Presentation on theme: "Robert M. Guthrie, MD Professor of Emergency Medicine"— Presentation transcript:
1 Dyslipidemia and Cardiovascular Risk Reduction: An Evidence-Based Review Robert M. Guthrie, MDProfessor of Emergency MedicineProfessor of Internal MedicineProfessor of PharmacologyThe Ohio State University College of MedicineColumbus, Ohio
2 ? Key Question What percentage of your patients with dyslipidemia who are receiving statintherapy alone achieve LDL goal?<25%26%-50%51%-75%76%-100%Use your keypad to vote now!The correct answer is 3.
4 Learning ObjectivesDiscuss current guidelines for the management of dyslipidemiaDescribe the results of recent clinical trials relevant to the management of dyslipidemiaState lipid goals according to patients’ level of cardiovascular risk
5 Cardiovascular Disease (CVD) Leading cause of death in the United States37% of all US deaths in 20031Total US cost in 2006 = $403.1 billion1Associated with high blood levels of cholesterol and other lipids, and low HDL levels1Risk assessment, risk reduction1,2Cardiovascular disease (CVD) is the leading cause of death in the United States, accounting for 37% of all deaths inIn addition, CVD is costly in terms of morbidity and lost productivity. The total cost of CVD (including stroke) in the United States in 2006 was estimated at $403.1 billion.1This includes direct costs of $257.6 billion (for medical care) and indirect costs of $145.5 billion (from lost productivity due to morbidity and mortality).1One of the major risk factors for development of CVD is high levels of blood cholesterol and other lipids, along with low levels of high-density lipoprotein cholesterol (HDL).1Prevention of CVD requires assessment of risk, followed by risk-reduction therapy—especially efforts to reduce increased levels of low-density lipoprotein cholesterol (LDL).1,2References:Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006;113:e85-e151.Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:HDL: high-density lipoprotein1. Thom T, et al. Circulation. 2006;113:e85-e151.2. NCEP ATP III. JAMA. 2001;285:
6 NCEP ATP III Risk Determinants LDL levelCHD or CHD risk equivalents:Other clinical atherosclerotic diseaseDiabetesMultiple other risk factors contributing to a Framingham 10-year risk of CHD >20%Other major risk factorsRisk assessment begins with these major risk determinants.High levels of LDL are considered a major cause of coronary heart disease (CHD), and reduction of LDL is the primary target of therapy.The presence of CHD or CHD risk equivalents puts a patient in the highest risk category. Risk equivalents for CHD include the following:Other clinical forms of atherosclerotic disease (peripheral arterial disease, peripheral vascular disease, abdominal aortic aneurysm, symptomatic carotid artery disease, or stroke)DiabetesMultiple other risk factors creating a Framingham 10-year risk of CHD greater than 20%Other major risk factors for development of CVD and CHD are shown on the next slide.Reference:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:NCEP ATP III: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)LDL: low-density lipoproteinCHD: coronary heart diseaseNCEP ATP III. JAMA. 2001;285:
7 Major Risk Factors Other Than LDL and CHD Cigarette smokingHypertensionBP ≥140/90 mm Hg or on antihypertensive medicationLow HDL level<40 mg/dLFamily history of premature CHDMale first-degree relative <55 yearsFemale first-degree relative <65 yearsAgeMen ≥45 yearsWomen ≥55 yearsAlthough the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) emphasize an increase in LDL as the chief risk factor for CHD, they also recognize several other major risk factors that should be considered when setting LDL treatment goals:Cigarette smokingHypertensionLow HDL levelFamily history of premature CHDOlder ageReference:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:BP: blood pressureNCEP ATP III. JAMA. 2001;285:
8 NCEP ATP III Risk Definitions TestOptimalBorderline High RiskHigh RiskVery High RiskTotal Cholesterol<200≥240LDL<100≥190HDL≥6040-59<40Triglycerides<150≥500Here is a summary table of the NCEP ATP III risk definitions for each lipid parameter that you may find helpful.Levels of LDL between 100 and 129 mg/dL are considered “near or above optimal.”Levels of HDL less than 40 mg/dL are considered low and are associated with an increased risk of CHD.A level of HDL of ≥60 mg/dL is considered high.Reference:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:NCEP ATP III. JAMA. 2001;285:
9 Risk Assessment: Dyslipidemia and CVD Framingham risk calculator1,2Based on age, sex, total and HDL cholesterol, smoking, BPMobile Lipid Clinic3Free NCEP ATP III–based toolsPalm® and Windows®Reynolds risk calculator4For healthy women without diabetes1. Risk assessment tool for estimating 10-year risk of developing hard CHD (myocardial infarction and coronary death). Available at Accessed on January 17, 2007.2. Grundy SM, et al. J Am Coll Cardiol. 1999;34:3. Mobile Lipid Clinic. Available at Accessed on January 17, 2007.4. Reynolds Risk Score. Available at Accessed on February 23, 2007.Risk assessment requires a physical exam, medical history, and values from a fasting lipid panel.Two user-friendly tools can help you manage patients with dyslipidemia:The Framingham risk calculator can be accessed online and provides a rapid estimation of 10-year risk of CVD.1 Please note that any formula is only an estimation of population-based risk and that as the population changes, the risk levels may also change. The Framingham data were collected several years ago. In addition, population-level data are means; an individual patient’s results can vary.2 The online calculators are easy to use and provide a continuous correlation to risk. The Framingham point system, on the other hand, calculates categoric risk. The 2 results may not coincide for a given patient.The Mobile Lipid Clinic offers a free set of downloadable tools to help clinicians educate, track, and manage patients with dyslipidemia.3The Reynolds Risk Score is based on a 6-item questionnaire and is designed to calculate the 10-year risk of future heart attack, stroke, or other major heart disease.References:Risk assessment tool for estimating 10-year risk of developing hard CHD (myocardial infarction and coronary death). Available at Accessed on January 17, 2007.Grundy SM, Pasternak R, Greenland P, et al. Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol. 1999;34:3. Mobile Lipid Clinic. Available at Accessed on January 17, 2007.4. Reynolds Risk Score. Available at Accessed on February 23, 2007.
