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Coronary Heart Disease in Women

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. Statistics. Heart Disease and Stroke First and third leading causes of death in US

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Coronary Heart Disease in Women

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  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. Statistics • Heart Disease and Stroke • First and third leading causes of death in US • Accounts for more than 40% of all deaths • About 95,000 Americans die of heart disease or stroke each year • Amounts to one death every 33 seconds • Heart Disease is the leading cause of disability among working adults

  3. 0 Cardiovascular Disease Mortality Trends for Males and Females United States: 1979-2003 Source: CDC/NCHS.

  4. Hospital Discharges for Heart Failure by Sex - United States: 1979-2003 700 600 500 Discharges in Thousands 400 300 200 100 0 79 80 85 90 95 00 03 Years Male Female Source: National Hospital Discharge Survey, CDC/NCHS and NHLBI.

  5. Prevalence of cardiovascular diseases in adults by age and sex (NHANES: 1999-2004). Source: NCHS and NHLBI. These data include coronary heart disease, heart failure, stroke and hypertension.

  6. Incidence of cardiovascular disease by age and sex

  7. Annual rate of first heart attacks by age, sex and race (ARIC: 1987-2000). Source: NHLBI’s ARIC surveillance study, 1987-2000.

  8. Hospital discharges for heart failure by sex (United States: 1979-2004). Source: NHDS, NCHS and NHLBI. Note: Hospital discharges include people discharged alive, dead and status unknown..

  9. Women and Heart Disease

  10. Heart Disease is the #1 Killer of Women • Coronary heart disease is the single leading cause of death and a significant cause of morbidity among American women. • In 1997 CHD claimed the lives of 502,938 women (men had less deaths) • Since 1984, CVD has killed more American women than men each year.

  11. “Breast Cancer is the REAL issue!” • Who cares about heart disease doc…I am more concerned about: BREAST CANCER and lung cancer!” • In a recent survey, 75% of women identified cancer as their leading cause of death…

  12. In perspective: • 1 in 2 women will die of heart disease. • 1 in 25 women will die of breast cancer.

  13. CHD Mortality in Younger Women Women under 65 suffer the highest relative sex-specific CHD mortality

  14. Coronary Heart Disease in Women • Presentation and differences from men • 2/3 of women who die suddenly have no previously recognized symptoms. • Women are more prone to non-cardiac chest pain….. • 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 Source: Milner Am J Cardiol 1999;84:396

  15. Perception 67% knowledgeable that chest pain can be heart disease <10% knowledgeable that SOB, nausea, indigestion can be heart disease Reality chest pain is the presenting symptom in <50% of women Almost half of MIs in women present with SOB, nausea, indigestion, fatigue and shoulder pain Nationally: The Problem – AWARENESS

  16. Causes of Confusion: • Women may experience more dizziness, nausea, indigestion, and fatigue than men. • Women are more likely to have neck, arms, back and shoulder pain.

  17. Women and Heart Disease Risk Factors

  18. Trends in total cholesterol among adolescents ages 12-17 by race and sex (NHES: 1966-70; NHANES: 1971-74 and 1988-94). Source: NCHS and NHLBI.

  19. Non-modifiable Risk Factors • Age > 55 • CAD rates are 2-3x’s higher in postmenopausal women • Family history • CHD in primary 1st degree relative male<55 or female<65

  20. The #1 Preventable Risk- Smoking • A. 50% of heart attacks among women are due to smoking. Smokers tend to have their first heart attack 10 years earlier than nonsmokers. • B. If you smoke, you are 4-6x’s more likely to suffer a heart attack and increase your risk of a stroke. • C. Women who smoke and take OCP’s increase their risk of heart disease 30x’s.

  21. SMOKING: • Stop!!!!! (avg. attempt = 8 times) • Women who have other smokers in their household have a 2.5 X's greater likelihood of relapse. Circulation 2002:106 • Smoking cessation was associated with a 36% reduction in mortality among patients with CHD. JAMA 2003:290

  22. Hypertension • 65% of all hypertension remains either undetected or inadequately treated. • People who are normotensive at 55 have a 90% lifetime risk of developing HTN. • Prevalence increases with age and women live longer- hypertension is more common in females. • HTN is more common with OCP and obesity.

  23. Women and HTN—JNC VII • The relationship bet. BP and CV events is continuous, consistent and independent of other risk factors. • The higher the BP the greater the chance of MI, CHF, stroke, and kidney disease. • Can try to achieve good BP through lifestyle changes.

  24. Risk Factors: Diabetes • Diabetes increases the risk of CHD 3-7 X in women versus 2-3 X in men. • Diabetic women who smoke have a 84% higher risk of developing stroke than nonsmokers. • 2 of 3 people with diabetes die from CHD or stroke.

  25. Cholesterol • More than 55 million women (45million men) have TC>200. • Check cholesterol at least once q 5yr’s starting at age 20. • 36 Million people in the US should be taking a statin according to guidelines, but only 11 million are.

  26. Lifestyle Modification for HTN

  27. Cholesterol • Women at high risk should be considered for statin therapy regardless of cholesterol-LDL levels. • 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

  28. How we’ve changed our thinking about Primary Prevention in Women • Hormone Therapy • Risk Factors • Preventive Medications • Lifestyle Interventions

  29. HERS: Combined HT Does Not Decrease All-Cause Mortality 15 Estrogen-Progestin Placebo 10 Incidence (%) 5 0 0(2763) 1(2720) 2(2666) 3(2595) 4(1590) 5(130) Follow-up, y (no. at risk) Hulley S, et al. JAMA. 1998;280:605–613.

  30. 0.03 0.03 0.03 0.02 0.02 0.02 0.01 0.01 0.01 0 0 0 Estrogen + Progestin and Disease in WHI* Coronary Heart Disease HR = 1.29 95% nCI. 1.02–1.63 95% aCI. 0.85–1.97 Stroke HR = 1.41 95% nCI. 1.07–1.85 95% aCI. 0.86–2.31 Cumulative Hazard Pulmonary Embolism HR = 2.13 95% nCI. 1.39–3.25 95% aCI. 0.99–4.56 Invasive Breast Cancer HR = 1.26 95% nCI. 1.00–1.59 95% aCI. 0.83–1.92 Cumulative Hazard Estrogen + Progestin Colorectal Cancer HR = 0.63 95% nCI. 0.43–0.92 95% aCI. 0.32–1.24 Hip Fracture HR = 0.66 95% nCI. 0.45–0.98 95% aCI. 0.33–1.33 Cumulative Hazard Placebo 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Time (y) Time (y)

  31. WHI E+P Trial Findings, July 2002 (avg 5.2 y) Risks Benefits 105% Increase Dementia Fracture Reduction (Hip 23%) 24% IncreaseCHD 39% Reduction Colorectal Cancer 31% Increase Stroke 111% Increase Pulmonary Emboli 24% Increase Breast Cancer STOPPED Early, Clear Harm Stopped 3.3 yrs early Also: DVTs JAMA. 2002;288:321-333

  32. Summary of WHI Estrogen-Alone Results Event Relative Hazard 95% CI Inv. Breast Cancer 0.77 0.59-1.01 CHD 0.91 0.75-1.12 Hip Fracture 0.61 0.41-0.91* All Fractures 0.70 0.63-0.70* Colorectal Cancer 1.08 0.75-1.15 _____________________________________________ *p<.05 JAMA, 4/14/04

  33. WHI E Alone Trial Findings, 2004 (avg 6.8 y) Neutral forCHD Neutral for breast cancer Risks 49% Increase Dementia Benefits 39% Increase Stroke Fracture Reduction (Hip 39%) 34% Increase Pulmonary Emboli STOPPED Early, suggestion of harm Stopped 1.7 yrs early Also: DVTs JAMA 2004;291:2947-58

  34. Estrogen in the early menopausal years • Analysis of 24,317 women 50-79 years old in WHI • whose age at menopause could be defined • stratified into 3 groups: 50-59/ 60-60 /70-79 y.o. • CHD, stroke & mortality rates analyzed • Stroke was increased in all women, regardless of age at menopause or E vs. E + P • CHD was decreased in women who took E alone vs. E + P (0.95 vs. 1.23 p=0.02) • In hormone users • HR for CHD if < 10 years from menopause = 0.76 • HR for CHD if 10-20 from menopause = 1.10 • HR for CHD if >20 years from menopause = 1.28 Rossouw, J. E. et al. JAMA 2007;297:1465-1477.

  35. Current research centers around the question: Does estrogen mean different things in different vessels?

  36. How we’ve changed our thinking • Hormone Therapy • WHI - Combined hormone therapy increases cardiovascular risk overall * (but may be safe/?beneficial in the early menopausal years) • WHI - Estrogen only therapy is neutral on CHD • Risk Factors • Preventive Medications • Lifestyle Interventions

  37. 40 35 30 25 20 15 10 5 0 NHANES III: Age-Adjusted Prevalence of ≥3 Risk Factors for the Metabolic Syndrome* Men 35.6 Women 28.3 25.7 24.8 22.8 Prevalence( %) 16.4 African American White Mexican American *Criteria based on ATP III; diabetics were included in diagnosis; overall unadjusted prevalence 21.8%. Ford ES et al. JAMA. 2002;287:356-359.

  38. Elevated Triglycerides Increase CHD Risk Framingham Heart Study Relative Risk for CHD Women Men For every increase in serum TG level of 89 mg/dL, risk of CHD increases 30% in men and 69% in women13.14 Meta-Analysis of 17 Prospective Studies

  39. CVD Events in Patients With Diabetes: Framingham Heart Study 30-Year Follow-Up 12 Men * 10 * Women 8 * 6 Relative Risk Ratio‡ * * 4 * * * † 2 0 Total CVD CHD Cardiac Failure Intermittent Claudication Stroke *.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.

  40. Gender Hazard ratio 95% CI p Men 0.9 0.5-1.7 NS Women 2.2 1.4-3.5 0.0001 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.

  41. How we’ve changed our thinking about Primary Prevention in Women • Hormone Therapy • Risk Factors • Triglycerides, diabetes, and the metabolic syndrome are greater risks for women as compared to men • Preventive Medications • Lifestyle Interventions

  42. Meta-analysis from CholesterolClinical Trialists (CCT) Collaboration Events Groups Treatment Control Heterogeneity/trend test 45,002 45,054 RR Post MI Other CHD None 1681 (11.7%) 568 (8.7%) 1088 (4.5%) 2207 (15.4%) 744 (11.4%) 1469 (6.1%) 0.78 (0.74-0.84) 0.77 (0.68-0.87) 0.72 (0.66-0.80) P=0.2 Sex Male Female 2686 (7.8%) 651 (6.1%) 3630 (10.6%) 790 (7.3%) 0.76 (0.72-0.80) 0.82 (0.73-0.93) P=0.1 0.5 1.0 1.5 Treatment better Control better Cholesterol Clinical Trialists Collaboration. Lancet. 2005;366:1267.

  43. Aspirin Evidence: Primary Prevention in Men Physicians’ Health Study (PHS) 22,071 men randomized to aspirin (325mg QOD) followed for 5 years Aspirin significantly reduces the risk of MI in men CI=Confidence interval, MI=Myocardial infarction Physicians’ Health Study Research Group. NEJM 1989;321:129-35

  44. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial 39,876 initially healthy† women, aged 45 yrs Randomized, blinded, factorial Placebo n=19,942 Low-Dose Aspirin 100 mg on alternate days n=19,934 • End points (mean, 10.1 yrs): • Combined end point of nonfatal MI, nonfatal stroke, or total cardiovascular death • Incidence of total malignant neoplasms of epithelial cell origin † 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. Ridker PM. Presented at: 54th Annual Scientific Session of the American Collegeof Cardiology; March 7, 2005; Orlando, Fla. Ridker PM, et al. N Engl J Med. 2005;352.

  45. Aspirin : Primary Prevention in Women Womens’ Health Study (WHS) 39,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years Aspirin Placebo Cumulative Incidence of MI P=0.83 Years Aspirin does not reduce the risk of MI in low risk women MI=Myocardial infarction Ridker P et al. NEJM 2005;352:1293-304

  46. Conclusions • 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

  47. Aspirin Evidence: Primary Prevention BDT, 1988 RR of MI in Men RR of CVA in Men PHS, 1989 TPT, 1998 HOT, 1998 PPP, 2001 RR = 0.68 (0.54-0.86)P=0.001 RR = 1.13 (0.96-1.33)P=0.15 Combined 0.2 0.5 1.0 2.0 5.0 0.2 0.5 1.0 2.0 5.0 RR of MI in Women RR of CVA in Women HOT, 1998 PPP, 2001 WHS, 2005 RR = 0.99 (0.83-1.19)P=0.95 RR = 0.81 (0.69-0.96)P=0.01 Combined 0.2 0.5 1.0 2.0 5.0 0.2 0.5 1.0 2.0 5.0 Aspirin Better Placebo Better Aspirin Better Placebo Better CVA=Cerebrovascular accident, MI=Myocardial infarction, RR=Relative risk Ridker P et al. NEJM 2005;352:1293-304

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