Coronary Heart Disease in Women Karol E. Watson, MD, PhD Assistant Professor of Medicine/ Division of Cardiology Co-direct...
Statistics <ul><li>Heart Disease and Stroke  </li></ul><ul><ul><li>First and third leading causes of death in US </li></ul...
Cardiovascular Disease Mortality Trends  for Males and Females  United States: 1979-2003 Source: CDC/NCHS.  0
Hospital Discharges for Heart Failure by Sex -  United States: 1979-2003 Source: National Hospital Discharge Survey, CDC/N...
Source: NCHS and NHLBI.  These data include coronary heart disease, heart failure, stroke and hypertension. Prevalence of ...
Incidence of cardiovascular disease by age and sex Source: FHS, 1980-2003. NHLBI.
Source: NHLBI’s ARIC surveillance study, 1987-2000. Annual  rate of first heart attacks by age, sex and race ( ARIC: 1987-...
Note: Hospital discharges include people discharged alive, dead and status unknown.. Source: NHDS, NCHS and NHLBI. Hospita...
Women and Heart Disease
Heart Disease is the #1 Killer of Women <ul><li>Coronary heart disease is the single leading cause of death and a signific...
“ Breast Cancer is the REAL issue!” <ul><li>Who cares about heart disease doc…I am more concerned about: </li></ul><ul><li...
In perspective: <ul><li>1 in 2 women will die of heart disease. </li></ul><ul><li>1 in 25 women will die of breast cancer....
CHD Mortality in Younger Women Women  under  65 suffer the highest relative sex-specific CHD mortality
Coronary Heart Disease in Women <ul><li>Presentation and differences from men </li></ul><ul><li>2/3 of women who die sudde...
Nationally:  The Problem – AWARENESS <ul><li>Perception </li></ul><ul><li>67% knowledgeable that chest pain can be heart d...
Causes of Confusion: <ul><li>Women may experience more dizziness, nausea, indigestion, and  fatigue  than men.  </li></ul>...
Women and Heart Disease Risk Factors
Source: NCHS and NHLBI.  Trends in total cholesterol among adolescents ages 12-17 by race and sex  (NHES: 1966-70; NHANES:...
Non-modifiable Risk Factors <ul><li>Age > 55 </li></ul><ul><ul><li>CAD rates are 2-3x’s higher in postmenopausal women </l...
The #1 Preventable Risk- Smoking <ul><li>A. 50% of heart attacks among women are due to smoking. Smokers tend to have thei...
SMOKING: <ul><li>Stop!!!!! (avg. attempt = 8 times) </li></ul><ul><li>Women who have other smokers in their household have...
Hypertension <ul><li>65% of all hypertension remains either undetected or inadequately treated.  </li></ul><ul><li>People ...
Women and HTN—JNC VII <ul><li>The relationship bet. BP and CV events is continuous, consistent and independent of other ri...
Risk Factors: Diabetes  <ul><li>Diabetes increases the risk of  CHD 3-7 X in women  versus 2-3 X in men. </li></ul><ul><li...
Cholesterol <ul><li>More than 55 million women (45million men) have TC>200. </li></ul><ul><li>Check cholesterol at least o...
Lifestyle Modification for HTN 2-4 mm Hg 2-12 oz beer, 1 10oz wine, 3 oz 80proof whiskey in men Reduced EtOH (1/2 for wome...
Glycemic control In Diabetes <ul><li>Treatment of hyperglycemia has been shown to reduce or delay complications of diabete...
Cholesterol <ul><li>Women at high risk should be considered for statin therapy regardless of cholesterol-LDL levels. </li>...
How we’ve changed our thinking about Primary Prevention in Women <ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors  <...
HERS: Combined HT Does Not Decrease All-Cause Mortality Hulley S, et al.  JAMA.  1998;280:605–613. Incidence (%) Follow-up...
Estrogen + Progestin and Disease in WHI* Coronary Heart Disease HR = 1.29 95% nCI. 1.02–1.63 95% aCI. 0.85–1.97 Estrogen  ...
24% Increase  Breast Cancer Also: DVTs Fracture Reduction (Hip 23%) STOPPED Early, Clear Harm 24% Increase   CHD 31% Incre...
