controlled trial of E/P therapy vs. placebo in 2763 women with CHD; average age 67 years Treatment was mg CEE mg medroxyprogesterone daily for 4 years Primary endpoint: nonfatal MI and CHD death Secondary endpoints: CABG, PTCA, unstable angina, CHF, PVD, TIA JAMA 1998;280:

72 HERS Results No statistically significant difference between HRT and placebo in both primary and secondary endpoints after 4 years. Within first year, greater incidence in CHD events in HRT group. In years 3 and 4, lower CHD events in HRT group compared to placebo. HRT lowered LDL 11% and increased HDL 10% compared to placebo. Approximately 50% of randomized women were on lipid- lowering drugs. Higher incidence of VTE and cholelithiasis in HRT group.

73 More Bad News: The Women’s Health Initiative Over 160,000 women nationwide, aged and postmenopausal have participated in various components (observational, dietary modification, and HRT clinical trials)—over 3,000 at UCI The Estrogen/Progestin component of the HRT clinical trial involving 16,608 women nationwide was discontinued prematurely in Spring 2002 after 5.2 years of follow-up (instead of 8.5 years).

74 WHI Estrogen/Progestin and Estrogen Only Results Those randomized to estrogen/progestin compared to placebo and statistically significant increased risks: –Breast cancer 26% (8/10,000 person years) –Total coronary heart disease 29% (7/10,000 person years) –Stroke 41% (8/10,000 person years) –Pulmonary emobolism 2.1 X (8/10,000 person years) –Protective for colorectal cancer (37% lower) and hip fracture (34% lower): no effect endometrial cancer or total mortality JAMA Jul 17;288(3): Estrogen-only arm was also recently discontinued in December 2003 and was associated with a 39% increased risk of stroke (12 excess strokes per 10,000 person years) and 12% significant increased risk of cardiovascular events. JAMA Apr 14;291(14):

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76 Women Making a Change

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78 For More Information about Preventing Heart Disease: Preventive Cardiology, 2 nd ed. from McGraw-Hill ….. For more information, see the UCI Heart Disease Prevention Website at


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