10 NCEP ATP III Risk Categories Risk CategoryCriteriaLow risk0-1 risk factorModerate risk≥2 risk factors;10-year risk <10%Moderately high risk10-year risk 10%-20%High riskCHD or CHD risk equivalents;10-year risk >20%According to the NCEP ATP III criteria, patients with fewer than 2 risk factors are at low risk.Patients at moderate risk of a cardiovascular event would have at least 2 risk factors and a Framingham 10-year risk of less than 10%. If the Framingham risk is between 10% and 20%, these individuals would be placed in the moderately high-risk category.Patients at high risk of cardiovascular events would have pre-existing CHD or a CHD equivalent such, as diabetes, and/or a 10-year Framingham risk that exceeds 20%.Reference:Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:Grundy SM, et al. Circulation. 2004;110:
11 DyslipidemiaPresence of abnormal levels of blood lipids and lipoproteins1Diagnosed using fasting lipoprotein profile1Nearly 40% of US adults have LDL levels ≥130 mg/dL (borderline high or higher)2An important part of risk assessment is testing for dyslipidemia—the presence of abnormal levels of blood lipids and lipoproteins—by obtaining a fasting lipoprotein profile.1A large number of US adults have dyslipidemia. In 2003, nearly 40% of the US population had an LDL level of 130 mg/dL or higher, which means that their LDL levels were borderline high or higher.2References:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006;113:e85-e151.1. NCEP ATP III. JAMA. 2001;285:2. Thom T, et al. Circulation. 2006;113:e85-e151.
12 ? Key Question Why do so many patients have high lipid levels? Lack of screening and treatment by cliniciansLack of effective medicationsLack of therapy adherence by patients1 and 3All of the aboveUse your keypad to vote now!The correct answer is 4.
13 Problem: Low Success Rates in Achieving Lipid Goals % Patient SuccessPROBLEM: Failure to reach lipid goals remains a problem, despite the use of lipid-lowering agents.1In one survey, only 38% of patients with dyslipidemia reached lipid targets; success rates were highest in low-risk patients (68%), moderate in high-risk patients (37%), and lowest in patients with CHD (18%).1This failure is attributable to both physician-related factors and patient-related factors.Physician- or clinician-related factors include the following:Physicians’ compliance with lipid guidelines for screening and intervention is suboptimal.2,3Patients at risk are not being screened or started on treatment adequately.3SOLUTION: Clinicians should increase their efforts to follow current guidelines regarding screening of at-risk populations and increase efforts to implement current guidelines for effective treatment. These guidelines will be discussed beginning on slide 12.Patient-related factors include the following:Long-term adherence to lifestyle modifications and medication regimens is less than optimal.3SOLUTION: Efforts to help patients improve long-term adherence are discussed in slides 38 to 40.References:Pearson TA, Laurora I, Chu H, et al. The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160:Frolkis JP, Zyzanski SJ, Schwartz JM, et al. Physician noncompliance with the 1993 National Cholesterol Education Program (NCEP-ATPII) guidelines. Circulation. 1998;98:Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Final Report. National Cholesterol Education Program. National Institutes of Health. National Heart, Lung, and Blood Institute. NIH publication no September 2002.Risk GroupsPearson TA, et al. Arch Intern Med. 2000;160:
14 Problem: Patients’ Adherence to Statin Therapy Overall Persistence (%)A recent study of patients’ adherence to statin medications based on analysis of pharmacy records found that overall persistence (the percentage of patients who continued to take their medications over that time period) decreased from 56% at 9 months to 35% at 12 months.This decrease in adherence was seen across subgroups of patients: men, women, younger, older, and those who did or did not pay directly for their medications.At the end of the study, adherence was 34% for men, 18% for women, 19% for patients less than 65 years old, and 41% for patients aged 65 years and older.Statin adherence at 12 months was greatest among men aged 65 years and older and lowest among women younger than 65 years of age. This discrepancy may reflect differing perceptions of risk. That is, older men are more likely to appreciate their risk of heart disease and therefore are more likely to adhere to medications to reduce that risk.Another measure of medication adherence is the number of gap days between prescription refills, an indication that patients are taking their medications inconsistently. The number of gap days between prescription refills was longer for women than for men, indicating lower adherence among women.Thus, an urgent need exists for primary care clinicians to counsel their patients more effectively regarding their risk of CVD and the benefits of therapeutic lifestyle changes and medical regimens to reduce this risk. Clinicians can use several strategies to help patients increase their overall adherence to therapeutic measures; these will be discussed in slides 38 to 40.Reference:Huser MA, Evans TS, Berger V. Medication adherence trends with statins. Adv Ther. 2005;22:Huser MA, et al. Adv Ther. 2005;22:
15 NCEP Guidelines in a Nutshell Identify individuals at high risk of CV events:10-year risk >20%10-year risk 10%-20%Start therapeutic lifestyle changes and/or medicationAdjust intensity of therapy to individual risk levelMonitor progress to goal lipid controlIn a nutshell: To obtain the greatest possible benefit, we want to do the following:Identify individuals at increased risk of CHD and cardiovascular (CV) events.Start appropriate treatment.Monitor that treatment to ensure that it allows our patients to achieve goals for lipid control.One of our challenges as clinicians is to target our activity to achieve the greatest impact despite limited time and other resources. The benefit of dyslipidemia treatment is greatest in patients who are at high risk (>20% risk in 10 years). Therefore, key elements of dyslipidemia management are to identify those high-risk patients, treat them to goal, and track their progress.At a 10% risk level or higher, the risk is considerable. Patients may start with lifestyle changes, but most will need to add lipid-lowering medications.When we see patients who are currently at lower levels of risk, we can use this opportunity to inform them about their possible future health condition and what they can do to avoid poor cardiovascular outcomes. This information can help motivate them to follow through.Reference:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:Adherence is always a factorCV: cardiovascularNCEP ATP III. JAMA. 2001;285:
16 NCEP ATP III 2001 Thresholds for LDL-Lowering Therapy TLC(mg/dL)Consider DrugTherapy (mg/dL)Low Risk0-1 risk factor≥160≥190(optional at )Moderate Risk2 risk factors;10-year risk <10%≥130Moderately High Risk10-year risk 10%-20%(optional at )High RiskCHD or CHD risk equivalents;10-year risk >20%≥100(optional at <100)The NCEP ATP III 2001 threshold levels for LDL treatment depend on the extent of underlying risk.For low-risk patients, therapeutic lifestyle change (TLC) is advocated when LDL exceeds 160 mg/dL, and drug therapy is recommended when LDL reaches 190 mg/dL or higher.1 Recommendations from 2004 suggest that an LDL-lowering drug is optional at LDL levels between 160 mg/dL and 189 mg/dL.2For moderate-risk patients, lifestyle change is recommended when LDL exceeds 130 mg/dL, and drug therapy is needed when LDL levels reach or exceed 160 mg/dL.1For moderately high-risk patients, lifestyle change is recommended when LDL exceeds 130 mg/dL, and drug therapy is needed when LDL levels reach or exceed 130 mg/dL.1 Recommendations from 2004 suggest that an LDL-lowering drug is optional at LDL levels between 100 mg/dL and 129 mg/dL.2For high-risk patients, lifestyle change is advocated when LDL levels exceed 100 mg/dL, and drug therapy is needed when levels reach or exceed 130 mg/dL.1 Recommendations from 2004 advise drug therapy when levels reach or exceed 100 mg/dL and suggest that an LDL-lowering drug is optional at LDL levels less than 100 mg/dL.2References:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:TLC: therapeutic lifestyle changes1. NCEP ATP III. JAMA. 2001;285:2. Grundy SM, et al. Circulation. 2004;110:
17 NCEP ATP III Thresholds: Update 2004 Very high-risk patientsLDL ≥100 mg/dL consider drug therapyLDL goal <70 mg/dL a therapeutic optionModerately high-risk patientsLDL goal <100 mg/dL a therapeutic optionHigh-risk and moderately high-risk patients30%-40% reduction in LDL recommendedHigh-risk patients with high TG or low HDL levelsConsider fibrate or nicotinic acidHigh-risk or moderately high-risk patients with lifestyle-related risk factorsTherapeutic lifestyle change regardless of LDLRecent clinical trials with statin therapy provide a sound basis for lower target LDL levels with the use of more intensive LDL-lowering therapy.On the basis of findings from recent key studies, an expert panel developed the NCEP Interim Report and recommended the following key changes to the 2001 NCEP ATP III guidelines:In high-risk patients, consider drug therapy when LDL reaches 100 mg/dL, with an LDL goal of less than 70 mg/dL as a therapeutic option, especially for those patients considered to be at very high risk.For patients at moderately high risk, an LDL goal of less than 100 mg/dL is a therapeutic option.For high-risk or moderately high-risk patients, the intensity of LDL-lowering therapy should be sufficient to achieve at least a 30% to 40% reduction in LDL levels.The addition of a fibrate or nicotinic acid as part of LDL-lowering therapy should be considered in high-risk patients with high triglyceride (TG) levels or low HDL levels.Further, any high-risk or moderately high-risk individual with lifestyle-related risk factors is a candidate for therapeutic lifestyle change, regardless of LDL level.Reference:Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:TG: triglycerideGrundy SM, et al. Circulation. 2004;110:
18 NCEP ATP III Therapeutic Goals for LDL Risk CategoryLDL Goal (mg/dL)Low risk0 to 1 risk factor<160Moderate risk2 risk factors; 10-year risk <10%<130Moderately high risk2 risk factors; 10-year risk 10%-20%(optional goal <100)High riskCHD or CHD risk equivalents; 10-year risk >20%<100(optional goal <70 for very high-risk patients)Risk categories are assigned based on Framingham 10-year risk scores and presence of major risk factors.1Specific LDL goals are associated with the various risk categories.Therapeutic lifestyle changes are indicated when a patient’s LDL level is above the goal.1Therapy with an LDL-lowering drug should be considered when LDL levels exceed goal in moderately high-risk and high-risk patients, when LDL levels are 160 mg/dL or higher in moderate-risk patients, and when LDL levels are 190 mg/dL or higher in low-risk patients.1Beyond the use of Framingham risk scoring, clinical judgment is essential in deciding when to use lipid-lowering agents.The first line of therapy for lowering LDL levels is one of the statins.1For patients at high risk who also have high triglycerides or low HDL, consider combination therapy with a fibrate or nicotinic acid in addition to an LDL-lowering drug.1The LDL goals set by the NCEP ATP III 2001 guidelines advocate a reduction to less than 160 mg/dL in low-risk patients, to less than 130 mg/dL in moderate-risk patients, and to less than 100 mg/dL in high-risk patients.1A 2004 review of data published after the NCEP ATP III guidelines of 2001 suggested modifications of the LDL level for moderately high-risk, high-risk, and very high-risk patients, as shown in orange on this table.2When LDL-lowering drug therapy is used in moderately high-risk or high-risk patients, the goal should be to achieve at least a 30% to 40% reduction in LDL levels.2References:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:1. NCEP ATP III. JAMA. 2001;285:2. Grundy SM, et al. Circulation. 2004;110:
19 Review of Key Clinical Trials Conducted in 2005 Risk CategoryLDL Goal (mg/dL)High riskCHD or CHD risk equivalents;10-year risk >20%<77Persons with diabetes and CHD should be treated aggressively with statins, even if they are not otherwise at high riskThe first line of therapy should continue to be statins rather than fibrates (which are still useful in combination therapy)A review by Cheng and Leiter published in 2006 discussed the results from key clinical trials of 2005.The authors concluded the following:The recent trials support an approximate LDL target of less than 77 mg/dL for all high-risk patients, rather than an LDL goal of less than 70 mg/dL only for very high-risk patients.This target requires higher-dose statin therapy. The substantial clinical benefits (decreased risk of major coronary events and/or coronary mortality) are believed to outweigh a slight increase in adverse events (most of which are not serious) with higher-dose statins.Individuals with diabetes and CHD, even those who are considered not to be at high risk, should be treated aggressively with statins.The first line of therapy should continue to be statins rather than fibrates (which are still useful in combination therapy).Reference:Cheng AYY, Leiter LA. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Curr Opin Cardiol. 2006;21:Cheng AY, Leiter LA. Curr Opin Cardiol. 2006;21:
20 Importance of Individualized Dyslipidemia Management Dyslipidemia is a complex disease caused by the interplay of genetic, dietary, and physiologic factorsDyslipidemia often occurs concurrently with other medical conditionsTreatment strategy is evolving based on new dataDyslipidemia represents a complex disease that often results from the intersection of genetic, dietary, and physiologic factors.Dyslipidemia often does not occur in isolation; rather, it emerges as part of a cluster of metabolic disturbances that increase the risk of CVD.In recent years, clinical trial data have spurred important revisions in the guidelines for the management of dyslipidemia, including a reexamination of LDL goals.
21 Metabolic Syndrome Definitions: NCEP ATP III and IDF ComponentsNCEP ATP III1≥3 ComponentsIDF2WC + ≥2 ComponentsWaist Circumference (WC; inches)≥40 (men); ≥34.5 (women)Europid≥37 (men); ≥31.5 (women)South Asians≥35.50 (men); ≥31.5 (women)JapaneseTriglycerides (mg/dL)≥150HDL (mg/dL)<40 (men); <50 (women)BP (mm Hg)Systolic ≥130 or diastolic ≥85Fasting Plasma Glucose (mg/dL)≥100Several organizations have proposed definitions of metabolic syndrome. Metabolic syndrome comprises a cluster of abnormalities—including dyslipidemia—that heightens the risk of CVD and diabetes.This slide shows the criteria for metabolic syndrome according to the NCEP ATP III1 and the International Diabetes Federation (IDF).2The NCEP and IDF both focus on abdominal obesity, dyslipidemia, high blood pressure, and increased glucose levels as central features; abdominal obesity is a necessary component in the IDF definition.References:Grundy SM, Cleeman JI, Daniels SR, et al; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:International Diabetes Federation. Rationale for new IDF worldwide definition of metabolic syndrome. Available at Accessed on February 3, 2007.IDF: International Diabetes Federation1. Grundy SM, et al. Circulation. 2005;112:2. International Diabetes Federation. Rationale for new IDF worldwide definition of metabolic syndrome. Available at Accessed on February 3, 2007.
