6Major Statin Trials % with CAD event LDL-C (mg/dL) 25 Secondary 20 PROVE IT254SSecondaryHPS20Mixed15PROSPER% with CAD eventPrimaryLIPIDCARE10WOSCOPSTNTIn primary prevention trials, reduction of LDL-C levels with statins was associated with a reduction in the risk of CAD events, both in patients with elevated (WOSCOPS) and average (AFCAPS/TexCAPS) LDL-C serum concentrations.Similarly, in secondary prevention trials, reduction of LDL-C levels with statins was associated with a reduction in the risk of CAD events, both in patients with elevated (4S) and average (CARE, LIPID) LDL-C serum concentrations.5ASCOT-LLAJUPITERAFCAPS507090110130150170190210LDL-C (mg/dL)Illingworth DR. Management of hypercholesterolemia. Med Clin North Am. 2000;84:23-42.
8Intravascular Ultrasound Images at Baseline and Follow-up REVERSAL TrialIntravascular Ultrasound Images at Baseline and Follow-upNissen, S. E. et al. JAMA 2004;291:
9Limitations to Pharmacologic Lipid Management Cost of treatmentNot an issue if generic drug will control LDL-CTreatment cost ~ $1000 per year if non-generic agent neededNot all patients tolerant of statinsMyalgia most common complaint (5-15%)Alternative drugs (intestinal agents, niacin, fibrates) have limited effect on LDL-C, limited outcome dataBenefits of add-on drug therapy not established
10International Comparisons 2002 AHA Heart and Stroke Statistical Update(Men ages 35-74)International rates not due to differences in statin therapy rates!
11Diets and CAD: What’s the Evidence? Dietary therapy can be an alternative to pharmacologic management of lipids in primary preventionImportant adjunctive therapy in secondary preventionWhat is the best diet for CHD prevention?
13Mortality from Coronary Heart Disease Men 35-64 Years (1969-1994) 800Cardiac death rates have dropped by 75%!700600Now 80%500Per 100,000North Karelia400300All Finland200100Puska P: Cardiovasc Risk factors 6:203-10, 1996CP
14Trends in Women’s Lifestyles 1980-82 versus 1992-94 31% decline in CHD incidence across all ages41% decrease in smoking (27% 16%)Diet changes31% decrease in trans fatty acid intake69% increase in P/S ratio90% increase in cereal fiber180% increase in -3 fatty acids12% increase in folateNurses’ Health Study -- Hu et al: NEJM 2000;343:
15Trends in Women’s Lifestyles 1980-82 versus 1992-94 38% increase in overweight (BMI>25)average BMI 24.5 26.1 kg/m222% increase in glycemic load
16Regional Diets with Low CHD Rates Seventh Day AdventistJapaneseRural ChineseEskimoMediterranean
18Adherence to Mediterranean Diet and Survival in a Greek Population Prospective, population-based investigation of CHD mortality versus diet22,043 healthy adults in Greece44-month follow-upDiet assessed by 10-point scale (0-9)vegetables, legumes, fruits and nuts, cereals, fish, alcohol, monounsaturated/saturated fat ratio (+)meat, poultry, dairy products (-)Trichopoulou A et al, NEJM 2003:348:
19Results Two single nutrients predicted CHD death Fruits and nuts: +200 g/day = 18% reductionMonounsaturated/saturated fat ratio: = 14% reduction2-point increase in Mediterranean diet score25% reduction in total mortality33% reduction in CHD mortality24% reduction in cancer mortalityAdjusted for age, sex, WHR, energy expenditure, smoking, BMI, potato and egg consumption, and total caloric intake
20Epidemiologic Studies Inherently flawedProblems with ascertainment of both independent (diets) and dependent (mortality, heart attacks, etc.) variablesNot all non-dietary variables can be measured (and none controlled)Assumes constancy of exposure to dietary factors
21Diet-Heart Studies with Outcomes Location N Year f/uEngland (Rose) yMiddlesex yOslo yLondon ySydney yDART yMoradabad yLHT (invite) yLeon yInterventioncontrol v corn oil v olive oilcontrol v low fatcontrol v low fat + PUFcontrol v soya-bean oillow fat v fish v fiberlow fat v fruit/veg+fish+fibercontrol v ultra-low fatcontrol v Mediterranean
25Lifestyle Heart Trial 1-Year Results Not powered (or randomized) for clinical events
26Lyon Heart Study 423 patients randomized post-MI 1988-92 Mediterranean diet vs “prudent diet” (Step 1) prescribed by patients’ physiciansPlanned 5-year follow-upStudy terminated early (4 years) due to favorable interim analysis -- final report on 423 patientsde Lorgeril et al, Circ 1999;99:
27The Traditional Healthy Mediterranean Diet Pyramid MeatSweetsEggsPoultryFishCheese & yogurtOlive oilFruitsBread, pasta, rice, couscous, polenta, other whole grains & potatoesDaily physical activityDaily beverage recommendations6 glasses of waterWine in moderationVegetablesBeans, legumes & nutsMonthlyWeeklyDaily2000 Oldways Preservation & Exchange TrustCP
29Lyon Heart Study Results consistent with DART and Moradabad trials p<.0002p<.0001p<.0001Results consistent with DART and Moradabad trials
30Search for the Perfect CHD Prevention Diet The Lifestyle Heart Trial achieved marked LDL-C lowering, but adversely affected HDL-CThe Leon Heart Study lowered CHD risk without affecting lipid levelsCan we design a diet that lowers LDL-C without lowering HDL-C while providing the heart protective nutrients?