Summary of WHI Estrogen-Alone Results <ul><li>Event Relative Hazard 95% CI </li></ul><ul><li>  </li></ul><ul><li>Inv. Brea...
Also: DVTs Fracture Reduction (Hip 39%) STOPPED Early, suggestion of harm Neutral for   CHD Neutral for breast cancer 39% ...
<ul><li>Analysis of 24,317 women 50-79 years old in WHI </li></ul><ul><ul><li>whose age at menopause could be defined </li...
Current research centers around the question:  Does estrogen mean different things in different vessels?
How we’ve changed our thinking <ul><li>Hormone Therapy </li></ul><ul><ul><li>WHI - Combined hormone therapy increases card...
NHANES III: Age-Adjusted Prevalence of ≥3 Risk Factors for the Metabolic Syndrome* *Criteria based on ATP III; diabetics w...
Elevated Triglycerides Increase CHD Risk Relative Risk for CHD Men Women For every increase in serum TG level of 89 mg/dL,...
CVD Events in Patients With Diabetes: Framingham Heart Study 30-Year Follow-Up *.001< P <.01;  † P <.05;  ‡ For diabetic p...
Risk of Stroke With Metabolic Syndrome, Stratified by Gender   Boden-Albala BM et al. American Academy of Neurology Annual...
<ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors  </li></ul><ul><ul><li>Triglycerides, diabetes, and the metabolic s...
Meta-analysis from Cholesterol Clinical Trialists (CCT) Collaboration Cholesterol Clinical Trialists Collaboration.  Lance...
Physicians’ Health Study (PHS) Aspirin Evidence: Primary Prevention in Men 22,071 men randomized to aspirin (325mg QOD) fo...
Women's Health Study:  Low-Dose Aspirin in Primary Prevention Trial <ul><li>End points (mean, 10.1 yrs): </li></ul><ul><ul...
 
Womens’ Health Study (WHS) Aspirin : Primary Prevention in Women Cumulative  Incidence of MI Placebo Aspirin P=0.83 Ridker...
 
 
Conclusions <ul><li>In this large, primary-prevention trial among women, aspirin (50 mg/d) lowered the risk of stroke with...
Aspirin Evidence: Primary Prevention BDT, 1988 Combined PPP, 2001 HOT, 1998 TPT, 1998 PHS, 1989 RR of MI in Men 1.0 2.0 5....
<ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors  </li></ul><ul><li>Preventive Medications </li></ul><ul><ul><li>Sta...
Women’s Health Initiative Study Reducing Total Fat Intake <ul><li>Study the effect of low-fat, high fruit, vegetable, and ...
WHI – Heart Disease:  RESULTS <ul><li>No reduction in risk of MI or CHD death </li></ul><ul><li>Small but significant impr...
WHI :  What went wrong? <ul><li>Dietary pattern reduced ALL types of fat  </li></ul><ul><li>Diet designed for heart diseas...
Trans Fatty Acids and CHD Risk in Women Sun et. al.   Circulation  2007: 115 <ul><li>Blood samples from 32,836 NHS subject...
<ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors  </li></ul><ul><li>Preventive Medications </li></ul><ul><li>Lifesty...
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Coronary Heart Disease in Women (Dr. Karol E. Watson)

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  • Optimal level of hdl-c&gt;50 Intiate niacin or fibrate therapy for low hdl or elevated nonhdl in high risk women is a class 1 recommendation
  • The metabolic syndrome is quite prevalent among women, especially among sub-groups such as African-Americans and Mexican-American women. And since 1 out of 5 Americans will have the metabolic syndrome, we need to identify this more rigorously in our practice so that we can institute appropriate treatment. There is also an ICD 9 code for metabolic syndrome to use for testing and treatment.
  • Key Point 1: In this meta-analysis of 17 prospective studies, we once again can see a clear CHD risk in patients with elevated TGs. Key Point 2: For every increase in TG level of 89 mg/dl the risk of CHD is increased 30 percent in men and 69 percent in women . Key Point 3: Elevated TG levels are a clear threat to men and serious health risk for women. Reference: Castelli WP. Can J Cardiol. 1988;4(suppl A):5A-10A. Hokanson JE. Curr. Cardiol. Rep. 2002;4:488-493.