22 Prevalence of Metabolic Syndrome: NHANES III 1988-1994 Percent AffectedData from 8814 men and women at least 20 years old who participated in the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994 were assessed to estimate the prevalence of metabolic syndrome (as defined by the NCEP ATP III).Prevalence increased from 6.7% at ages 20 to 29 years to more than 40% in those aged 60 years and older. Thus, metabolic syndrome is more common in older age groups.The overall prevalence differed little between men and women across age groups.Reference:Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:20-2930-3940-4950-5960-6970+Age (years)NHANES III: Third National Health and Nutrition Examination SurveyFord ES, et al. JAMA. 2002;287:
23 Metabolic Syndrome Prevalence by Race and Ethnicity % AffectedAcross the ethnic groups examined, the prevalence of metabolic syndrome was highest among Mexican Americans, at 31.9%.Among African Americans, the prevalence was 57% higher among women than men, and among Mexican Americans, women had a 26% higher prevalence than men.Applying these rates to the 2000 Census population indicates that 47 million US residents have metabolic syndrome.Reference:Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:Ford ES, et al. JAMA. 2002;287:
24 Pattern of Dyslipidemia in Type 2 Diabetes Triglycerides HDLQualitative changes in LDLHigher proportion of smaller and denser LDL particles susceptible to oxidation and atherogenicityMean LDL levels not different in high-risk patients with or without diabetes, but important risk factorDiabetes also substantially increases the risk of CVD.In individuals with type 2 diabetes, the most common pattern of dyslipidemia includes increased triglyceride levels and decreased levels of high-density lipoprotein cholesterol (HDL).Although mean concentrations of LDL are similar in those with and without diabetes, certain qualitative changes in LDL have been noted, particularly a higher proportion of smaller and denser LDL particles that are more susceptible to oxidation and, thus, are more atherogenic.Reference:Haffner SM. Dyslipidemia management in adults with diabetes. Diabetes Care. 2004;27(suppl 1):S68-S71.Haffner SM. Diabetes Care. 2004;27(suppl 1):S68-S71.
25 Prevalence of Dyslipidemia in Patients With Type 2 Diabetes Affected (%)Results from a national population-based survey that included data from the National Health and Nutrition Examination Surveys conducted from 1988 to 1994 and 1999 to 2002, as well as data from 1995 and 2002 from the Behavioral Risk Factor Surveillance System, indicate the prevalence of lipid abnormalities in patients with type 2 diabetes.The most recent data suggest that dyslipidemia is still a common feature of type 2 diabetes. More than 50% of the individuals displayed elevations in total cholesterol (total C) and/or triglycerides. In addition, 66% of the individuals in the survey had LDL levels that were 100 mg/dL or higher.Reference:Saaddine JB, Cadwell B, Gregg EW, et al. Improvements in diabetes processes of care and intermediate outcomes: United States, Ann Intern Med. 2006;144:Total C≥200 mg/dLLDL-C≥100 mg/dLHDL-C<40 mg/dLTriglycerides≥150 mg/dLC: cholesterolSaaddine JB, et al. Ann Intern Med. 2006;144:
26 American Diabetes Association Lipid Treatment Goals Diabetes without overt CVDDiabetes with overt CVDLDL <100 mg/dL30%-40% reduction with statin for patients >40 years,regardless of baseline LDLLDL <70 mg/dL an option30%-40% reduction with statin therapy for all patientsThe American Diabetes Association (ADA) advocates lifestyle changes, including dietary modification and increases in physical activity, for individuals with type 2 diabetes and dyslipidemia.For individuals without overt CVD, the ADA recommends lowering LDL to less than 100 mg/dL as a primary goal. In addition, for individuals older than 40 years, statin therapy is advocated to achieve an LDL reduction of 30% to 40% regardless of baseline LDL levels.For individuals with overt CVD, an LDL goal of less than 70 mg/dL is recommended as an option. Individuals with overt CVD, regardless of age, should be treated with statins to decrease LDL by 30% to 40%.For all individuals with type 2 diabetes and dyslipidemia, the ADA recommends that triglyceride levels be kept at less than 150 mg/dL and HDL levels at higher than 40 mg/dL in men and 50 mg/dL in women.Reference:American Diabetes Association. Standards of medical care in diabetes – Diabetes Care. 2006;29(suppl 1):S4-S42.Decrease triglycerides to <150 mg/dLIncrease HDL to >40 mg/dL in men and >50 mg/dL in womenAmerican Diabetes Association. Diabetes Care. 2006;29(suppl 1):S4-S42.
27 Therapeutic Lifestyle Changes Adherence to 5 healthful lifestyles reduced coronary events by ≈62% in 16 yearsLifestyle changes reduced coronary events by 57% in men taking medications for HTN or dyslipidemiaMen who adopted 2 lifestyle changes had 27% lower risk than those who did notLIFESTYLE CHANGESEliminate tobacco exposureBody mass index <25 kg/m230 min/d physical activityLimit alcohol use to 1-2 drinks/dTop 40% of healthy diet scoreThe lifestyle study by Chiuve et al1 raised several important points:Lifestyle predicted 60% of all CVD events during a 16-year period in a cohort of 51,529 US male health professionals.Thus, all recommendations for hypercholesterolemia should include the following lifestyle factors:Eliminate exposure to tobacco (smoking and secondhand smoke)*Maintain body mass index (BMI) at less than 25 kg/m2Engage in 30 minutes per day of moderate to vigorous physical activityConsume alcohol in moderate amounts (5-30 g/d) if you choose to drinkTry to be in the top 40% of healthy diet scoreWhether or not a medication is prescribed, adherence to a healthful lifestyle still provides benefits over time.*In the INTERHEART case-control study, Teo et al2 found the following:Smoking raises the risk of acute myocardial infarction (AMI) by 300% (5.6% per cigarette)Secondhand smoke raises the risk of AMI by 24% to 62% (dose response)Chewing tobacco increases the risk of AMI by 223%References:Chiuve SE, McCullough ML, Sacks FM, et al. Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and anti-hypertensive medications. Circulation. 2006;114:Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006;368:HTN: hypertensionChiuve SE, et al. Circulation. 2006;114:
28 Lifestyle Modifications Physical activityGet regular exerciseReduce “screen time”; increase daily activityAvoidance of tobaccoWeight controlTrack weight and caloric intakeReduce food portion sizeHealthful dietRegular physical activity is recommended to reduce CVD risk.At least 30 cumulative minutes of physical activity on most days of the week is recommended for all adults.At least 60 minutes of physical activity on most days of the week is recommended for adults who are trying to lose weight or maintain weight loss, and for children.Reduce sedentary activities such as “screen time” (watching TV, surfing the Web, playing computer or video games) and make daily choices to move rather than be moved (eg, take the stairs instead of the elevator).Avoid the use of tobacco and exposure to tobacco smoke.Weight control requires that energy intake be balanced with energy expenditure.Track actual weight and compare with a healthy weight goal.Be aware of the calorie content of foods.Control portion sizes.Weight loss requires regular physical activity along with calorie restriction.Do the following for a healthful diet:Eat plenty of fruits and vegetables.Eat plenty of whole-grain, high-fiber foods.Consume fish at least twice a week.Limit salt intake.If you choose to consume alcohol, do so in moderation (eg, 1 drink per day for women).Limit your intake of saturated fat, trans fat, and cholesterol.Reference:Lichtenstein AH, Appel LJ, Brands M, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114:82-96.Lichtenstein AH, et al. Circulation. 2006;114:82-96.
29 Dietary Modifications Improve Lipid Profiles Limit intake of saturated fat, trans fat, and cholesterol1Choose lean meats, fish, and vegetable alternativesChoose fat-free and low-fat dairy productsLimit intake of partially hydrogenated fatsDietary changes can significantly decrease LDL2Limit intake of saturated fat, trans fat, and cholesterol.1Major sources of saturated fats are animal fats (meat, dairy).Major sources of trans fats are partially hydrogenated fats used in commercial food preparation of fried and baked products.Major sources of cholesterol in the diet are animal products (meat, dairy, eggs).To limit intake of saturated fat, trans fat, and cholesterol, do the following:1Choose lean meats and vegetable alternatives.Choose fat-free and low-fat dairy products.Limit intake of partially hydrogenated fats.Dietary changes can have impressive effects and significantly decrease LDL levels.2References:Lichtenstein AH, Appel LJ, Brands M, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114:82-96.Appel LJ, Sacks FM, Carey VJ, et al; OmniHeart Collaborative Research Group. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005;294:Lichtenstein AH, et al. Circulation. 2006;114:82-96.Appel LJ, et al. JAMA. 2005;294:
30 Effects of Three Healthful Diets* on LDL Levels All (n = 161)Baseline mean = mg/dLLDL ≥130 mg/dL (n = 75) Baseline mean = mg/dLCARB PROT UNSAT CARB PROT UNSAT-5-10mg/dLmg/dL-15-20This slide shows results from the OmniHeart Randomized Trial in adults with prehypertension or stage 1 hypertension. Each dietary period lasted 6 weeks, and body weight was kept constant.Three healthful diets low in saturated fat, trans fat, and cholesterol were used:A diet rich in carbohydrates, similar to the DASH diet (Dietary Approaches to Stop Hypertension)A diet rich in protein (about half from plant sources)A diet rich in unsaturated fat (predominantly monounsaturated fat)The results were impressive:Diets with reduced saturated fats were associated with LDL decreases of 12 to 14 mg/dL (bar graph on left).Even more impressive LDL decreases of 20 to 24 mg/dL were seen among the patients who started out with high LDL levels (pretreatment LDL of 130 mg/dL or higher; bar graph on right).Reference:Appel LJ, Sacks FM, Carey VJ, et al; OmniHeart Collaborative Research Group. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005;294:-25*Each diet: 6% saturated fat; <150 mg/d cholesterol; no trans fat.Appel LJ, et al. JAMA. 2005;294:
31 ? Key Question What is your next step if lifestyle changes don’t decrease lipid levels to goal?Use a bile acid sequestrantUse a fibrateUse a statinUse niacin (nicotinic acid)Use ezetimibeUse your keypad to vote now!The correct answer is 3.
32 MRC/BHF Heart Protection Study Major Coronary EventsCoronary MortalityNonfatal MIStrokeMajor Vascular Events (%)Reduction ofThe MRC/BHF Heart Protection Study of high-risk patients found that simvastatin (40 mg/d) decreased LDL levels by about 39 mg/dL (compared with the placebo group) and produced a significant 18% reduction in the coronary death rate (also compared with placebo).The simvastatin group also had a 38% proportional reduction in first nonfatal myocardial infarction (MI), a 27% reduction in major coronary events (nonfatal MI or coronary death), and a 25% reduction in the incidence of stroke.Similar (and significant) benefits were seen even among patients with normal baseline LDL levels.These findings support the use of statins in all high-risk patients, regardless of baseline LDL levels.Reference:Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.MI: myocardial infarctionMRC/BHF: Medical Research Council/British Heart FoundationHeart Protection Study Collaborative Group. Lancet. 2002;360:7-22.
33 Major Vascular Events (%) ASCOT-LLA TrialNonfatal MI+Fatal CHDTotal Coronary EventsTotal CV EventsStrokeMajor Vascular Events (%)Reduction ofThe ASCOT-LLA Trial showed that treatment of hypertensive patients with atorvastatin (10 mg/d) decreased LDL levels by 29% from a baseline of 133 mg/dL. Note that these patients had only borderline-increased LDL levels at baseline.This produced a 36% reduction (compared with the placebo group) in the risk of nonfatal MI and fatal CHD.This also resulted in a 21% reduction in total cardiovascular events (including revascularization procedures), a 29% decrease in total coronary events, and a 27% reduction in stroke.Thus, lowering LDL levels—even among patients not considered dyslipidemic—can aid in the primary prevention of CHD and reduce major cardiovascular events.Reference:Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361:ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering ArmSever PS, et al. Lancet. 2003;361:
34 ASTEROID TrialIntravascular ultrasound (IVUS) was used to assess coronary atherosclerosisRosuvastatin (40 mg/d) for 24 months decreased LDL by 53% and increased HDL by 15%Significant regression of atherosclerosis was seenThe ASTEROID Trial used intravascular ultrasound (IVUS) to assess coronary atherosclerosis in statin-naive patients. Use of rosuvastatin (40 mg/d) for 24 months significantly decreased LDL by 53% (from 130 mg/dL to 61 mg/dL) and significantly increased HDL by 15% (from 43 mg/dL to 49 mg/dL). This was accompanied by significant regression of atherosclerosis, as determined by 3 IVUS-derived measures.Thus, treatment to achieve LDL levels below current guidelines—accompanied by significant increases in HDL—can cause regression of atherosclerosis in patients with coronary disease.Reference:Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:ASTEROID: A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma BurdenNissen SE, et al. JAMA. 2006;295:
35 Cholesterol Treatment Trialists’ (CTT) Meta-Analysis Major Vascular EventsAll-Cause MortalityCoronary MortalityStrokeReduction in Incidence ( %)In a meta-analysis by the Cholesterol Treatment Trialists’ (CTT) Collaborators of 14 randomized trials of statins involving more than 90,000 participants, patients treated with statins had LDL levels that were 14 to 68 mg/dL lower than those in patients who did not receive statins.The results showed a 12% decrease in all-cause mortality and a 21% reduction in major vascular events (such as MI, stroke, or coronary death) for each 39-mg/dL decrease in LDL levels.A 19% decrease in coronary mortality and a 17% reduction in stroke were found for each 39-mg/dL decrease in LDL levels.These beneficial effects were significant in the first year and even greater in subsequent years.Full adherence to statin regimens can result in LDL reductions of 58 mg/dL or more, resulting in a one-third reduction in the incidence of major vascular events.Thus, statin therapy can reduce the incidence of major vascular events regardless of the patient’s initial lipid levels, and prolonged statin treatment to maintain substantial LDL reductions should be considered in all patients at high risk of major vascular events.Reference:Baigent C, Keech A, Kearney PM, et al; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:Baigent C, et al. Lancet. 2005;366:
36 MERCURY II TrialMore high-risk patients reached their LDL target of <100 mg/dL with rosuvastatin (10 or 20 mg/d) than with atorvastatin (10 or 20 mg/d) or simvastatin (20 or 40 mg/d)Likewise, more patients at very high risk reached their LDL goal of <70 mg/dL with rosuvastatin than with atorvastatin or simvastatinThe MERCURY II Trial found that among high-risk patients with an LDL target of less than 100 mg/dL, more patients achieved their LDL target with rosuvastatin (10 or 20 mg/d) than with atorvastatin (10 or 20 mg/d) or simvastatin (20 or 40 mg/d). Likewise, among very high-risk patients with an LDL target of less than 70 mg/dL, more patients reached the goal with rosuvastatin than with atorvastatin or simvastatin.Thus, switching to a more effective statin may enable high-risk and very high-risk patients to achieve their lipid targets.Reference:Ballantyne CM, Bertolami M, Hernandez Garcia HR, et al. Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II. Am Heart J. 2006;151:975.e1-975.e9.MERCURY II: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapYBallantyne CM, et al. Am Heart J. 2006;151:975.e1-975.e9.
37 Other Lipid-Lowering Drugs Fibrates can decrease triglycerides and increase HDL levels1-3Niacin (nicotinic acid) can also decrease triglycerides and increase HDL levels1-3Ezetimibe can further decrease LDL levels by selectively inhibiting intestinal absorption of cholesterol1,3Bile acid sequestrants may decrease LDL1-3Combination therapy may be effective1,3After statins, the second line of drug therapy may include the following:Fibrates (eg, gemfibrozil, fenofibrate) decrease triglycerides and increase HDL.1-3Niacin (nicotinic acid) also decreases triglycerides and increases HDL.1-3A selective inhibitor of cholesterol absorption in the intestine, ezetimibe does the following1,3:Inhibits intestinal absorption of both dietary and biliary cholesterolDecreases levels of LDLHas additive effects with statinsBile acid sequestrants (eg, cholestyramine, colestipol, colesevelam) do the following1-3:Bind bile acids in the intestinal lumenDecrease LDL and increase HDLMay increase triglycerides in patients who already have increased triglyceridesCombination therapy (usually a statin plus another lipid-lowering drug) may be effective1,3:Especially useful in high-risk patients with low LDL goals, when a statin alone does not decrease LDL to goalMay also allow the use of relatively low drug doses, thus reducing the risk of adverse effectsReferences:Drugs for lipids. Treat Guidel Med Lett. 2005;3:15-22.Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:1. Treat Guidel Med Lett. 2005;3:15-22.2. NCEP ATP III. JAMA. 2001;285:3. Grundy SM, et al. Circulation. 2004;110:
38 NCEP ATP III Drug Therapy Progression 6 wk6 wk4-6 moIf goal not met, intensify drug therapy or refer to lipid specialistContinue to monitor response and adherenceBegin drug therapy to decrease LDLIf goal not met, intensify drug therapyThe Executive Summary of the NCEP ATP III report suggests a general timeline for managing drug therapy for increased LDL levels.If therapeutic lifestyle changes have failed to achieve treatment goals, drug therapy should begin. However, therapeutic lifestyle changes should not be abandoned, but should be continued, with drug therapy added as an adjunct.Drug therapy typically begins with a statin at a moderate dose, but nicotinic acid or a bile acid sequestrant can be used instead.Recheck lipid levels after about 6 weeks.If treatment goals are still not met, the statin dose may be increased or combination therapy (combining the statin with a second lipid-lowering drug) may be used.Recheck lipid levels again after about 6 weeks.If lipid goals are still not met, consider further intensifying drug therapy or consulting with a lipid specialist.When the LDL goal has been met, consider treating other lipid risk factors and nonlipid risk factors. Continue to monitor the patient’s response to therapy every 4 to 6 months.Reference:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:NCEP ATP III. JAMA. 2001;285:
39 Improving Patients’ Adherence Simplify medication regimensPrescribe fewer pills per day1Avoid medication switching2Help patients remember to take medicationsTime pills with events like meals, bedtime3Recommend pill boxes, personal alarmsTeach patients about risks and benefitsOffer educational tools, brochures, Web sitesUse follow-up lipid tests to monitor progress4One barrier to adherence is a complex medication regimen that is hard to recall and to implement.As a rule, it is easier to remember to take fewer rather than more pills per day. A meta-analysis of 8 studies with 11,485 observations found that average adherence to once-daily dosing was 91%, which was significantly higher than adherence to multiple daily dosing.1Further, a retrospective cohort analysis found that even a switch from one statin to another significantly reduced medication adherence among 38,866 adults who were new statin users.2Forgetting to take medications is a barrier.Prescribe pill taking by events (eg, meals, bedtime) rather than time of day. Older adults in one study preferred event-based (eg, mealtime or bedtime) rather than time-based (eg, 7:00 AM) instructions for prescription drug administration.3Consider multicompartment pill boxes.Suggest a personal alarm to help establish the habit.Lack of knowledge of the disease state and why treatment is needed is another barrier to adherence. Knowledge is also a motivator for adherence.Dyslipidemia is a complex topic to understand and causes no symptoms (thus is easy to deny or forget), so educational interventions should be helpful.A retrospective analysis of 19,422 managed care enrollees taking statins found that those who had follow-up lipid tests or extra MD visits about their dyslipidemia were substantially more likely to be adherent. Patients who received both interventions were 45% more likely to have taken their statin appropriately.4Urge patients to call about adverse effects before stopping a medication.Explore “awkward” symptoms (eg, sexual dysfunction and incontinence).References:Iskedjian M, Einarson TR, MacKeigan LD, et al. Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis. Clin Ther. 2002;24:Thiebaud P, Patel BV, Nichol MB, Berenbeim DM. The effect of switching on compliance and persistence: the case of statin treatment. Am J Manag Care. 2005;11:Branin JJ. The role of memory strategies in medication adherence among the elderly. Home Health Care Serv Q. 2001;20:1-16.Benner JS, Tierce JC, Ballantyne CM, et al. Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy. Pharmacoeconomics. 2004;22(suppl 3):13-23.1. Iskedjian M, et al. Clin Ther. 2002;24:2. Thiebaud P, et al. Am J Manag Care. 2005;11:3. Branin JJ. Home Health Care Serv Q. 2001;20:1-16.4. Benner JS, et al. Pharmacoeconomics. 2004;22(suppl 3):13-23.
40 Improving Patients’ Adherence Medication adherence drops as costs rise1Ask if patients have prescription drug coverageIdentify generic or preferred drugsUrge patients to raise cost problems over timeDepression can reduce adherence2Look for and ask about signs of depressionTreat and/or refer depressed patients for counselingDrug cost can be a tremendous barrier for patients with low incomes and/or poor drug coverage. Even among those who have Medicare Part D, patients with high drug costs are likely to find themselves in the “doughnut hole” at some point during the year, which may reduce their adherence.An analysis of 7532 pharmacy claims for 6 drug classes from a large health plan found that the proportion of days covered by prescription products was better among patients who were prescribed generic drugs (62% or higher adherence) or preferred drugs (30% higher) versus nonpreferred ones that cost them more out of pocket.1Regardless of whether depression is the primary chronic illness being treated, its presence can be an independent barrier to medication adherence. Among patients taking cholesterol-lowering drugs for 6 months, medication adherence (measured with electronic pill caps) was significantly reduced in depressed patients.2References:Shrank WH, Hoang T, Ettner SL, et al. The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions. Arch Intern Med. 2006;166:Stilley CS, Sereika S, Muldoon MF, et al. Psychological and cognitive function: predictors of adherence with cholesterol lowering treatment. Ann Behav Med. 2004;27:1. Shrank WH, et al. Arch Intern Med. 2006;166:2. Stilley CS, et al. Ann Behav Med. 2004;27:
41 Share Decision MakingA patient-clinician partnership based on mutual respect and trust improves medication adherenceAsk patients how they understand their condition and the need to treat itListen and probe for perceived barriersCustomize your suggestions to their needsEnlist family members as advocatesA trusting relationship between patient and clinician has been found to attenuate cost issues.Among individuals with diabetes stratified into a “high-trust” and a “low-trust” group, low-trust patients with higher out-of-pocket costs were more likely to omit taking their prescription medications.Reference:Piette JD, Heisler M, Krein S, Kerr EA. The role of patient-physician trust in moderating medication nonadherence due to cost pressures. Arch Intern Med. 2005;165:Piette JD, et al. Arch Intern Med. 2005;165:
43 Case Study 76-year-old white nonsmoking woman History of hypertension, depressionCurrent medications:Diltiazem 240 mg qdNefazodone 150 mg bidExamination: Height 5′6″; weight 146 lb; BMI 23.6 kg/m2; BP 139/82 mm Hg; pulse 72 bpmOur case is a 76-year-old white woman who is a nonsmoker.She has a history of hypertension and depression.Her current medications include a calcium-channel blocker (diltiazem, 240 mg/d) and a selective serotonin reuptake inhibitor (SSRI; nefazodone, 150 mg twice daily).Physical examination was unremarkable. Her BMI is within the normal range. Her blood pressure is in the borderline or prehypertension range with an antihypertensive medication (diltiazem).BMI: body mass index
44 Laboratory Results Creatinine: 1.4 mg/dL Lipid panel Total cholesterol: 245 mg/dLLDL: 156 mg/dLHDL: 59 mg/dLTriglycerides: 148 mg/dLHer creatinine is 1.4 mg/dL, with an estimated glomerular filtration rate of 39 mL/min/1.73 m2, indicating a moderate decrease in renal function.Her total cholesterol is high, her LDL is borderline high, and her HDL and triglycerides are within normal limits.Consider her decreased renal function when determining appropriate drug therapy.Her renal and hepatic function should be monitored on a regular basis.
45 ATP III: Framingham Point Scores to Estimate 10-Year Risk AgePointsSBP mm HgIf UntreatedIf TreatedAgeAge 40-49Age 50-59Age 60-69Age 70-7920-3435-3940-4445-4950-5455-5960-6465-6970-7475-79-7-336810121416<12016012343456NonsmokerSmoker97421AgeTotal CHDL-CSystolic BP (SBP)Smoking statusPoint totalPoint Total10-Year Risk, %<9910111213141516171819202122232425<11234568111417222730HDL mg/dLPoints6050-5940-49<40-112Total CholesterolAt its website,1 the NCEP offers a risk-assessment tool for estimating the 10-year risk. This tool uses data from the Framingham Heart Study to estimate the 10-year risk of “hard” CHD outcomes (MI and coronary death). It is designed to estimate risk in adults aged 20 years and older who do not have heart disease or diabetes.Calculators to estimate 10-year risk are available for handheld devices and on the NCEP website (http://www.nhlbi.nih.gov/guidelines/cholesterol).Total cholesterol: Total cholesterol values should be the average of at least 2 measurements obtained from lipoprotein analysis.HDL cholesterol: HDL values should be the average of at least 2 measurements obtained from lipoprotein analysis.Smoker: The designation “smoker” means any cigarette smoking in the past month.Systolic blood pressure (SBP): The value used is that obtained at the time of assessment, regardless of whether the person is taking antihypertensive therapy. (Treated hypertension carries a residual risk.)Note: The 10-year (short-term) risk of developing CHD is determined using Framingham risk scoring. The risk factors included in the Framingham calculation are age, total cholesterol, HDL, SBP, treatment for hypertension, and cigarette smoking. Because of a larger database, Framingham estimates are more robust for total cholesterol than for LDL. Note, however, that LDL remains the primary target of therapy.1Using the online calculator, and according to the patient’s age, total cholesterol and HDL levels, SBP, and smoking status, she has a Framingham 10-year risk of 17%.2References:Risk assessment tool for estimating 10-year risk of developing hard CHD (myocardial infarction and coronary death). Available at: Accessed on December 7, 2006.Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:AgeAge 40-49Age 50-59Age 60-69Age 70-79<160280481113368102457123412NCEP ATP III. JAMA. 2001;285:
46 ? Decision Point What is this patient’s risk category? High Moderately highModerateEither moderate or moderately highLowerUse your keypad to vote now!The correct answer is 2.Her Framingham 10-year risk score is 17%, and she has 2 or more risk factors (hypertension and age; family history of premature CHD is unknown).
47 Therapeutic Considerations Therapeutic lifestyle changesFirst line of treatmentInclude dietary modification, exercise, and weight controlLipid-lowering medications1,2Statins are safe and effective,3-5 and significantly reduce risk of CVD and stroke6-8Other agents (eg, fibrates, niacin)9Lifestyle modification is the first line of treatment.Therapeutic lifestyle changes include dietary modification, exercise, and weight loss.However, compliance with lifestyle modifications can be difficult to achieve and sustain, particularly in elderly patients with comorbid conditions that limit physical activities.Therefore, lifestyle modification is best used in combination with pharmacologic lipid-lowering therapy. The 2004 update to the NCEP guidelines for cholesterol management suggests that lipid-lowering therapy be strongly considered in older patients at risk of MI.1,2Studies show that statins are a safe and effective first-line therapy in elderly patients,3-5 resulting in significant cardiovascular risk reduction.6-8Other lipid-lowering agents such as fibrates and niacin may also be of benefit, although significant reductions in overall mortality have yet to be demonstrated.9References:Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:Stone NJ, Bilek S, Rosenbaum S. Recent National Cholesterol Education Program Adult Treatment Panel III update: adjustments and options. Am J Cardiol. 2005;96:53E-59E.Deedwania P, Volkova N. Dyslipidemia and lipid-lowering therapy in the elderly. Expert Rev Cardiovasc Ther. 2005;3:Helmy T, Patel AD, Alameddine F, Wenger NK. Management strategies of dyslipidemia in the elderly: MedGenMed. 2005;7:8.Pohlel K, Grow P, Helmy T, Wenger NK. Treating dyslipidemia in the elderly. Curr Opin Lipidol. 2006;17:54-57.Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341:1. Grundy SM, et al. Circulation. 2004;110:2. Stone NJ, et al. Am J Cardiol. 2005;96:53E-59E.3. Deedwania P, Volkova N. Expert Rev CardiovascTher. 2005;3:4. Helmy T, et al. MedGenMed. 2005;7:8.5. Pohlel K, et al. Curr Opin Lipidol. 2006;17:54-57.6. NCEP ATP III. JAMA. 2001;285:7. Heart Protection Study Collaborative Group.Lancet. 2002;360:7-22.8. Shepherd J, et al. Lancet. 2002;360:9. Rubins HB, et al. N Engl J Med. 1999;341:
48 Therapeutic Considerations Drug interactionsCalcium channel blockers1Antidepressants2Others (eg, warfarin)3Comorbid conditionsRegular monitoring of hepatic, renal functionDecreased renal functionCheck for potential drug interactions, such as those associated with the following agents:Calcium channel blockers (especially diltiazem) that inhibit certain cytochrome P450 isoenzymes1Antidepressant medications that inhibit certain cytochrome P450 isoenzymes2Nefazodone (an SSRI) is a potent inhibitor of the same P450 isoenzymes involved in the metabolism of some statins (especially atorvastatin, lovastatin, and simvastatin)2A number of other drugs inhibit cytochrome P450 enzymes and thus increase plasma statin levels, requiring a reduction in statin dosage to avoid toxicity (eg, rhabdomyolysis). The effects of other drugs, such as warfarin, may be enhanced if used with a statin.3Consider any comorbid conditions.Elderly patients taking statins should receive regular monitoring of renal and hepatic function.The lowest dose that is effective should be used.This patient has a moderate decrease in renal function (creatinine = 1.4 mg/dL), which may affect the excretion of certain medications.References:Herman RJ. Drug interactions and the statins. CMAJ. 1999;161:Karnik NS, Maldonado JR. Antidepressant and statin interactions: a review and case report of simvastatin and nefazodone-induced rhabdomyolysis and transaminitis. Psychosomatics. 2005;46:Drugs for lipids. Treat Guidel Med Lett. 2005;3:15-22.1. Herman RJ. CMAJ. 1999;161:2. Karnik NS, Maldonado JR. Psychosomatics. 2005;46:3. Treat Guidel Med Lett. 2005;3:15-22.
49 Special Populations Women1 CHD delayed 10 to 15 years versus men Premature CHD risk associated with multiple risk factors and metabolic syndromeTreatment approach should be similar for women and menAfrican Americans1Highest overall CHD mortality rateAsian Indians2,3Increased risk of metabolic syndrome and CHD versus whitesCompared with men, women have a later onset of CHD by at least a decade.Most premature CHD in women results from the presence of multiple risk factors and metabolic syndrome.The NCEP ATP III guidelines advocate a similar approach to primary and secondary prevention in men and women.1However, many of the studies of lipid-lowering therapy were done in populations consisting of 70% to 80% male subjects. Further studies are needed to evaluate the results in women.African Americans display the highest risk of CHD and the highest out-of-hospital coronary death rates among ethnic groups in the United States.1Asian Indians have a higher incidence of hyperinsulinemia and insulin resistance and display an obesity phenotype that, together, may increase the risk of CHD.2,3Other ethnic groups in the United States vary somewhat in CHD risk, but the increased risk in any one group was not sufficient to compel the NCEP to modify their guidelines for cholesterol management.1References:Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:Misra A, Vikram NK. Insulin resistance syndrome (metabolic syndrome) and Asian Indians. Curr Sci. 2002;83:Enas EA, Garg A, Davidson MA, et al. Coronary heart disease and its risk factors in first-generation immigrant Asian Indians to the United States of America. Indian Heart J. 1996;48:1. NCEP ATP III. JAMA. 2001;285:2. Misra A, Vikram NK. Curr Sci. 2002;83:3. Enas EA, et al. Indian Heart J. 1996;48:
50 ConclusionsImproving patients’ adherence will improve clinical outcomesOptimal results require both lifestyle and medical interventionsLipid-lowering therapy must be tailored to the individual patientRisk determines lipid goalsComorbid conditions influence treatmentFindings from recent clinical trials highlight the importance of improving patients’ adherence, which subsequently improves clinical outcomes.Optimal results depend on more than just reaching lipid-level targets; adherence to lifestyle and medical interventions can help prevent MI and stroke.Nurse practitioners and physician assistants are in an ideal position to educate patients about their individual treatment goals, foster strong patient-provider relationships, monitor patients’ progress, and encourage continued adherence to measures for primary and secondary prevention of CVD.Lipid-lowering therapy must be tailored to each patient.The level of CVD risk influences lipid targets.Comorbid conditions influence medication selection.Primary care clinicians must consider these patient-specific differences to improve outcomes.Given the growing numbers of the elderly population, it is critical that primary care clinicians recognize and appropriately treat dyslipidemia in this population.
52 PCE Takeaways Use risk calculation tools Identify appropriate goals based on risk… and treat to goal!Appreciate the unique profile of diabetic patients with dyslipidemiaAddress common barriers to adherence and modify treatment regimen accordingly
53 ? Key Question How important are the IVUS data when conveying information linking medicaltreatment to atherosclerosis regressionto patients?Extremely importantVery importantSomewhat importantNot very importantUse your keypad to vote now!The correct answer is 3.