31Therapeutic Lifestyle Changes in LDL-Lowering Therapy Major FeaturesTLC Diet (Step 2+)Reduced intake of cholesterol-raising nutrients (same as previous Step II Diet)Saturated fats <7% of total caloriesDietary cholesterol <200 mg per dayLDL-lowering therapeutic optionsPlant stanols/sterols (2 g per day)Viscous (soluble) fiber (10–25 g per day)Weight reductionIncreased physical activityNCEP
32Other Features of TLC Diet Nutrient Recommended IntakePolyunsaturated fat Up to 10% of total caloriesMonounsaturated fat Up to 20% of total caloriesTotal fat 25–35% of total caloriesCarbohydrate 50–60% of total caloriesFiber 20–30 grams per dayProtein Approximately 15% of total caloriesTotal calories (energy) Balance energy intake and expenditure to maintain desirable body weight/ prevent weight gain
36Summary: Best CHD Prevention Diet Low in saturated fat and cholesterolHigh in monounsaturated fatFish 2+ servings per weekOr omega-3 fatty acids supplementFresh fruits and vegetables 7+ servings/dayWhole grains in place of refined flour and sugar
37Best CHD Prevention Diet Nuts 14+ grams/1000 kcalAdded soy protein, soluble fiber, phytosterolsLow glycemic index, especially if overweightCalorie control should be automaticLow caloric density CHO’sSatiety from monounsaturated fats, proteinsHighly palatableVariety of foods and seasonings
38strategy to reduce cardiovascular disease by more than 75% BMJ 2004;329: (18 December), doi: /bmjThe limits of medicineThe Polymeal: a more natural, safer, and probably tastier (than the Polypill)strategy to reduce cardiovascular disease by more than 75%Oscar H Franco, scientific researcher1, Luc Bonneux, senior researcher2, Chris de Laet, senior researcher1, Anna Peeters, senior researcher3, Ewout W Steyerberg, associate professor1, Johan P Mackenbach, professor11 Department of Public Health, Erasmus MC University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands, 2 Belgian Health Care Knowledge Centre (KCE), Wetstraat 155, B-1040, Brussels, Belgium, 3 Department of Epidemiology and Preventive Medicine, Monash University Central and Eastern Clinical School, Melbourne, Australia
39IngredientsPercentage reduction (95% CI) in risk of CVDSourceWine (150 ml/day)32 (23 to 41)Di Castelnuovo et al (MA)6Fish (114 g four times/week)14 (8 to 19)Whelton et al (MA)7Dark chocolate (100 g/day)21 (14 to 27)Taubert et al (RCT)8Fruit and vegetables (400 g/day)John et al (RCT)10Garlic (2.7 g/day)25 (21 to 27)Ackermann et al (MA)11Almonds (68 g/day)12.5 (10.5 to 13.5)Jenkins et al (RCT),15 Sabate et al (RCT)16Combined effect76 (63 to 84)
40Other Aspects of Polymeal Men at age 50 would live an average of 6.6 years longerWomen at age 50, 4.8 years longerCost of polymeal estimated at $28.10/weekAddition of other components such as oat bran or olive oil would only enhance effectNo obvious contraindications to combining polymeal with polypill (or any subset of components)
42Weight Loss Controversy Americans have substituted refined CHO’s for fats over the past 20 yearsLinked to obesityLow CHO versus low fat for weight lossAtkins versus OrnishMuch speculation, many popular booksPublished data only in past 4-5 yearsDoes losing weight necessarily mean lowering CHD risk?
43Effect of Varying Fat, Protein, and CHO Content on Weight Loss 811 overweight adults randomized to 3 weight loss diets for 2 yearsVarying content: fat protein CHODiet % 15% 65%Diet % 25% 55%Diet % 15% 45%Diet % 25% 35%750 kcal per day caloric deficitSacks FM et al. NEJM 2009;360: