43401 - INCREASING GLOBAL BURDEN OF CARDIOVASCULAR DISEASE:...

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Unformatted text preview: INCREASING GLOBAL BURDEN OF CARDIOVASCULAR DISEASE: CONTRIBUTIONS OF METABOLIC SYNDROME METABOLIC Charles H. Hennekens, MD Sir Richard Doll Research Professor of Medicine Charles E. Schmidt College of Medicine Florida Atlantic University (FAU) Clinical Professor of Preventive Medicine Nova Southeastern University Voluntary Professor of Family Medicine and Community Health University of Miami Miller School of Medicine (UMMSM) Disclosure Disclosure •I am funded by the Charles E. Schmidt College of Medicine at Florida Atlantic University (FAU). I have served as Principal Investigator on two investigator initiated research grants funded to FAU by Bayer testing the effects of aspirin dose on platelet and inflammatory biomarkers as well as nitric oxide formation. on serve •I serve as an independent scientist in an advisory role to investigators and sponsors as Chair of Data and Safety Monitoring Boards for Actelion, Amgen, Anthera, Bristol-Myers Squibb, and Sunovion and as a Member of Data and Safety Monitoring Boards for AstraZeneca, Bayer , British Heart Foundation, Canadian Institutes of Health Research and Lilly. serve •I serve as an independent scientist in an advisory role to the U.S. Food and Drug Administration, U.S. National Institutes of Health, Children's Services Council of Palm Beach County and UpToDate. Palm serve •I serve as an independent scientist in an advisory role to legal counsel for GlaxoSmithKline and Stryker. serve •I serve as speaker for the Association for Research in Vision and Ophthalmology, Baptist Health South Florida, National Association for Continuing Education, PriMed, and the International Atherosclerosis Society. PriMed, •I receive royalties for authorship or editorship of three textbooks. receive •I receive royalties as co-inventor on patents concerning inflammatory markers and cardiovascular disease which are held by Brigham and Women’s Hospital. and have •I have an investment management relationship with The West-Bacon Group within SunTrust Investment Services who has discretionary investment authority. within do •I do not own any common or preferred stock in any pharmaceutical or medical device company. LIFE EXPECTANCY AT BIRTH LIFE • US AND RICH COUNTRIES: 77 YEARS (73 US IN MEN AND 81 IN WOMEN IN • POOR COUNTRIES: 50 YEARS (46 IN MEN POOR AND 54 IN WOMEN) AND Heart Disease In The United States Heart • Chief cause of death among men age 45 years Chief and older and • Chief cause of death among women age 65 Chief years and older years • Responsible for 1 in 3 deaths in men and Responsible women, or ~750,000 fatalities each year women, Change In Age-Adjusted Mortality Change 1979 - 1995 10 Noncardiovascular Disease 0 -10 % Decline -20 Coronary Heart Disease -30 Stroke -40 -50 -60 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 National Center for Health Statistics. Postulated Reasons For Decreasing CHD Mortality Decreasing Treatment of Acute MI ∀ ↓ in case fatality rate (30% → 5%-10%) for hospitalized MI hospitalized ∀ ↑ in utilization of: in vaspirin vthrombolytics vβ-blockers vACE inhibitors Hennekens. Circulation. 1998;97:1095. Postulated Reasons For Decreasing CHD Mortality Decreasing Secondary prevention after MI Secondary • • Therapeutic Lifestyle Changes (TLC) Increase in utilization of: – aspirin β-blockers – ACE inhibitors – Statins (HMG-CoA reductase inhibitors) Postulated Reasons For Decreasing CHD Mortality Decreasing Primary prevention ∀ ↓ in smoking(>50% → <25%) ∀ ↑ in treatment of hypertension(16% → 55%) ∀ ↑ in treatment of hypercholesterolemia (target 230 → 200) Hennekens. Circulation. 1998;97:1095. Trends Among US Adolescents Trends Cigarette smoking Body mass index Physical Inactivity Type II diabetes Hennekens. Circulation. 1998;97:1095. Shifting Worldwide Burden Of Disease Shifting 1990 All Other 25.5% 2020 Cancer 11.9% All Other 33.2% Cancer 18.0% CVD 28.4% Communicable, Perinatal, Nutritional 34.2% Communicable, Perinatal, Nutritional 15.1% Murray and Lopez. The Global Burden of Disease. 1996. CVD 33.7% Increasing Worldwide Burden Increasing Of Cardiovascular Disease 1990 2020 Years Of Life Lost 4th 1st Premature Death And Disability 5th 1st Conclusion Conclusion Based on these considerations the World Based Health Organization has projected that within the next decade cardiovascular disease will be the leading cause of death and disability in the world world Reasons For Worldwide Increase Reasons In Cardiovascular Disease Malnutrition Infection Smoking BMI Metabolic Syndrome Any 3 of the Following 5 Criteria • Obesity – • High density lipoprotein cholesterol (HDL-C) – • • Waist greater than 40 inches in men or 35 inches in women 35 Less than 40 mg/dL in men 50 mg/dL in women 50 Triglycerides greater than 150 mg/dL Blood pressure greater than 130 mm Hg systolic or Blood 85 mm Hg diastolic greater than 110 mg/dL • Fasting blood glucose and Treatment of High Blood Cholesterol in Expert Panel on Detection, Evaluation, Adults. JAMA. 2001;285:2486-2497. Metabolic Syndrome Metabolic • “The U.S. is the fattest society in the world and likely The to be the fattest in the history of the world”. (CH Hennekens, NY Times 1/1/99) Hennekens, • Obesity is associated with dyslipidemia, Obesity hypertension, and insulin resistance which has been termed metabolic syndrome. termed • In the U.S. 40% of adults aged 40 and older have In metabolic syndrome. metabolic • Patients with metabolic syndrome have a 10 year risk Patients of a first CHD event of 16-18%. of Importance of Assessing Multiple Risk Factors for CHD Factors + Hypertension + Hyperglycemia CHD Risk per 100 (10 y) 30 + Low HDL-C No other RF + Smoking 25 20 15 10 5 0 <100 100-129 130-159 160-189 LDL cholesterol (mg/dL) ≥190 Prevalence of the Prevalence Metabolic Syndrome by Race Metabolic 40 35 White African American Hispanic Other Prevalence (%) 30 25 20 15 10 5 0 Men Women Data presented as % (SE) Adapted from: Ford ES. JAMA. 2002;287:356-359. New-onset Diabetes, A CHD Risk Equivalent, as New-onset Correlated With the Number of Characteristics of the Metabolic Syndrome of 14 No. of MetS risk factors: 4/5 3 2 1 0 12 % With event 10 RR 24.4 8 6 7.26 4 4.50 2.36 2 1.00 0 0 1 2 3 Years 4 5 6 RR: Relative risk Adapted from: Sattar N, et al. Circulation. 2003;108:414-419. Modifiable CV Risk Factors in Modifiable Patients with Type 2 Diabetes*: Patients Results from UKPDS 23 Results Position Variable P Value† First LDL–C <0.0001 Second HDL–C 0.0001 Third A1c 0.0022 Fourth Systolic BP 0.0065 Fifth Smoking 0.056 CV = cardiovascular. *Adjusted for age and gender in 2693 Caucasian patients with type 2 diabetes, with dependent variable as time to first *Adjusted event. event. †Significant for coronary artery disease (n = 280). P values are significance of risk factor after controlling for all other risk Significant factors in model. factors Adapted from Turner RC et al. BMJ. 1998;316:823–828 Adapted BMJ Diabetes and Cardiovascular Disease Diabetes • • • Diabetes is a major risk factor for CVD and can be a Diabetes component to the metabolic syndrome which markedly increases risks of CVD markedly The CARDS trial of diabetics in primary prevention The was terminated early due to a statistically extreme 37% reduction in the primary pre-specified outcome 37% The US National Cholesterol Education Program The (NCEP) III has elevated diabetes from a major risk factor to a CHD risk equivalent and recommends that all patients with diabetes should be treated as aggressively as survivors of a CVD event (i.e., MI or stroke). stroke). COMETS: Rosuvastatin Has a Better Effect on the COMETS: Overall Lipid Panel Than Does Atorvastatin in Patients With Metabolic Syndrome Patients LSM Change From Baseline (%) (SE) 6 Weeks 12 Weeks Placebo (n=78) RSV RSV 10 mg 10 (n=164) ATV ATV 10 mg 10 (n=155) RSV RSV combined combined (n=242) ATV ATV 10/20 mg 10/20 (n=155) Total Cholesterol -0.7% * -0.7% -31.9% -31.9% -28.1%* -28.1% -36.8% -32.5% * -32.5% LDL-Cholesterol -0.3% * -0.3% -42.7% -36.6% * -36.6% -48.9% -42.5% * -42.5% HDL-Cholesterol 1.1% * 9.5% 5.1% † 5.1% 10.4% 10.4% 5.8% † 5.8% Non-HDL-Cholesterol Non-HDL-Cholesterol -0.9% * -0.9% -40.6% -35.3% * -35.3% -46.6% -40.8% * -40.8% Triglycerides -2.8% * -2.8% -19.1% -20.9% -20.9% -22.9% -22.9% -25.2% Stalenhoef AFH, et al. Eur Heart J. 2005;26: 2664–2672. SE: standard error of the mean *P < .001 vs. rosuvastatin at same time point † P < .01 vs. rosuvastatin at same time point COMETS Study: COMETS Safety • • Both treatments were well tolerated At Week 12, the overall occurrence of adverse events was At similar in each group similar – 22.2% with rosuvastatin 10 mg / 20 mg (n=158) – 20.7% with atorvastatin 10 mg / 20mg (n=150) – 24.0% with placebo / rosuvastatin 20 mg (n=75) • ALT/CK Changes – Clinically important ALT (> 3x ULN) occurred in 1 patient with Clinically rosuvastatin 10 mg / 20 mg – CK was elevated (> 10x ULN) in 1 patient with atorvastatin 10 mg / 20 mg – CK was elevated (> 10x ULN) with myalgia in 1 patient with CK rosuvastatin 10 mg / 20 mg Stalenhoef AFH, et al. Eur Heart J. 2005;26: 2664–2672. MERCURY I: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy Cholesterol • Objective – To compare the effects of switching to low doses of To rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients cholesterol • Inclusion criteria – A history of CHD or other established atherosclerotic history disease, type 2 diabetes, or a 10-year CHD risk >20% disease, – Fasting LDL-C ≥ 115 mg/dL (≥ 3.0 mmol/L) Fasting 3.0 – TG < 400 mg/dL (< 4.5 mmol/L) TG • Primary end point Primary – Number (%) of patients reaching 1998 European LDL-C goal Number Stender S. Diabetes, Obesity and Metabolism. 2005;7:430–438. at week 16 at Schuster H et al. study. Am Heart J. 2004; 147: 70. Effectiveness of Rosuvastatin Versus Effectiveness Other Statins in Patients With the Metabolic Syndrome‡ Metabolic LDL-C Non-HDL-C Total-C TG HDL-C 20 9.3 10 7.4 7.0 9.6 Change (%) 0 -10 -13.1 -20 -17.3 -26 -30 -40 -50 -20.1 -23.4 -23.9 -20.8 * -29.9 -36.5 -35.1 * -46.7 * -33.6 -24.8 * -33.3 -31.7 * * -42.5 -44.5 -18.5 † -26.9 * -32.3 * -40.8 * * RSV 10 mg (n = 234) ATV 10 mg (n = 222) ATV 20 mg (n = 382) SIM 20 mg (n = 239) PRV 40 mg (n = 224) Analysis performed on intention-to-treat population with last observation carried forward ‡ Post-hoc analysis Stender S. Diabetes, Obesity and Metabolism. 2005;7:430–438. * P < .0001 vs. rosuvastatin from analysis of covariance † P <.0125 vs. rosuvastatin from analysis of covariance RSV: rosuvastatin; ATV: atorvastatin; SIM: simvastatin Patients meeting ATP III goals (%) Percentage of Patients With the Metabolic Percentage Syndrome Meeting ATP III LDL-C Goals While U100 ndergoing Treatment With Select Statins ‡ 80 77 73 62 * 60 51 * 40 34 * 20 n = 234 n = 222 n = 382 n = 239 n = 224 RSV 10 mg 0 ATV 10 mg ATV 20 mg SIM 20 mg PRA 40 mg *P < .0001 vs RSV 10 mg ATP III LDL-C goals are <4.1 mmol/l (160 mg/dL) in patients with no or one risk factor and no coronary heart disease (CHD); <3.4 mmol/l (130 mg/dl) for patients with two or more risk factors and 10-year CHD risk of 20%; <2.6 mmol/l (100 mg/dl) for patients with CHD or CHD equivalents – i.e.other atherosclerotic diseases, diabetes or multiple risk factors and a 10-year CHD risk of >20%. ‡ Post-hoc analysis Goal achievement was analyzed by means of logistic regression RSV: rosuvastatin; ATV: atorvastatin; SIM: simvastatin; PRA: pravastatin Stender S. Diabetes, Obesity and Metabolism. 2005;7:430–438. Hispanic Population Facts and Figures Hispanic • Of the approximate 281 million people living in the Of United States: United – 35.3 million Hispanics or Latinos (largest ethnic minority 35.3 population) population) Hispanic population is growing at a much faster rate Hispanic than the population as a whole (account for than account approximately one-half of the 9.4 million residents added to the US population since Census 2000) added – Hispanic population is expected to increase by nearly Hispanic 67 million between the years 2000 and 2050 (188% increase) • Their share of the nation's population would increase from 12.6 Their U.S. Census Bureau. Population Fact Sheet 2000. Available at: http://factfinder.census.gov/ % to 24.4% o U.S. Census Bureau. Race andtEthnicity Fact Finder. Available at: http://factfinder.census.gov/ Hispanic Population Facts and Figures Hispanic Although • Although Hispanics are the largest ethnic population in the United Sates they are underserved in the health care system care Hispanics • Hispanics are less likely to seek and receive healthcare services receive Center for Disease Control. MMWR Weekly. 2004;40:937-941. Prevalence of Cardiovascular Diseases Among Hispanic-Americans and Non-Hispanic Whites: The Type of Disease Determines LDL-C Goal The Hypertension Dyslipidemia * Mexican American Diabetes † Prior MI White, non-Hispanic † Stroke † 0 * 0-1 Risk Factor: † 2+ Risk Factors: ‡ CHD or Risk Equivalent: 5 10 15 20 25 30 35 40 LDL-C Goal < 160 mg/dL LDL-C Goal < 130 mg/dL LDL-C Goal < 100 mg/dL LDL-C Goal < 70 mg/dL is an option for patients at very high risk Population (%) Adapted from: Trends and Differences in Cardiovascular Health Among Mexican-American and Non-Hispanic White Populations. Available at: http://www.pfizer.com/pfizer/download/health/pubs_facts_cvhealth.pdf. Grundy, S. et al. Arterioscler Thromb Vasc Biol. 2004;24;1329-1330. National Heart, Lung, and Blood Institute. 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): Executive Summary. National Institutes of Health. Bethesda, MD; 2001. NIH Publication 01-3670. MI: myocardial infarction Prevalence and Dyslipidemia Associated Prevalence With the Metabolic Syndrome With Prevalence (% population)* Women Men Non-Hispanic White 22.8 24.8 African-American 25.7 16.4 Mexican-American 35.6 28.3 Other 19.9 20.9 Dyslipidemia associated with the Metabolic Syndrome - Low high density lipoprotein (HDL) cholesterol values – -Increased low density lipoprotein (LDL) values – - Raised apolipoprotein (Apo) B values – - Increased flux of free fatty acids – - Raised TG values * NHANES 1999-2000 data Cossrow N and Falkner B. The Journal of Clinical Endocrinology & Metabolism. 2004;89:2590–2594. Kolovo GD. Postgrad Med J. 2005;81;358-366. Traits Associated with the Metabolic Traits Syndrome by Racial Categories Syndrome 50 White African American Mexican American Other Prevalence (% population) 45 40 35 30 25 20 15 10 5 0 Large Waist High TG Low HDL-C High BP High FPG/DM * * CHD Risk Equivalent LDL-C Goal < 100 mg/dL, < 70 mg/dL is an option for patients at very high risk DM – Diabetes mellitus Meigs J. Am J Manag Care. 2002;8:S283-S292. Trends in Serum Cholesterol Among Trends Adults 20 Years of age and Older by Race/Ethnicity Race/Ethnicity NHANES 1988 - 1994 NHANES 1999 - 2002 250 Mean serum total cholesterol (mg/dL) 206 204 204 200 199 205 202 150 100 50 0 Non-Hispanic White Non-Hispanic Black Heart Disease and Stroke Statistics - 2006 Update. Circulation. 2006;113:e85-e151. Mexican American Screening and Awareness of Dyslipidemia Screening Among Non-Hispanic Whites and MexicanAmong Americans* Hon-Hispanic Whites Mexican American Percent of Patients 70 66 65 60 50 48 42 40 30 20 10 0 Screened for high blood cholesterol level during the preceding 5 years Were aware of high blood cholesterol level † * Individuals 20 years of age and older † % ever told by their health care practitioner that their cholesterol was high, among those with a high blood cholesterol test result, and those who used cholesterol lowering medication. Adapted from: Centers for Disease Control. MMWR Morb Mortal Wkly Rep. 2005;54:117-119. Understanding the Need for Chronic Understanding Treatment with Lipid-lowering Medications Treatment Respondents (%) 50 44 * 40 28 30 27 20 20 10 0 Whites Blacks Englishspeaking Hispanics Non-Englishspeaking Hispanics *P < 0.01 vs Blacks and Hispanics (English and non-English speaking) Kaplan R. Cardiology in Review. 2006;14:1-6. Statin Therapy in a Hispanic-American Population With Hypercholesterolemia: Population STARSHIP Trial - Background STARSHIP • Hispanic individuals: Hispanic – Evidence suggests that they are less frequently screened for Evidence cholesterol levels cholesterol – Should have their lipids managed in the same fashion as nonHispanic white patients (ATP III Panel) – Achievement of lipid-lowering goals is suboptimal – Have been underrepresented in clinical trials of lipid-lowering Have therapies and therefore the safety and efficacy of statin-based lipid-lowering therapy have not been well characterized lipid-lowering Lloret, R. Am J Cardiol. 2006;98:768-773. Statin Therapy in a Hispanic-American Population With Hypercholesterolemia: Population STARSHIP Trial - Endpoints STARSHIP • Primary endpoint – Percentage change from baseline in LDL-C at 6 weeks • Secondary endpoints: • Proportion of patients reaching NCEP ATP III lipid goals (LDL-C goals Proportion overall and by risk category) overall • Patients with baseline TG ≥ 200 mg/dL reaching LDL-C and non-highdensity lipoprotein cholesterol [non-HDL-C] goals • Percentage change from baseline in other lipid measures and lipid ratios Percentage at 6 weeks, including total cholesterol (TC), apolipoprotein (Apo) B, nonat HDL-C, TG, HDL-C, Apo A-I, and LDL-C/HDL-C, TC/HDL-C, non-HDLC/HDL-C, and Apo B/Apo A-I ratios • C-reactive protein (CRP) levels at baseline and after 6 weeks • Safety evaluation included monitoring of adverse events; laboratory Safety evaluation, including clinical chemistry, hematology, and urinalysis; assessment of vital signs; and physical examination assessment Lloret, R. Am J Cardiol. 2006;98:768-773. Overall Changes in Lipid Panel with 10 mg of Rosuvastatin and Atorvastatin After 6 Weeks LDL-C LS Mean Percent change at 6 Weeks 10 HDL-C + 5.5% TG Non-HDL-C + 3.5% 0 -10 -14% -20 -20% -30 -40 -50 -33% -36% -45% Rosuvastatin 10 mg (n=174) Atorvastatin 10 mg (n=161) -41% P < .0001 P < .0001 LS Mean – Least square mean Lloret, R. Am J Cardiol. 2006;98:768-773. Overall Changes in Lipid Panel with 20 mg of Rosuvastatin and Atorvastatin After 6 Weeks LDL-C LS Mean Percent change at 12 Weeks 10 HDL-C TG Non-HDL-C +5.7% +4.3% 0 -10 -20 -18% -22% -30 -40 -39% -42% -50 -60 -50% -45% Rosuvastatin 20 mg (n=167) Atorvastatin 20 mg (n=161) P < 0.01 P < .0001 LS Mean – Least square mean Lloret, R. Am J Cardiol. 2006;98:768-773. Overall Efficacy of Rosuvastatin and Atorvastatin on Goal Attainment 100 Percent achieving LDL-C target 88.0 78.0 80 73.0 60.0 60 40 20 0 RSV 10 mg RSV 20 mg (n = 174) (n = 167) ATV 10 mg ATV 20 mg (n = 161) (n = 161) P=.0002 CRESTOR 10 mg vs atorvastatin 10 mg, Baseline LDL-C in the overall study population ranged from 159 – 165 mg/dL P=.0212 CRESTOR 20 mg vs atorvastatin 20 mg. RSV: rosuvastatin ATV: atorvastatin P = .1726 CRESTOR 10 mg vs atorvastatin 20 mg. Lloret, R. Am J Cardiol. 2006;98:768-773. Percent achieving LDL-C target Efficacy of Rosuvastatin and Efficacy Atorvastatin on Goal Attainment : High Risk Subgroup Risk 100 91 80 74.1 62 60 52 40 20 0 RSV 10 mg RSV 20 mg ATV 10 mg ATV 20 mg (n = 116) (n = 106) (n = 106) (n = 106) High Risk Patients: P=.001 vs atorvastatin 10 mg, NS=CRESTOR 10 mg vs atorvastatin 20 mg. P<.0001 vs atorvastatin 20 mg. Lloret, R. Am J Cardiol. 2006;98:768-773. (LDL-C Goal < 100 mg/dL) Baseline LDL-C in the overall study population ranged from 159 – 165 mg/dL § Retrospective analysis RSV: rosuvastatin ATV: atorvastatin Adverse Events Rosuvastatin Rosuvastatin Atorvastatin 10 mg 10 20 mg 10 mg 20 mg (n = 183) (n = 172) (n = 167) (n = 170) 30% 30% 32% 31% Leading to death 0.0% 0.0% 0.0% 0.0% Leading to study Leading discontinuation discontinuation 2.2% 4.1% 1.8% 1.2% Serious adverse events 1.1% 0.6% 2.4% 1.2% Parameter Any Adverse Event Lloret, R. Am J Cardiol. 2006;98:768-773. Hypercholesterolemia in Hispanic-Americans Summary • Hispanic-Americans make up approximately 12.5 % of the Hispanic-Americans United States population United – Largest minority population • Hypercholesterolemic Hispanics are under-identified and Hypercholesterolemic under-treated compared to non-Hispanic Whites under-treated • Hispanic individuals are: – Less frequently screened for cholesterol levels – Less adequately controlled than other US populations – Underrepresented in clinical trials of lipid-lowering Underrepresented therapies therapies U.S. Census Bureau. Race and Ethnicity Fact Finder. Available at: http://factfinder.census.gov/ . U.S. Census Bureau. Population Fact Sheet 2000. Available at: http://factfinder.census.gov/. Ford ES. Circulation. 2003;107:2185-2199. CDC. Morb Mortal Wkly Rep. 2005;54:117-119. Hypercholesterolemia in Hispanic-Americans Summary (cont.) (cont.) • Since Hispanic individuals have been traditionally Since under-represented in clinical trials employing the use of lipid-lowering therapies, the safety and efficacy of statin therapy in Hispanic patients have not been well characterized characterized • Rosuvastatin therapy (10 and 20 mg/day) enabled Rosuvastatin hypercholesterolemic Hispanic patients to achieve significantly greater reductions in LDL-C and nonsignificantly HDL-C than did milligram equivalents of atorvastatin • Single agent therapy with rosuvastatin as well as Single atorvastatin enabled the majority of patients to reach NCEP ATP III LDL-C goals NCEP Lloret, R. Am J Cardiol. 2006;98:768-773. NCEP III RECOMMENDATIONS Statins •Statins are the first line agents for virtually all patients requiring lipid modification by drugs drugs Single •Single agent therapy with rosuvastatin as well as atorvastatin enable the majority of patients to reach NCEP ATP III LDL-C goals patients Nicotinic •Nicotinic acid, fibrates, omega-3 fatty acids or ezetimibe may be considered as adjunctive therapies, not alternatives for high-risk patients with residual high TG or low HDL-C patients Randomized Evidence For Lipid Modifying Drugs On Clinical Outcomes Drugs • • • Statins Nicotinic Acid ~ 2800 Fibrates – Gemfibrozil – Fenofibrate • • ~ 90000 ~ ~ 2500 10000 (p=ns) Omega-3-FA ~ 11000 Ezetimibe 0 French Fries French 20 years ago 210 calories 2.4 ounces Today 610 calories How manycalories are in6.9 ounces these fries? Calorie difference: 400 Calories How to burn* 400 calories: Walk 2 hour 20 minutes *Based on 130-pound person. Darwinism and Risk of Cardiovascular Disease of Walking the Dog Walking Established Risk Factors for CHD Established Blood cholesterol 10% ↓ = 20%-30% ↓ in CHD 10% High blood pressure 5-6 mm Hg ↓ = 42% ↓ in Stroke 5-6 = 16% ↓ in CHD Cigarette smoking Cessation = 50%-70% ↓ in CHD Cessation Body weight BMI<25 vs BMI>27 = 35%-55% ↓ in CHD Physical activity 20-minute brisk walk daily = 35%-55% ↓ in CHD 20-minute CHIEF AVOIDABLE CAUSES OF PREMATURE DEATH IN THE US PREMATURE • • • • • • CIGARETTES OBESITY PHYSICAL INACTIVITY LIPIDS BLOOD PRESSURE HEAVY ALCOHOL CONSUMPTION “We must all hang together, or assuredly We we shall all hang separately.” we – Benjamin Franklin Benjamin July 4, 1776 ...
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