  • It is well documented in epidemiology studies, such as the Framingham Heart Study, that patients with diabetes have increased risk for various types of CVD. In the 30-year follow-up of the Framingham Heart Study, the relative risks for all CVD, CHD, cardiac failure, and intermittent claudication were significantly greater for women with diabetes than for men with diabetes aged 35 to 64. The highest risks in both sexes were for cardiac failure and intermittent claudication. Stroke was the only event for which men with diabetes were at higher risk than women. 15 15. Wilson PWF, Kannel WB. Epidemiology of hyperglycemia and atherosclerosis. In: Ruderman N, Williamson J, Brownlee M, eds . Hyperglycemia, Diabetes, and Vascular Disease. New York, NY: Oxford University Press; 1992:21-29.
  • The Physicians&apos; Health Study was a randomized, double-blind, placebo-controlled trial designed to determine whether primary prevention with aspirin (325 mg every other day) was associated with a reduction in cardiovascular disease mortality. The trial included 22,071 participants, with an average follow-up of 60 months. Aspirin use was associated with a 44% reduction in the risk of MI, however, this effect was mainly present in men &gt;50 years of age. There was no reduction in cardiovascular mortality (RR 0.96; 95% CI 0.60 to 1.54). A slightly increased risk of stroke was observed among those taking aspirin (p=NS). This trend was noted primarily in the subgroup with hemorrhagic stroke (RR 2.14; 95% CI [0.96 to 4.77]; p=0.06). The relative risk of ulcer in the aspirin group was 1.22 (169 in the aspirin group as compared with 138 in the placebo group; 95% CI [0.98 to 1.53]; p=0.08). Overall: Use of aspirin in men (especially &gt;50 years of age) for primary prevention was associated with a reduced risk of MI.
  • The Women&apos;s Health Study was a randomized, double-blind, placebo-controlled trial designed to determine whether primary prevention with low dose aspirin (100 mg every other day) was associated with a reduction in CV events (nonfatal MI, nonfatal stroke, or death from a cardiovascular cause). The trial included 39,876 healthy women &gt; 45 years of age, with a mean follow-up of 10 years. Aspirin use was associated with a 17% reduction in the risk of stroke (RR 0.83; 0.69-0.99; P=0.04), a 24% reduction in the risk of ischemic stroke (RR 0.76; 0.63-0.93; P=0.009), and a nonsignificant increase in the risk of hemorrhagic stroke (RR 1.24; 0.82-1.87; P=0.31). Aspirin had no effect on the risk of fatal or nonfatal myocardial infarction (RR 1.02; 0.84-1.25; P=0.83) or death from CV causes (RR 0.95; 0.74-1.22; P=0.68). Among women &gt; 65 years of age, however, aspirin use was associated with a reduction of major cardiovascular events (RR 0.74; 0.59-0.92; P=0.008) and risk of ischemic stroke (RR 0.70; 0.49-1.00; P=0.05). GI bleeding requiring transfusion was more frequent in the aspirin group (RR 1.40; 1.07-1.83; P=0.02). Overall: The routine use of aspirin in low risk women (&lt;10% 10 year risk of a CHD event) should generally be avoided. Aspirin use in women &gt; 65 reduced the risk of cardiovascular events.
  • This is a summary of the data looking at aspirin use in primary prevention.
  • Coronary Heart Disease in Women (Dr. Karol E. Watson)

    1. 1. Coronary Heart Disease in Women Karol E. Watson, MD, PhD Assistant Professor of Medicine/ Division of Cardiology Co-director, UCLA Program in Preventive Cardiology David Geffen School of Medicine at UCLA
    2. 2. Statistics <ul><li>Heart Disease and Stroke </li></ul><ul><ul><li>First and third leading causes of death in US </li></ul></ul><ul><ul><li>Accounts for more than 40% of all deaths </li></ul></ul><ul><li>About 95,000 Americans die of heart disease or stroke each year </li></ul><ul><ul><li>Amounts to one death every 33 seconds </li></ul></ul><ul><li>Heart Disease is the leading cause of disability among working adults </li></ul>
    3. 3. Cardiovascular Disease Mortality Trends for Males and Females United States: 1979-2003 Source: CDC/NCHS. 0
    4. 4. Hospital Discharges for Heart Failure by Sex - United States: 1979-2003 Source: National Hospital Discharge Survey, CDC/NCHS and NHLBI. 0 100 200 300 400 500 600 700 79 80 85 90 95 00 03 Years Discharges in Thousands Male Female
    5. 5. Source: NCHS and NHLBI. These data include coronary heart disease, heart failure, stroke and hypertension. Prevalence of cardiovascular diseases in adults by age and sex ( NHANES: 1999-2004).
    6. 6. Incidence of cardiovascular disease by age and sex Source: FHS, 1980-2003. NHLBI.
    7. 7. Source: NHLBI’s ARIC surveillance study, 1987-2000. Annual rate of first heart attacks by age, sex and race ( ARIC: 1987-2000).
    8. 8. Note: Hospital discharges include people discharged alive, dead and status unknown.. Source: NHDS, NCHS and NHLBI. Hospital discharges for heart failure by sex (United States: 1979-2004).
    9. 9. Women and Heart Disease
    10. 10. Heart Disease is the #1 Killer of Women <ul><li>Coronary heart disease is the single leading cause of death and a significant cause of morbidity among American women. </li></ul><ul><li>In 1997 CHD claimed the lives of 502,938 women (men had less deaths) </li></ul><ul><li>Since 1984, CVD has killed more American women than men each year. </li></ul>
    11. 11. “ Breast Cancer is the REAL issue!” <ul><li>Who cares about heart disease doc…I am more concerned about: </li></ul><ul><li>BREAST CANCER and lung cancer!” </li></ul><ul><li>In a recent survey, 75% of women identified cancer as their leading cause of death… </li></ul>
    12. 12. In perspective: <ul><li>1 in 2 women will die of heart disease. </li></ul><ul><li>1 in 25 women will die of breast cancer. </li></ul>
    13. 13. CHD Mortality in Younger Women Women under 65 suffer the highest relative sex-specific CHD mortality
    14. 14. Coronary Heart Disease in Women <ul><li>Presentation and differences from men </li></ul><ul><li>2/3 of women who die suddenly have no previously recognized symptoms. </li></ul><ul><li>Women are more prone to non-cardiac chest pain….. </li></ul><ul><li>In fact they may experience little or no squeezing chest pain in the center of the chest, lightheadedness, fainting, or shortness of breath with an MI </li></ul>Source: Milner Am J Cardiol 1999;84:396
    15. 15. Nationally: The Problem – AWARENESS <ul><li>Perception </li></ul><ul><li>67% knowledgeable that chest pain can be heart disease </li></ul><ul><li><10% knowledgeable that SOB, nausea, indigestion can be heart disease </li></ul><ul><li>Reality </li></ul><ul><li>chest pain is the presenting symptom in <50% of women </li></ul><ul><li>Almost half of MIs in women present with SOB, nausea, indigestion, fatigue and shoulder pain </li></ul>
    16. 16. Causes of Confusion: <ul><li>Women may experience more dizziness, nausea, indigestion, and fatigue than men. </li></ul><ul><li>Women are more likely to have neck, arms, back and shoulder pain. </li></ul>
    17. 17. Women and Heart Disease Risk Factors
    18. 18. Source: NCHS and NHLBI. Trends in total cholesterol among adolescents ages 12-17 by race and sex (NHES: 1966-70; NHANES: 1971-74 and 1988-94).
    19. 19. Non-modifiable Risk Factors <ul><li>Age > 55 </li></ul><ul><ul><li>CAD rates are 2-3x’s higher in postmenopausal women </li></ul></ul><ul><li>Family history </li></ul><ul><ul><li>CHD in primary 1 st degree relative male<55 or female<65 </li></ul></ul>
    20. 20. The #1 Preventable Risk- Smoking <ul><li>A. 50% of heart attacks among women are due to smoking. Smokers tend to have their first heart attack 10 years earlier than nonsmokers. </li></ul><ul><li>B. If you smoke, you are 4-6x’s more likely to suffer a heart attack and increase your risk of a stroke. </li></ul><ul><li>C. Women who smoke and take OCP’s increase their risk of heart disease 30x’s. </li></ul>
    21. 21. SMOKING: <ul><li>Stop!!!!! (avg. attempt = 8 times) </li></ul><ul><li>Women who have other smokers in their household have a 2.5 X's greater likelihood of relapse. Circulation 2002:106 </li></ul><ul><li>Smoking cessation was associated with a 36% reduction in mortality among patients with CHD. JAMA 2003:290 </li></ul>
    22. 22. Hypertension <ul><li>65% of all hypertension remains either undetected or inadequately treated. </li></ul><ul><li>People who are normotensive at 55 have a 90% lifetime risk of developing HTN. </li></ul><ul><li>Prevalence increases with age and women live longer- hypertension is more common in females. </li></ul><ul><li>HTN is more common with OCP and obesity. </li></ul>
    23. 23. Women and HTN—JNC VII <ul><li>The relationship bet. BP and CV events is continuous, consistent and independent of other risk factors. </li></ul><ul><li>The higher the BP the greater the chance of MI, CHF, stroke, and kidney disease. </li></ul><ul><li>Can try to achieve good BP through lifestyle changes. </li></ul>
    24. 24. Risk Factors: Diabetes <ul><li>Diabetes increases the risk of CHD 3-7 X in women versus 2-3 X in men. </li></ul><ul><li>Diabetic women who smoke have a 84% higher risk of developing stroke than nonsmokers. </li></ul><ul><li>2 of 3 people with diabetes die from CHD or stroke. </li></ul>
    25. 25. Cholesterol <ul><li>More than 55 million women (45million men) have TC>200. </li></ul><ul><li>Check cholesterol at least once q 5yr’s starting at age 20. </li></ul><ul><li>36 Million people in the US should be taking a statin according to guidelines, but only 11 million are. </li></ul>
    26. 26. Lifestyle Modification for HTN 2-4 mm Hg 2-12 oz beer, 1 10oz wine, 3 oz 80proof whiskey in men Reduced EtOH (1/2 for women) 4-9 mm Hg 30 mins of aerobic 4x’s a week Physical activity 2-8 mm Hg <2.4 g every day Sodium restriction 8-14 mm Hg Fruits, veges, low-fat dairy products, less fat DASH 5-20 mm Hg per 10kg wt loss Goal of BMI 18-25 Waist <35inches Weight reduction Expected systolic reduction Recommendation Modification
    27. 27. Glycemic control In Diabetes <ul><li>Treatment of hyperglycemia has been shown to reduce or delay complications of diabetes such as retinopathy, neuropathy, and nephropathy </li></ul><ul><li>keep HBA1C < 6.5% </li></ul><ul><li>FPG <100 </li></ul><ul><li>2 hour 75g GTT-Impaired glucose tolerance- 140-199. </li></ul>
    28. 28. Cholesterol <ul><li>Women at high risk should be considered for statin therapy regardless of cholesterol-LDL levels. </li></ul><ul><li>Statins have surpassed all other classes of agents in reducing the incidence of the major adverse outcomes of death, MI, and stroke. NEJM 350:15 April 8, 2004 </li></ul>
    29. 29. How we’ve changed our thinking about Primary Prevention in Women <ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors </li></ul><ul><li>Preventive Medications </li></ul><ul><li>Lifestyle Interventions </li></ul>
    30. 30. HERS: Combined HT Does Not Decrease All-Cause Mortality Hulley S, et al. JAMA. 1998;280:605–613. Incidence (%) Follow-up, y (no. at risk) 0 5 10 15 0 (2763) 1 (2720) 2 (2666) 3 (2595) 4 (1590) 5 (130) Estrogen-Progestin Placebo
    31. 31. Estrogen + Progestin and Disease in WHI* Coronary Heart Disease HR = 1.29 95% nCI. 1.02–1.63 95% aCI. 0.85–1.97 Estrogen + Progestin Placebo Cumulative Hazard Cumulative Hazard Stroke HR = 1.41 95% nCI. 1.07–1.85 95% aCI. 0.86–2.31 Invasive Breast Cancer HR = 1.26 95% nCI. 1.00–1.59 95% aCI. 0.83–1.92 Pulmonary Embolism HR = 2.13 95% nCI. 1.39–3.25 95% aCI. 0.99–4.56 Cumulative Hazard Hip Fracture HR = 0.66 95% nCI. 0.45–0.98 95% aCI. 0.33–1.33 Colorectal Cancer HR = 0.63 95% nCI. 0.43–0.92 95% aCI. 0.32–1.24 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Time (y) Time (y) 0.03 0.01 0.02 0 0.03 0.01 0.02 0 0.03 0.01 0.02 0
    32. 32. 24% Increase Breast Cancer Also: DVTs Fracture Reduction (Hip 23%) STOPPED Early, Clear Harm 24% Increase CHD 31% Increase Stroke Risks Benefits JAMA. 2002;288:321-333 Stopped 3.3 yrs early 111% Increase Pulmonary Emboli 39% Reduction Colorectal Cancer WHI E+P Trial Findings, July 2002 (avg 5.2 y) 105% Increase Dementia
    33. 33. Summary of WHI Estrogen-Alone Results <ul><li>Event Relative Hazard 95% CI </li></ul><ul><li> </li></ul><ul><li>Inv. Breast Cancer 0.77 0.59-1.01 </li></ul><ul><li>CHD 0.91 0.75-1.12 </li></ul><ul><li>Hip Fracture 0.61 0.41-0.91* </li></ul><ul><li>All Fractures 0.70 0.63-0.70* </li></ul><ul><li>Colorectal Cancer 1.08 0.75-1.15 </li></ul><ul><li>_____________________________________________ </li></ul><ul><li>* p<.05 </li></ul><ul><li>JAMA, 4/14/04 </li></ul>
    34. 34. Also: DVTs Fracture Reduction (Hip 39%) STOPPED Early, suggestion of harm Neutral for CHD Neutral for breast cancer 39% Increase Stroke Risks Benefits JAMA 2004;291:2947-58 Stopped 1.7 yrs early 34% Increase Pulmonary Emboli WHI E Alone Trial Findings, 2004 (avg 6.8 y) 49% Increase Dementia
    35. 35. <ul><li>Analysis of 24,317 women 50-79 years old in WHI </li></ul><ul><ul><li>whose age at menopause could be defined </li></ul></ul><ul><ul><li>stratified into 3 groups: 50-59/ 60-60 /70-79 y.o. </li></ul></ul><ul><li>CHD, stroke & mortality rates analyzed </li></ul><ul><li>Stroke was increased in all women, regardless of age at menopause or E vs. E + P </li></ul><ul><li>CHD was decreased in women who took E alone vs. E + P (0.95 vs. 1.23 p=0.02) </li></ul><ul><li>In hormone users </li></ul><ul><ul><li>HR for CHD if < 10 years from menopause = 0.76 </li></ul></ul><ul><ul><li>HR for CHD if 10-20 from menopause = 1.10 </li></ul></ul><ul><ul><li>HR for CHD if >20 years from menopause = 1.28 </li></ul></ul>Estrogen in the early menopausal years Rossouw, J. E. et al. JAMA 2007;297:1465-1477.
    36. 36. Current research centers around the question: Does estrogen mean different things in different vessels?
    37. 37. How we’ve changed our thinking <ul><li>Hormone Therapy </li></ul><ul><ul><li>WHI - Combined hormone therapy increases cardiovascular risk overall * (but may be safe/?beneficial in the early menopausal years) </li></ul></ul><ul><ul><li>WHI - Estrogen only therapy is neutral on CHD </li></ul></ul><ul><li>Risk Factors </li></ul><ul><li>Preventive Medications </li></ul><ul><li>Lifestyle Interventions </li></ul>
    38. 38. NHANES III: Age-Adjusted Prevalence of ≥3 Risk Factors for the Metabolic Syndrome* *Criteria based on ATP III; diabetics were included in diagnosis; overall unadjusted prevalence 21.8%. Ford ES et al. JAMA . 2002;287:356-359. 24.8 16.4 28.3 22.8 25.7 35.6 Prevalence( %) White African American Mexican American Men Women 0 5 10 15 20 25 30 35 40
    39. 39. Elevated Triglycerides Increase CHD Risk Relative Risk for CHD Men Women For every increase in serum TG level of 89 mg/dL, risk of CHD increases 30% in men and 69% in women 13.14 Framingham Heart Study Meta-Analysis of 17 Prospective Studies
    40. 40. CVD Events in Patients With Diabetes: Framingham Heart Study 30-Year Follow-Up *.001< P <.01; † P <.05; ‡ For diabetic patient relative to nondiabetic patient aged 35 – 64 years. Wilson et al. In: Ruderman et al, eds. Hyperglycemia, Diabetes, and Vascular Disease . 1992:21-29. Relative Risk Ratio ‡ Women Total CVD * * CHD * * Cardiac Failure * * Intermittent Claudication * * Stroke † 0 2 4 6 8 10 12 Men
    41. 41. Risk of Stroke With Metabolic Syndrome, Stratified by Gender Boden-Albala BM et al. American Academy of Neurology Annual Meeting. Mar 29-Apr 5, 2003: Honolulu, HI. 0.0001 1.4-3.5 2.2 Women NS 0.5-1.7 0.9 Men p 95% CI Hazard ratio Gender
    42. 42. <ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors </li></ul><ul><ul><li>Triglycerides, diabetes, and the metabolic syndrome are greater risks for women as compared to men </li></ul></ul><ul><li>Preventive Medications </li></ul><ul><li>Lifestyle Interventions </li></ul>How we’ve changed our thinking about Primary Prevention in Women
    43. 43. Meta-analysis from Cholesterol Clinical Trialists (CCT) Collaboration Cholesterol Clinical Trialists Collaboration. Lancet . 2005;366:1267. Groups Post MI Other CHD None Sex Male Female 1681 (11.7%) 568 (8.7%) 1088 (4.5%) 2207 (15.4%) 744 (11.4%) 1469 (6.1%) 3630 (10.6%) 790 (7.3%) 2686 (7.8%) 651 (6.1%) Events Treatment Control 45,002 45,054 RR Heterogeneity/ trend test 0.78 (0.74-0.84) 0.77 (0.68-0.87) 0.72 (0.66-0.80) 0.76 (0.72-0.80) 0.82 (0.73-0.93) 0.5 1.0 1.5 Control better Treatment better P=0.2 P=0.1
    44. 44. Physicians’ Health Study (PHS) Aspirin Evidence: Primary Prevention in Men 22,071 men randomized to aspirin (325mg QOD) followed for 5 years Aspirin significantly reduces the risk of MI in men Physicians’ Health Study Research Group. NEJM 1989;321:129-35 CI=Confidence interval, MI=Myocardial infarction
    45. 45. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial <ul><li>End points (mean, 10.1 yrs): </li></ul><ul><ul><li>Combined end point of nonfatal MI, nonfatal stroke, or total cardiovascular death </li></ul></ul><ul><ul><li>Incidence of total malignant neoplasms of epithelial cell origin </li></ul></ul>Ridker PM. Presented at: 54th Annual Scientific Session of the American College of Cardiology; March 7, 2005; Orlando, Fla. Ridker PM, et al. N Engl J Med . 2005;352. 39,876 initially healthy † women, aged  45 yrs Randomized, blinded, factorial Low-Dose Aspirin 100 mg on alternate days n=19,934 Placebo n=19,942 † No history of coronary heart disease, cerebrovascular disease, cancer (except nonmelanoma skin cancer), or other major chronic illness; no history of side effects to any of the study medications; not taking aspirin or nonsteroidal anti-inflammatory medications (NSAIDs) more than once a week (or were willing to forgo their use during the trial); not taking anticoagulants or corticosteroids; and not taking individual supplements of vitamin A, E, or beta carotene more than once a week.
    46. 47. Womens’ Health Study (WHS) Aspirin : Primary Prevention in Women Cumulative Incidence of MI Placebo Aspirin P=0.83 Ridker P et al. NEJM 2005;352:1293-304 MI=Myocardial infarction Years 39,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years Aspirin does not reduce the risk of MI in low risk women
    47. 50. Conclusions <ul><li>In this large, primary-prevention trial among women, aspirin (50 mg/d) lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes. In the subgroup of women > 65 years old both stroke and MI were significantly decreased </li></ul>
    48. 51. Aspirin Evidence: Primary Prevention BDT, 1988 Combined PPP, 2001 HOT, 1998 TPT, 1998 PHS, 1989 RR of MI in Men 1.0 2.0 5.0 0.5 0.2 RR = 0.68 (0.54-0.86) P=0.001 1.0 2.0 5.0 0.5 0.2 RR = 1.13 (0.96-1.33) P=0.15 HOT, 1998 Combined WHS, 2005 PPP, 2001 1.0 2.0 5.0 0.5 0.2 Aspirin Better Placebo Better RR = 0.99 (0.83-1.19) P=0.95 1.0 2.0 5.0 0.5 0.2 Aspirin Better Placebo Better RR = 0.81 (0.69-0.96) P=0.01 RR of CVA in Men RR of MI in Women RR of CVA in Women Ridker P et al. NEJM 2005;352:1293-304 CVA=Cerebrovascular accident, MI=Myocardial infarction, RR=Relative risk
    49. 52. <ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors </li></ul><ul><li>Preventive Medications </li></ul><ul><ul><li>Statins reduce CHD in both men and women, however the NNT in women is greater </li></ul></ul><ul><ul><li>ASA (50 mg/d) reduces the risk of stroke, but not MI in low risk women under the age of 65. For men, low dose ASA has shown the opposite </li></ul></ul><ul><li>Lifestyle Interventions </li></ul>How we’ve changed our thinking about Primary Prevention in Women
    50. 53. Women’s Health Initiative Study Reducing Total Fat Intake <ul><li>Study the effect of low-fat, high fruit, vegetable, and grain diet on breast cancer, colorectal cancer and heart disease in postmenopausal women </li></ul><ul><li>Diet NOT designed for weight loss </li></ul><ul><li>Women followed 8.1 years </li></ul><ul><li>48,000 postmenopausal woman </li></ul><ul><ul><li>No intervention – 60% of participants </li></ul></ul><ul><ul><li>Intervention (dietary change) – 40% of participants </li></ul></ul>
    51. 54. WHI – Heart Disease: RESULTS <ul><li>No reduction in risk of MI or CHD death </li></ul><ul><li>Small but significant improvements in risk factors including: </li></ul><ul><ul><li>Body weight </li></ul></ul><ul><ul><li>LDL </li></ul></ul><ul><ul><li>Diastolic blood pressure </li></ul></ul><ul><ul><li>Factor VII C (a blood clotting factor) </li></ul></ul>
    52. 55. WHI : What went wrong? <ul><li>Dietary pattern reduced ALL types of fat </li></ul><ul><li>Diet designed for heart disease would focus on reducing saturated and trans fat </li></ul><ul><li>Relied on food frequency questionnaires which rely heavily on memory* </li></ul><ul><li>Participants started the study late in life* </li></ul>
    53. 56. Trans Fatty Acids and CHD Risk in Women Sun et. al. Circulation 2007: 115 <ul><li>Blood samples from 32,836 NHS subjects </li></ul><ul><li>6 yr F/U 166 CHD events </li></ul><ul><li>Nested case/control </li></ul><ul><li>RBC trans fatty acid content divided into quartiles </li></ul><ul><li>Multivariable relative risks </li></ul><ul><ul><li>Q1 vs. Q2 = 1.6 </li></ul></ul><ul><ul><li>Q1 vs. Q3 = 1.6 </li></ul></ul><ul><ul><li>Q1 vs. Q4 = 3.3 </li></ul></ul>
    54. 57. <ul><li>Hormone Therapy </li></ul><ul><li>Risk Factors </li></ul><ul><li>Preventive Medications </li></ul><ul><li>Lifestyle Interventions </li></ul><ul><ul><li>Diets that lower only total fat intake, and are started later in life may not decrease CHD </li></ul></ul><ul><ul><li>Trans fat intake is strongly associated with increased CHD in women </li></ul></ul>How we’ve changed our thinking about Primary Prevention in Women

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