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  • 5.10
  • The recommendation to treat overweight and obesity is based not only on the evidence that shows overweight is associated with increased morbidity and mortality, but also on RCT evidence that weight loss reduces risk factors for disease. Thus, weight loss may help control diseases worsened by overweight and obesity and may also decrease the likelihood of developing these diseases. Some benefits associated with weight loss include the following: Decreased cardiovascular risk. Decreased glucose and insulin levels. Decreased blood pressure. Decreased LDL-cholesterol and triglycerides and increased HDL-cholesterol. Decreased severity of sleep apnea. Reduced symptoms of degenerative joint disease. Improved gynecological conditions.
  • When physicians encounter patients in the clinical setting, the opportunity exists for: Identifying overweight and obesity and accompanying risk factors. Initiating treatment for both the weight and the risk factors, as well as chronic diseases such as CVD and type 2 diabetes. Consider the patient’s weight, waist circumference, and the presence of disease conditions or risk factors when assessing a patient for treatment of overweight and obesity. The strategy for the evaluation and treatment of overweight patients is presented in these slides of the Treatment Algorithm. This algorithm applies only to the assessment for overweight and obesity and subsequent decisions based on that assessment. It does not reflect any initial overall assessment for cardiovascular risk factors or diseases that are indicated. In overweight patients, control of cardiovascular risk factors deserves the same emphasis as weight loss therapy. Reduction of risk factors will reduce the risk for CVD whether or not efforts at weight loss are successful.
  • To achieve the greatest likelihood of success from weight loss therapy, therapy should include a combination of: Low-calorie, low-fat diets Increased physical activity Behavior modification Clinical trials have demonstrated that combining low-calorie diets, increased physical activity, and behavior therapy provides better outcomes for long-term weight reduction than programs that use only one or two of the modalities.
  • As recommended by JNC 7, hypertension treatment should start with lifestyle modifications. If the patient is not at goal BP of <140/90 mm Hg (<130/80 mm Hg for those with diabetes or chronic kidney disease), pharmacologic therapy should be initiated. 32 Initial drug choices for patients without compelling indications should be a thiazide diuretic for most patients with stage 1 hypertension. Typically, combination therapy with 2 drugs is required for stage 2 hypertension. When use of a single drug fails to achieve the BP goal, addition of a second drug from a different class should be initiated. A 2-drug combination usually consists of a thiazide-type diuretic plus an ACEI, an ARB, a  -blocker, or a CCB. Specific antihypertensives are designated for compelling indications (eg, HF, post-MI, high coronary artery disease [CAD] risk, diabetes, etc). 30 If a patient is still not at goal BP following the treatment algorithm, optimize the patient’s dosages or add additional drugs until goal BP is achieved. Also consider consulting with a hypertension specialist. 30 30. Chobanian AV, Bakris GL, Black HR, et al, and the National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA . 2003;289:2560-2572.
  • Data from the Framingham Heart Study show the continuous relationship between risk of developing CVD over 8 years and levels of cholesterol. 9 Other assumptions for this model are that the patient was a 40-year-old man, who was ECG left ventricular hypertrophy (LVH) negative, and with no glucose intolerance, and who was not a current smoker. As illustrated on this slide, the relationship between level of total cholesterol (TC) and CVD risk is graded and continuous. Risk is not confined to the upper centiles. 9 9. Kannel WB. Importance of hypertension as a major risk factor in cardiovascular disease. In: Genest J, Koiw E, Kuchel O, eds. Hypertension. Physiopathology and Treatment. New York, NY: McGraw-Hill; 1977:888-910.
  • Slide 3. Total cholesterol distribution: CHD vs non-CHD population In the Framingham Heart Study, as many as one third of all coronary heart disease (CHD) events occurred in individuals with total cholesterol <200 mg/dL. Considering that the average U.S. cholesterol level is approximately 210 to 220 mg/dL, almost half of all heart attack events and all stroke events that will occur in the United States next year will in fact occur among individuals with below-average lipid levels. For this reason, our research group has sought in our large-scale prospective epidemiologic studies to understand better other markers associated with cardiovascular risk. Reference: Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 1996;124(Suppl):S1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8831910&dopt=Abstract Keywords: cholesterol distribution, Framingham Heart Study Slide type: graph
  • Slide 5 Effects of Increasing TC Levels on the Risk for CHD in the Presence of Other Risk Factors. The Framingham Heart Study showed the effects of increasing total cholesterol levels on the risk for CHD in the presence of other risk factors in men aged 50 years. As shown, low HDL-C poses an even greater risk than smoking, hyperglycemia, and hypertension.
  • Speaker’s Notes/Talking Points: Low high-density lipoprotein cholesterol (HDL-C) levels (< 40 mg/dL) are associated with an increased risk of coronary heart disease (CHD) even if the total cholesterol (Total-C) level is < 200 mg/dL. This slide shows the CHD incidence over 14 years among Framingham Study subjects who were aged 48–83 years at baseline. 1 Among those with HDL-C levels < 40 mg/dL and Total-C < 200 mg/dL, 11.24% experienced a CHD event. This incidence was virtually the same as that (11.91%) for subjects with HDL-C levels between 40–49 mg/dL and Total-C  260 mg/dL. References 1. Castelli WP, Garrison RJ, Wilson PW, et al. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA. 1986;256:2835–2838.
  • The British Heart Protection Study, presented in 2001 at the American Heart Association meeting, followed approximately 20,000 patients over a period of 5 years. The initial entry criteria was age between 40 and 80 years, a total cholesterol of at least 135 mg/dL, and no clear indications or contraindications for statins or vitamins by the patient’s physicians. 5.36 Heart Protection Study. Presented at American Heart Association 2001 Scientific Session, Anaheim, CA on 11/13/01.
  • Allocation to simvastatin also produced an extreme 38% proportional reduction in incidence of first nonfatal myocardial infarction following randomization (357 [3.5%] simvastatin vs 574 [5.6%] placebo; p<0.0001). Combining this with the effect on coronary death rate, there was a 27% proportional reduction in the incidence rate of ‘major coronary events’ (MCE): (898 [8.7%] vs 1212 [11.8%]; p<0.0001). Simvastatin treatment also resulted in a highly significant 24% proportional reduction in the incidence rate of first revascularization procedure following randomization (939 [9.1%] simvastatin vs 1205 [11.7%] placebo; p<0.0001). A 30% proportional reduction in the incidence rate of coronary revascularization occurred (513 [5.0%] vs 725 [7.1%]; p<0.0001), and there was also a significant 16% proportional reduction in the incidence rate of noncoronary revascularization (450 [4.4%] vs 532 [5.2%]; p=0.006). Major vascular events of any kind were reported in significantly fewer patients allocated to simvastatin compared to placebo (2033 [19.8%] vs 2585 [25.2%]; p<0.0001).
  • During the open-label period, LDL-C was reduced by 35% in the overall patient population, from 152 mg/dL (3.9 mmol/L) to 98 mg/dL (2.6 mmol/L). 1 Following randomization, mean LDL-C in the atorvastatin 10-mg group was maintained at approximately baseline level for the duration of the treatment period, with an average of 101 mg/dL (2.6 mmol/L) across the 5 years of follow-up. 1 After 12 weeks of treatment, LDL-C was further reduced to a mean level of 77 mg/dL (2.0 mmol/L; P <.001) among patients receiving atorvastatin 80 mg. 1 The LDL-C level in the 80-mg group remained relatively stable over the course of the study. 1 Reference 1. LaRosa JC, Grundy SM, Waters DD, et al, for the Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med . 2005;352:1425-1435.
  • Over the course of the study, there was a highly significant reduction in the composite efficacy outcome of major cardiovascular events in the atorvastatin 80-mg group compared with the atorvastatin 10-mg group. 1 The Kaplan-Meier analysis showed a hazard ratio of 0.78 (95% CI 0.69, 0.89; P <.001). 1 This represented a 22% reduction in relative risk in the atorvastatin 80-mg group relative to the atorvastatin 10-mg group, over and above the low absolute event rate of 10.9% recorded in the atorvastatin 10-mg group. 1 There was no statistical interaction for age or sex in the primary outcome measure. 1 Reference 1. LaRosa JC, Grundy SM, Waters DD, et al, for the Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med . 2005;352:1425-1435.
  • Summary (I) In patients at high or moderately risk, therapeutic lifestyle change is an integral part of risk reduction. If an LDL-C –lowering drug is used, the intensity of therapy should achieve an additional LDL-C reduction of at least 30–40% beyond diet.
  • At their starting dosages, all of the currently available statins reduce levels of LDL cholesterol and triglycerides, and increase levels of HDL cholesterol. Rosuvastatin is the most potent at LDL lowering. Reference Product Data Sheets
  • Lipid-modifying therapies include HMG CoA reductase inhibitors (statins), fibrates, bile acid sequestrants (resins), nicotinic acid and its derivatives, and probucol. Statins are highly effective in lowering LDL-cholesterol and have a good tolerability profile. 1-3 Data presented in this slide does not include rosuvastatin. Bile acid sequestrants are potent cholesterol-modifying agents. Adverse events such as gastrointestinal bloating, nausea and constipation limit compliance to the bile acid sequestrants. 1,2 Nicotinic acid , a B-complex vitamin, is effective at reducing both LDL cholesterol and triglyceride concentrations, and increasing HDL cholesterol levels. To be effective, it must be given in pharmacologic doses. The value of nicotinic acid has been limited by the incidence of adverse events, which include flushing, skin problems, gastrointestinal distress, liver toxicity, hyperglycaemia and hyperuricemia. 1,2 Fibrates are effective triglyceride-lowering and HDL-raising drugs. However, in the majority of patients they are only moderately successful in reducing LDL-cholesterol. 1,2 Probucol is not available in most countries. It has only a modest LDL-cholesterol-lowering effect, and there is no evidence that it reduces CHD risk and there are limited long-term tolerability data. 1,2 Ezetimibe is the first of a novel class of selective cholesterol-absorption inhibitors. Ezetimibe may be useful in patients who are intolerant to other lipid-modifying therapies, and in combination with a statin in patients who are intolerant to large doses of statins or need further reductions in LDL cholesterol despite maximum doses of a statin. 4 References 1. Yeshurun D, Gotto AM. Southern Med J 1995; 88(4) :379–391. 2. National Cholesterol Education Program. Circulation 1994; 98(3) :1333–1445. 3. Knopp RH. N Engl J Med 1999; 341 :498–511. 4. Gupta EK, Ito MK. Heart Dis 2002; 4 :399–409.
  • Speaker’s Notes/Talking Points: The treatment of cardiovascular risk factors in patients with diabetes is controversial, with some investigators suggesting that such patients should be treated as though they had established coronary heart disease (CHD). 1 To determine whether diabetic patients who have not had myocardial infarctions (MIs) should be treated as aggressively for cardiovascular risk factors as diabetic patients who have had MIs, Haffner and colleagues compared the 7-year incidence of MI (both fatal and nonfatal) among 1,378 nondiabetic subjects with the MI incidence among 1,059 subjects with non-insulin-dependent diabetes mellitus (NIDDM) in a Finnish population-based study. 2 The probability of death from CHD was estimated among diabetic and nondiabetic subjects, with and without prior MI. As this slide shows, the probability of death from CHD was highest among diabetic subjects with prior MI and was lowest among nondiabetic subjects without prior MI. Diabetic subjects without prior MI and nondiabetic subjects with prior MI had intermediate survival rates as well as similar outcomes. These findings suggest that cardiovascular risk factors should be treated in diabetic patients as aggressively as in nondiabetic patients with prior MI. References 1. Haffner SM. The Scandinavian Simvastatin Survival Study (4S) subgroup analysis of diabetic subjects: implications for the prevention of coronary heart disease. Diabetes Care. 1997;20:469–471. 2. Haffner SM, Lehto S, Ronnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234.
  • Insulin resistance is a precursor to a variety of metabolic abnormalities, including systemic inflammation, visceral obesity, and type 2 diabetes. Insulin resistance is also a risk factor for cardiovascular abnormalities, including hypertension, dyslipidemia (increased triglycerides and LDL and decreased HDL), disordered fibrinolysis, and endothelial dysfunction. All of these aberrations contribute to the atherosclerotic process. Consensus Development Conference of the American Diabetes Association. Diabetes Care. 1998;21:310-314. Pradhan AD et al. JAMA. 2001;286:327-334.
  • Differences between study groups in occurrence of major vascular events were nonsignificant. Major coronary events included nonfatal myocardial infarction and coronary death, and occurred in 1063 (10.4%) vitamin-allocated subjects and 1047 (10.2%) placebo-allocated subjects. Strokes (nonfatal or fatal) occurred in 511 (5.0%) vitamin-allocated subjects and 518 (5.0%) placebo-allocated subjects. Revascularizations (coronary and noncoronary) were reported in 1058 (10.3%) individuals in the vitamin group and 1086 (10.6%) individuals in the placebo group. The number of participants who experienced major vascular events of any type was nearly identical in the vitamin group (2306 [22.5%]) and the placebo group (2312 [22.5%]). Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet . 2002;360:23 –33 .
  • Slide 11. Heart and Estrogen/Progestin Replacement Study (HERS): secondary prevention of CHD in women HERS examined the observational association between estrogen replacement and CHD risk reduction in a randomized prospective trial of estrogen plus MPA at fixed dosages in women with CHD.   Reference: Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E, for the Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998;280:605-613.
  • Slide 13. HERS results: summary On the basis of the HERS results, the investigators concluded that a woman with CHD who is already on hormone-replacement therapy should not discontinue therapy, because hormone treatment reduced CHD risk at later time points during the study. However, with the lack of overall CHD benefit combined with a trend toward increased CHD risk, the authors did not recommend initiating hormone-replacement therapy as secondary prevention in a woman not currently on therapy.   Reference: Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E, for the Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998;280:605-613.
  • Women and Heart Disease powerpoint_logo3

    1. 1. Heart Disease in Women: New Concepts in Prevention and Management of Dyslipidemia and Other Risk Factors <ul><li>Nathan D. Wong, PhD, FACC </li></ul><ul><li>Professor and Director </li></ul><ul><li>Heart Disease Prevention Program </li></ul><ul><li>Division of Cardiology </li></ul><ul><li>University of California, Irvine </li></ul>
    2. 2. Cardiovascular Disease in Women <ul><li>38.2 million women (34%) are living with cardiovascular disease and a much larger population is at risk. </li></ul><ul><li>Heart disease and stroke are the no. 1 and no. 3 killers of women over age 25 </li></ul><ul><li>1 in 30 die of breast cancer, but 1 in 2.5 die of cardiovascular disease or stroke. </li></ul><ul><li>66,000 more women than men die per year of cardiovascular disease; represents 54% of deaths in women compared to 46% in men. </li></ul>AHA Heart Disease and Stroke Statistics 2004 Update, and Mosca et al., Circulation 2007; 115: 1481-1501.
    3. 3. Cardiovascular disease mortality trends for males and females ( United States: 1979-2004). Source: NCHS and NHLBI. 0
    4. 4. Note: Hospital discharges include people discharged alive, dead, and status unknown. Hospital discharges for coronary heart disease by sex (United States: 1970-2004). Source: NHDS, /NCHS and NHLBI.
    5. 5. Note: Hospital discharges include people discharged alive, dead and status unknown.. Hospital discharges for heart failure by sex (United States: 1979-2004). Source: NHDS, NCHS and NHLBI.
    6. 6. Source: FHS, 1980-2003. NHLBI. Incidence of cardiovascular disease* by age and sex * Includes CHD, HF, stroke or IC.
    7. 7. Deaths in Thousands A Total CVD B Cancer C Accidents D Chronic Lower Respiratory Diseases E Diabetes Mellitus F Alzheimer’s Disease Leading causes of death for all males and females ( United States: 2004). Source: NCHS and NHLBI.
    8. 8. Estimated 10-Year Stroke Risk in 55-Year-Old Adults According to Levels of Various Risk Factors – Framingham Heart Study p16 A B C D E F Systolic BP * 95-105 130-148 130-148 130-148 130-148 130-148 Diabetes No No Yes Yes Yes Yes Cigarettes No No No Yes Yes Yes Prior Atrial Fibrillation No No No No Yes Yes Prior CVD No No No No No Yes * Blood pressures are in millimeters of mercury (mm Hg). Source: Wolf, PA, et al. Stroke. 1991;22:312-318.
    9. 9. Say ALOHA to Heart Disease in Women <ul><li>A – Assess your risk: high, intermediate, or low? </li></ul><ul><li>L – Lifestyle recommendations are first priority </li></ul><ul><li>O – Other interventions prioritized according to expert panel rating scale </li></ul><ul><li>H – Highest priority for therapy is for women at highest risk </li></ul><ul><li>A – Avoid medical therapies called Class III where evidence is lacking </li></ul>Mosca L. Circulation 2004
    10. 10. A - Assessment of CHD Risk Classification of CVD Risk in Women (Mosca et al., Circ 2007) <ul><li>High Risk: </li></ul><ul><ul><li>Established coronary heart disease </li></ul></ul><ul><ul><li>Cerebrovascular disease </li></ul></ul><ul><ul><li>Peripheral arterial disease </li></ul></ul><ul><ul><li>Abdominal aortic aneurysm </li></ul></ul><ul><ul><li>End-stage or chronic renal disease </li></ul></ul><ul><ul><li>Diabetes mellitus </li></ul></ul><ul><ul><li>10-year Framingham global risk >20% </li></ul></ul>
    11. 11. Classification of CVD Risk in Women (Mosca et al., Circ 2007) <ul><li>At Risk: </li></ul><ul><ul><li>Evidence of subclinical vascular disease (e.g., coronary calcium) </li></ul></ul><ul><ul><li>Metabolic Syndrome </li></ul></ul><ul><ul><li>Poor exercise capacity on treadmill and/or abnormal heart rate recovery </li></ul></ul><ul><ul><li>>=1 major risk factor for CVD including: </li></ul></ul><ul><ul><ul><li>Cigarette smoking </li></ul></ul></ul><ul><ul><ul><li>Poor diet </li></ul></ul></ul><ul><ul><ul><li>Physical inactivity </li></ul></ul></ul><ul><ul><ul><li>Obesity (esp central obesity) </li></ul></ul></ul><ul><ul><ul><li>Family history of premature CVD (<55 male or <65 female relative) </li></ul></ul></ul><ul><ul><ul><li>Hypertension </li></ul></ul></ul><ul><ul><ul><li>Dyslipidemia </li></ul></ul></ul><ul><li>Optimal risk : Framingham global risk <10% and a healthy lifestyle with no risk factors </li></ul>
    12. 12. <ul><li>For persons without known CHD, other forms of atherosclerotic disease, or diabetes: </li></ul><ul><li>Count the number of risk factors. </li></ul><ul><li>Use Framingham scoring if  2 risk factors* to determine the absolute 10-year CHD risk. </li></ul><ul><li>Determine risk status: high (>20% 10-year risk or CHD risk equivalents), intermediate (10-20% 10-year risk), or low (<10% risk) </li></ul>*For persons with 0–1 risk factor, Framingham calculations are not necessary. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 2001;285:2486-2497. © 2001, Professional Postgraduate Services ® www.lipidhealth.org
    13. 13. Assessing CHD Risk in Women Point Total 10-Year Risk Point Total 10-Year Risk <9 <1% 20 11% 9 1% 21 14% 10 1% 22 17% 11 1% 23 22% 12 1% 24 27% 13 2%  25  30% 14 2% 15 3% 16 4% 17 5% 18 6% 19 8% Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 2001;285:2486-2497. TC Points at Points at Points at Points at Points at (mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 0 0 0 0 0 160-199 4 3 2 1 1 200-239 8 6 4 2 1 240-279 11 8 5 3 2  280 13 10 7 4 2 Step 7: CHD Risk Step 2: Total Cholesterol ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org Step 1: Age Years Points 20-34 -7 35-39 -3 40-44 0 45-49 3 50-54 6 55-59 8 60-64 10 65-69 12 70-74 14 75-79 16 HDL-C (mg/dL) Points  60 -1 50-59 0 40-49 1 <40 2 Step 3: HDL-Cholesterol Systolic BP Points Points (mm Hg) if Untreated if Treated <120 0 0 120-129 1 3 130-139 2 4 140-159 3 5  160 4 6 Step 4: Systolic Blood Pressure Step 5: Smoking Status Nonsmoker 0 0 0 0 0 Smoker 9 7 4 2 1 Age Total cholesterol HDL-cholesterol Systolic blood pressure Smoking status Point total Step 6: Adding Up the Points
    14. 14. Recommendations for Noninvasive Screening <ul><li>AHA Prevention V (Greenland et al., Circ. 2000) indicated persons at intermediate risk may be suitable for screening by noninvasive tests, including ABI and carotid US for those over age 50 years, and coronary calcium screening. </li></ul><ul><li>ATP III has suggested CAC scores above 75 th percentile indications for more aggressive treatment (e.g., as CHD risk equivalent). </li></ul>
    15. 16. Cardiovascular Health Study: Combined intimal-medial thickness predicts total MI and stroke Cardiovascular Health Study (CHS) (aged 65+): MI or stroke rate 25% over 7 years in those at highest quintile of combined IMT (O’Leary et al. 1999)
    16. 17. Significant Coronary Artery Calcium (Score >400)
    17. 18. Risk of Total Mortality by Calcium Category in 10,377 Asymptomatic Individuals Shaw LJ et al., Radiology 2003; 228: 826-33
    18. 19. L – Lifestyle Change: First Line of Defense Against Heart Disease <ul><li>The AHA expert panel rated the following as Class I recommendations: </li></ul><ul><ul><li>Stop cigarette smoking and avoid secondhand tobacco smoke </li></ul></ul><ul><ul><li>Get at least 30 minutes of physical activity most or preferably all days (60-90 minutes for those needing to lose or sustain weight) </li></ul></ul><ul><ul><li>Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event </li></ul></ul><ul><ul><li>Eat a heart-healthy diet (consistent with NCEP/ATP III TLC) </li></ul></ul><ul><ul><li>Maintain healthy weight by balancing caloric intake with caloric expenditure to achieve BMI between 18.5-24.9 kg/m 2 </li></ul></ul>Mosca et al. Circulation 2004 and 2007
    19. 20. Other Recommendations <ul><li>The following are Class II recommendations: </li></ul><ul><ul><li>Omega-3 fatty acids (850-1000 mg EPA and DHA per day) may be considered in women with CHD, higher doses in those with high TG </li></ul></ul><ul><ul><li>Consider screening women with CHD for depression and refer/treat where indicated </li></ul></ul>
    20. 22. ATP III: Nutritional Components of the TLC Diet Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 2001;285:2486-2497. *Trans fatty acids also raise LDL-C and should be kept at a low intake. Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight. © 2001, Professional Postgraduate Services ® www.lipidhealth.org <200 mg/d Cholesterol ~15% of total calories Protein 20–30 g/d Fiber 50%–60% of total calories Carbohydrate (esp. complex carbs) 25%–35% of total calories Total fat Up to 20% of total calories Monounsaturated fat Up to 10% of total calories Polyunsaturated fat <7% of total calories Saturated fat* Recommended Intake Nutrient
    21. 23. Possible Benefits From Other Therapies Therapy Result <ul><li>Soluble fiber in diet (2 – 8 g/d) (oat bran, fruit, and vegetables) </li></ul><ul><li>Soy protein (20 – 30 g/d) </li></ul><ul><li>Stanol esters (1.5 – 4 g/d) (inhibit cholesterol absorption) </li></ul><ul><li>Fish oils (3 – 9 g/d) </li></ul><ul><li>(n-3 fatty acids) </li></ul> LDL-C 1% to 10%  LDL-C 5% to 7%  LDL-C 10% to 15%  Triglycerides 25% to 35% Jones PJ. Curr Atheroscler Rep. 1999;1:230-235. Lichtenstein AH. Curr Atheroscler Rep. 1999;1:210-214. Rambjor GS et al. Lipids. 1996;31:S45-S49. Ripsin CM et al. JAMA. 1992;267:3317-3325.
    22. 24. Nuts, Soy, Phytosterols, Garlic <ul><li>Nurses’ Health Study: five 1oz servings of nuts per week associated with 40% lower risk of CHD events; 2-4 servings/wk 25% lower risk </li></ul><ul><li>Metaanalysis of 38 trials of soy protein showed 47g intake lowered total, LDL-C, and trigs 9%, 13%, and 11%, respectively; no effect on HDL-C. </li></ul><ul><li>Phytosterol-supplemented foods (e.g., stanol ester margarine) lowers LDL-C avg. 10% </li></ul><ul><li>Meta-analysis of garlic studies showed 9% total cholesterol reduction from 1/2-1 clove consumed daily for 6 months. </li></ul>
    23. 26. BMI and Relative Risk of CHD Over 14 Years: Nurse’s Health Study <ul><li>Relative risk of CHD increases for BMI > 23, diabetes risk increases for BMI > 22. </li></ul><ul><li>Risk also significantly increases for weight gain after age 18 years of 5 kg or more. </li></ul>
    24. 27. Health Benefits of Weight Loss <ul><ul><li>Decreased cardiovascular risk </li></ul></ul><ul><ul><li>Decreased glucose and insulin levels </li></ul></ul><ul><ul><li>Decreased blood pressure </li></ul></ul><ul><ul><li>Decreased LDL and triglycerides, increased HDL </li></ul></ul><ul><ul><li>Decrease in severity of sleep apnea </li></ul></ul><ul><ul><li>Reduced symptoms of degenerative joint disease </li></ul></ul><ul><ul><li>Improved gynecological conditions </li></ul></ul>
    25. 28. National Obesity Education Initiative Treatment Algorithm Patient Encounter Hx of 25 BMI?  • Measure weight, height, and waist circumference • Calculate BMI Examination Brief reinforcement/ educate on weight management Periodic weight check Advise to maintain weight/address other risk factors Clinician and patient devise goals and treatment strategy for weight loss and risk factor control Assess reasons for failure to lose weight Maintenance counseling: Dietary therapy Behavior therapy Physical activity : Treatment Assess risk factors No Yes 1 2 14 15 13 12 11 10 16 3 4 6 5 7 8 9 Yes No Yes No Hx BMI 25?   No Yes Yes No Does patient want to lose weight? Yes No Progress being made/goal achieved? BMI 25 OR   waist circumference > 88 cm (F) > 102 cm (M) BMI   30 OR {[BMI 25 to 29.9 OR waist circumference >88 cm (F) >102 cm (M)] AND 2 risk  factors} BMI measured in past 2 years?
    26. 29. Weight Loss Therapy <ul><li>Whenever possible, weight loss therapy should employ the combination of </li></ul><ul><li>Low-calorie/low-fat diets </li></ul><ul><li>Increased physical activity </li></ul><ul><li>Behavior modification </li></ul>
    27. 31. O – Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al. 2007) <ul><li>Blood pressure </li></ul><ul><li>Lipids </li></ul><ul><li>Diabetes </li></ul><ul><li>Aspirin </li></ul><ul><li>Beta-blockers (all women after MI, ACS, LV dysfunction) </li></ul><ul><li>ACE inhibitors/ ARBS – MI, CHF, DM </li></ul><ul><li>Aldosterone blockage – post MI with CHF </li></ul>
    28. 32. Blood Pressure <ul><li>Encourage optimal BP of <120/80 mmHg through lifestyle approaches </li></ul><ul><li>Pharmacotherapy when BP >=140/90 (or 130/80 if DM or CKD). Thiazide diuretics part of therapy for most pts. High risk women initially treated with beta blockers and/or ACE-I/ARB with addition of other drugs including diuretics to achieve goal </li></ul>
    29. 33. Blood Pressure Classification <80 and <120 Normal 80–89 or 120–139 Prehypertension 90–99 or 140–159 Stage 1 HTN > 100 or > 160 Stage 2 HTN DBP mmHg SBP mmHg BP Classification
    30. 34. 4-Year Progression To Hypertension: The Framingham Heart Study (<120/80 mm Hg) (130/85 mm Hg) (130-139/85-89 mm Hg) Vasan, et al. Lancet 2001;358:1682-86 Participants age 36 and older
    31. 36. JNC-7 New Features and Key Messages <ul><li>Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes. </li></ul><ul><li>Certain high-risk conditions are compelling indications for other drug classes. </li></ul><ul><li>Most patients will require two or more antihypertensive drugs to achieve goal BP. </li></ul><ul><li>If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic. </li></ul>
    32. 37. I have some bad news for you. While your cholesterol has remained the same, the research findings have changed.
    33. 39. Total Cholesterol Distribution: CHD vs Non-CHD Population Castelli WP. Atherosclerosis . 1996;124(suppl):S1-S9.  1996 Reprinted with permission from Elsevier Science. 35% of CHD Occurs in People with TC<200 mg/dL 150 200 Total Cholesterol (mg/dL) 250 300 No CHD CHD Framingham Heart Study—26-Year Follow-up
    34. 40. Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk of CHD Low HDL Smoking Hyperglycemia Hypertension No Other Risk Factors Schaefer EJ, adapted from the Framingham Heart Study CHD Risk Per 1000 (in 6 years) Serum Cholesterol (mg/dL)
    35. 41. Low HDL-C Levels Increase CHD Risk Even When Total-C Is Normal (Framingham) Risk of CHD by HDL-C and Total-C levels; aged 48–83 y Castelli WP et al. JAMA 1986;256:2835–2838 0 2 4 6 8 10 12 14 < 40 40–49 50–59  60 < 200 230–259 200–229  260 HDL-C (mg/dL) Total-C (mg/dL) 14-y incidence rates (%) for CHD 11.24 11.91 12.50 11.91 6.56 4.67 9.05 5.53 4.85 4.15 3.77 2.78 2.06 3.83 10.7 6.6
    36. 43. Primary and Secondary Prevention Trials With Statins Adapted from Ballantyne CM. Am J Cardiol. 1998;82:3Q-12Q . 2° prevention placebo 2° prevention statin 1° prevention placebo 1° prevention statin 0 5 10 15 20 25 30 80 90 100 110 120 130 140 150 160 170 180 190 200 LDL-C Achieved (mg/dL) AFCAPS AFCAPS WOSCOPS WOSCOPS CARE CARE LIPID LIPID 4S 4S Event Rate (%) HPS HPS
    37. 44. Statin Trials: Therapy Reduces Major Coronary Events in Women n = number of women enrolled. * 4S = primarily CHD death and nonfatal MI; CARE = coronary death, nonfatal MI, angioplasty, or bypass surgery; AFCAPS/TexCAPS = fatal/nonfatal MI, unstable angina, or sudden cardiac death. Miettinen TA et al. Circulation . 1997;96:4211-4218. Lewis SJ et al. J Am Coll Cardiol . 1998;32:140-146. Downs JR et al. JAMA . 1998;279:1615-1622. 4S (n=827) CARE (n=576) AFCAPS/TexCAPS (n=997) 2  Prevention 1  Prevention -50 -45 -40 -35 -30 -25 -20 -15 -10 -5 0 5 10 Major coronary events* -34 -46 -46 %  P =0.012 P =0.001
    38. 45. MRC/BHF Heart Protection Study (HPS): Eligibility <ul><li>Age 40–80 years </li></ul><ul><li>Increased risk of CHD death due to prior disease </li></ul><ul><ul><ul><li>Myocardial infarction or other coronary heart disease </li></ul></ul></ul><ul><ul><ul><li>Occlusive disease of noncoronary arteries </li></ul></ul></ul><ul><ul><ul><li>Diabetes mellitus or treated hypertension </li></ul></ul></ul><ul><li>Total cholesterol > 3.5 mmol/L (> 135 mg/dL) </li></ul><ul><li>Statin or vitamins not considered clearly indicated or contraindicated by patient’s own doctors </li></ul>Heart Protection Study Group. Lancet. 2002;360:7-22.
    39. 46. HPS: First Major Coronary Event 0.4 0.6 0.8 1.0 1.2 1.4 Nonfatal MI Coronary death Subtotal: MCE Coronary Noncoronary Subtotal: any RV Any MVE Coronary events Revascularizations Type of Major Vascular Event Statin- Allocated (n = 10269) Placebo- Allocated (n = 10267 ) 357 (3 .5%) 574 (5 .6%) 587 (5 .7%) 707 (6 .9%) 898 (8 .7%) 1212 (11 .8%) 513 (5 .0%) 725 (7 .1%) 450 (4 .4%) 532 (5 .2%) 939 (9 .1%) 1205 (11 .7%) 2033 (19 .8%) 2585 (25 .2%) 0.73 (0.67  0.79) P < 0.0001 0.76 (0.70  0.83) P < 0.0001 0 .76 (0.72  0.81) P < 0.0001 Statin Better Placebo Better Heart Protection Study Collaborative Group . Lancet. 2002;360:7  22.
    40. 47. HPS — Simvastatin: Vascular Events by Baseline LDL-C Event Rate Ratio (95% CI) Statin Better Statin Worse www.hpsinfo.org 0.76 (0.72 –0.81) P < 0.0001 358 (21.0%) 282 (16.4%) <100 871 (24.7%) 668 (18.9%) 100–129 2585 (25.2%) 2033 (19.8%) All patients 1356 (26.9%) 1083 (21.6%)  130 Placebo (n = 10,267) Statin (n = 10,269) Baseline LDL-C (mg/dL) 0.4 0.6 0.8 1.0 1.2 1.4
    41. 48. TNT: Changes in LDL-C by Treatment Group Final Screen 0 3 12 24 36 48 60 P <.001 Baseline Mean LDL-C (mmol/L) Mean LDL-C level = 101 mg/dL (2.6 mmol/L) Mean LDL-C level = 77 mg/dL (2.0 mmol/L) LaRosa et al. N Engl J Med. 2005;352:1425-1435. Mean LDL-C (mg/dL) Study Visit (Months) 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
    42. 49. TNT: Primary Efficacy Outcome Measure: Major Cardiovascular Events * * CHD death, nonfatal non – procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke. LaRosa et al. N Engl J Med. 2005;352:1425-1430. HR=0.78 (95% CI 0.69, 0.89); P <.001 Proportion of Patients Experiencing Major Cardiovascular Event 0 0.05 0.10 0.15 Atorvastatin 10 mg Atorvastatin 80 mg Relative risk reduction 22% 0 1 2 3 4 5 6 Time (Years) Mean LDL-C level = 77 mg/dL Mean LDL-C level = 101 mg/dL
    43. 50. Cholesterol Treatment Trialists’ (CCT) Collaboration: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis fo data from 90,056 participants in 14 randomized trials of statins (The Lancet 9/27/05) <ul><li>Over average 5 year treatment period (per mmol/L reduction—approx 40 mg/dl in LDL-C): </li></ul><ul><ul><li>12% reduction in all-cause mortality </li></ul></ul><ul><ul><li>19% reduction in coronary mortality </li></ul></ul><ul><ul><li>23% reduction in MI or CHD death </li></ul></ul><ul><ul><li>17% reduction in stroke </li></ul></ul><ul><ul><li>21% reduction in major vascular events </li></ul></ul><ul><ul><li>No difference in cancer incidence (RR=1.00). </li></ul></ul><ul><li>Statin therapy can safely reduce 5-year incidence of major coronary events, revascularization, and stroke by about 20% per mmol/L (about 38 mg/dl) reduction in LDL-C </li></ul>
    44. 51. Lipid Management (Mosca et al., 2007) <ul><li>Encourage through lifestyle approaches: </li></ul><ul><ul><li>LDL-C <100 mg/dl, HDL-C >50 mg/dl, triglycerides <150 mg/dl, and non-HDL-C <130 mg/dl </li></ul></ul><ul><li>In high risk women, utilize LDL-C lowering drug therapy to achieve LDL-C <100 mg/dl, with an optional reduction to <70 mg/dl in very-high-risk women with CHD </li></ul><ul><li>For other at-risk women, utilize LDL-C lowering drug therapy with lifestyle therapy according to NCEP ATP III when: </li></ul><ul><ul><li>LDL-C >=130 mg/dl if multiple risk factors and 10-20% risk </li></ul></ul><ul><ul><li>LDL-C >=160 mg/dl if muliple risk factors and <10% risk </li></ul></ul><ul><ul><li>LDL-C >=190 mg/dl regardless of presence of other risk factors </li></ul></ul>
    45. 52. Lipid Therapy (continued) <ul><li>Use niacin or fibrate therapy when HDL-C is low or non-HDL-C is elevated in high risk women after LDL-C goal is reached </li></ul><ul><li>Consider niacin or fibrate therapy when HDL-C is low or non-HDL-C is elevated after LDL-C goal is reached in women with multiple risk factors and 10-year risk 10-20% </li></ul>
    46. 53. When LDL-lowering drug therapy is employed in high-risk or moderately high risk patients, intensity of therapy should be sufficient to achieve a 30–40% reduction in LDL-C levels.
    47. 54. Grundy et al. Circulation. 2004;110:227-239. Doses of Statins Required to Attain 30-40% Reduction of LDL-C 39 10 Atorvastatin 39-45 5-10 Rosuvastatin 25-35 40-80 Fluvastatin 35-41 20-40 Simvastatin 34 40 Pravastatin 31 40 Lovastatin LDL Reduction, % Dose, mg/d
    48. 55. Questran ® Prescribing Information, Colestid ® Prescribing Information, WelChol ® Prescribing information, Niaspan ® Prescribing Information, Lopid ® Prescribing Information, TriCor ® Prescribing Information, Lipitor ® Prescribing Information, Zocor ® Prescribing Information, Mevaco ® r Prescribing Information, Lescol ® Prescribing Information, Pravacol ® Prescribing Information; Zetia ® Prescribing Information. Effect of Lipid-modifying Therapies TC–total cholesterol, LDL–low density lipoprotein, HDL–high density lipoprotein, TG–triglyceride. * Daily dose of 40mg of each drug, excluding rosuvastatin. Good  9%   1%   18%  13% Ezetimibe Good  14-29%  4-12%  25-50%  19-37% Statins* Good   30%  11-13%   4-21%   19% Fibrates (gemfibrozil) Poor to reasonable  30-70%  14-35%  10-20%  10-20% Nicotinic acid Poor Neutral or   3%   10-18%   7-10% Bile acid sequestrants Patient tolerability TG HDL LDL TC Therapy
    49. 56. Diabetes Mellitus <ul><li>Lifestyle and pharmacotherapy should be used as indicated in women with diabetes to achieve an HbA1C <7% </li></ul><ul><li>Insulin, metformin, TZDs, and DPP-4 inhibitors are important classes of drugs that aid in diabetes control </li></ul>
    50. 57. Diabetes as a CHD Risk Equivalent <ul><li>10-year risk for CHD  20% </li></ul><ul><li>High mortality with established CHD </li></ul><ul><ul><li>High mortality with acute MI </li></ul></ul><ul><ul><li>High mortality post acute MI </li></ul></ul><ul><ul><li>Prevalence has increased over 25% in past 15 years in California, paralleling 50% increase in overweight/obesity </li></ul></ul>
    51. 58. Collaborative Atorvastatin Diabetes Study (CARDS) <ul><li>2838 patients aged 40-75 with type 2 diabetes, no prior CVD, but at least 1 of the following: retinopathy, albuminuria, smoking, or hypertension </li></ul><ul><li>Randomization to 10 mg atorvastatin or placebo </li></ul><ul><li>Mean follow-up 3.9 years </li></ul><ul><li>Reduction in all CVD events of 37% (p=0.001), all cause mortality 27% (p=0.059). CHD events reduced 36% and stroke 48%. </li></ul>Colhoun HM et al., The Lancet 2004; 364: 685-696
    52. 59. Probability of Death From CHD in Patients With NIDDM and in Nondiabetic Patients, With and Without Prior MI Kaplan-Meier estimates Haffner SM et al. N Engl J Med 1998;339:229–234 0 1 2 3 4 5 6 7 8 0 20 40 60 80 100 Nondiabetic subjects without prior MI Diabetic subjects without prior MI Nondiabetic subjects with prior MI Diabetic subjects with prior MI Years Survival (%)
    53. 60. Framingham Heart Study 30-Year Follow-Up: CVD Events in Patients With Diabetes (Ages 35-64) 10 9 20 11 9 6 38 19 3* 30 0 2 4 6 8 10 Age-adjusted annual rate/1,000 Men Women Total CVD CHD Cardiac failure Intermittent claudication Stroke Risk ratio P <0.001 for all values except * P <0.05. Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease. Ruderman N et al, eds. Oxford; 1992.
    54. 61. The Metabolic Syndrome Insulin Resistance Hypertension Type 2 Diabetes Disordered Fibrinolysis Complex Dyslipidemia TG, LDL HDL Endothelial Dysfunction Systemic Inflammation Athero- sclerosis Visceral Obesity Adapted from the ADA. Diabetes Care. 1998;21:310-314; Pradhan AD et al. JAMA. 2001;286:327-334.
    55. 62. ATP III: The Metabolic Syndrome* *Diagnosis is established when  3 of these risk factors are present. † Abdominal obesity is more highly correlated with metabolic risk factors than is  BMI. ‡ Some men develop metabolic risk factors when circumference is only marginally ; ** new ADA guideline for impaired fasting glucose >=100 mg/dl increased. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 2001;285:2486-2497. © 2001, Professional Postgraduate Services ® www.lipidhealth.org <40 mg/dL <50 mg/dL Men Women >102 cm (>40 in) >88 cm (>35 in) Men Women **  100 mg/dL Fasting glucose  130/  85 mm Hg or on meds Blood pressure HDL-C  150 mg/dL TG Abdominal obesity † (Waist circumference ‡ ) Defining Level Risk Factor
    56. 63. Cardiovascular Disease (CVD) and Total Mortality: US Men and Women Ages 30-74 (age, gender, and risk-factor adjusted Cox regression) NHANES II Follow-Up (n=6255)(Malik and Wong, et al., Circulation 2004; 110: 1245-1250 ) * p<.05, ** p<.01, **** p<.0001 compared to none * *** *** *** ** *** *** *** *** *** ***
    57. 64. Aspirin <ul><li>Aspirin therapy (75 to 325 mg/d) should be used in high-risk women unless contraindicated or intolerated (where clopidogrel should be substituted) </li></ul><ul><li>Other at risk or healthy women: for those aged >=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and benefit for stroke/MI prevention is likely to outweigth GI bleeding/hemorrhagic stroke risk. </li></ul>
    58. 65. H – Highest Priority for Therapy is for Women at Highest Risk <ul><li>Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the following Class I recommendations: </li></ul><ul><ul><li>ACE inhibitor therapy (if coughing, subst. ARB) </li></ul></ul><ul><ul><li>Aspirin therapy (baby aspirin or maximum dose of 162 mg) unless contraindicated </li></ul></ul><ul><ul><li>Beta-blocker therapy in those with prior MI or current angina </li></ul></ul><ul><ul><li>Statin therapy </li></ul></ul><ul><ul><li>Niacin or fibrate therapy if low HDL present </li></ul></ul><ul><ul><li>Fibrates to lower triglycerides and improve HDL </li></ul></ul><ul><ul><li>Warfarin in those with atrial fibrillation unless contradindicated </li></ul></ul>
    59. 66. A – Avoid “Class III” Interventions (Not proven useful or effective / may be harmful) <ul><li>Combined estrogen and progestin therapy, and *estrogen monotherapy since associated with increased risk of CVD </li></ul><ul><li>Selective estrogen-receptor modulators (SERMs) also not recommended </li></ul><ul><li>Antioxidant supplements including vigtamin E, C, and beta-carotene </li></ul><ul><li>Folic acid with or without B6 or B12 supplementation </li></ul><ul><li>Aspirin for MI prevention in women aged <65 years </li></ul>
    60. 67. Vitamins: Major Vascular Events Heart Protection Study Collaborative Group. Lancet. 2002;360:23 –33 . Risk Ratio and 95% CI Vitamin Better Vitamin Worse 1.00 (0.94 –1.06) P > 0.9 Vitamins (n = 10,269) Placebo (n = 10,267) 2312 (22.5%) 2306 (22.5%) Any of the above 1086 1058 Revascularization 518 511 Any stroke 1047 1063 Major coronary Vascular Event 0.4 0.6 0.8 1.0 1.2 1.4
    61. 68. Does Hormone Replacement Therapy Prevent Heart Disease <ul><li>Epidemiologic studies over the past several decades together have shown approximately a 50% lower risk in women randomized to estrogen replacement therapy vs. placebo </li></ul><ul><li>Even the Nurses’ Health Study showed those on estrogen/progestin to have approximately a 60% lower risk of heart disease events </li></ul>
    62. 69. Heart and Estrogen/Progestin Replacement Study (HERS): Secondary Prevention of CHD in Women <ul><li>Randomized, placebo-controlled trial of E/P therapy vs. placebo in 2763 women with CHD; average age 67 years </li></ul><ul><li>Treatment was 0.625 mg CEE + 2.5 mg medroxyprogesterone daily for 4 years </li></ul><ul><li>Primary endpoint: nonfatal MI and CHD death </li></ul><ul><li>Secondary endpoints: CABG, PTCA, unstable angina, CHF, PVD, TIA </li></ul>JAMA 1998;280:605-613
    63. 70. HERS Results <ul><li>No statistically significant difference between HRT and placebo in both primary and secondary endpoints after 4 years. </li></ul><ul><li>Within first year, greater incidence in CHD events in HRT group. In years 3 and 4, lower CHD events in HRT group compared to placebo. </li></ul><ul><li>HRT lowered LDL 11% and increased HDL 10% compared to placebo. </li></ul><ul><li>Approximately 50% of randomized women were on lipid-lowering drugs. </li></ul><ul><li>Higher incidence of VTE and cholelithiasis in HRT group. </li></ul>JAMA 1998;280:605-613
    64. 71. More Bad News: The Women’s Health Initiative <ul><li>Over 160,000 women nationwide, aged 50-79 and postmenopausal have participated in various components (observational, dietary modification, and HRT clinical trials)—over 3,000 at UCI </li></ul><ul><li>The Estrogen/Progestin component of the HRT clinical trial involving 16,608 women nationwide was discontinued prematurely in Spring 2002 after 5.2 years of follow-up (instead of 8.5 years). </li></ul>
    65. 72. WHI Estrogen/Progestin and Estrogen Only Results <ul><li>Those randomized to estrogen/progestin compared to placebo and statistically significant increased risks: </li></ul><ul><ul><li>Breast cancer 26% (8/10,000 person years) </li></ul></ul><ul><ul><li>Total coronary heart disease 29% (7/10,000 person years) </li></ul></ul><ul><ul><li>Stroke 41% (8/10,000 person years) </li></ul></ul><ul><ul><li>Pulmonary emobolism 2.1 X (8/10,000 person years) </li></ul></ul><ul><ul><li>Protective for colorectal cancer (37% lower) and hip fracture (34% lower): no effect endometrial cancer or total mortality </li></ul></ul><ul><ul><li>JAMA. 2002 Jul 17;288(3):321-33. </li></ul></ul><ul><li>Estrogen-only arm was also recently discontinued in December 2003 and was associated with a 39% increased risk of stroke (12 excess strokes per 10,000 person years) and 12% significant increased risk of cardiovascular events. JAMA. 2004 Apr 14;291(14):1701-12. </li></ul>
    66. 75. For More Information about Preventing Heart Disease: Preventive Cardiology, 2 nd ed. from McGraw-Hill ….. For more information, see the UCI Heart Disease Prevention Website at www.heart.uci.edu

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