Women and Heart Disease - Dr. Eastwood


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  • 1979 was a landmark year, this is the first year when the CDC actually reported heart disease deaths according to gender.
  • Because women lag 10-20 years behind men and are less likely to receive efficient care upon presentation, it is likely that they will spend their later years with a decreased QOL.
  • The significance of cardiovascular disease (CVD) as a health concern is illustrated by examining mortality rates per 100,000 women aged 45 years and older. The number of women who die each year from CVD is higher than the number who die from stroke or from lung, breast, colon, or endometrial cancer in any age group.
  • Dr. Lori Mosca, lead author on 2007 guidelines found that in 2006 a woman’s overall awareness of heart disease as the leading cause of death was 57%, although a major gain from prior years awareness among black and hispanic women was lower at 31% and 29% versus 68% for white women. Awareness is linked to action so this presents a problem.
  • In 2007 the NHLBI reported that 17,000 fewer American women died from heart disease in 2003-2004. According to their Heart truth campaign the number of women who die from heart disease has shifted from 1 in 3 to 1 in 4. Every year organizations such as American Heart Association focus on efforts to improve awareness of heart disease among women. AHA;s Go Red for women national campaign encurages women to know their numbers…they have a National Wear Red Day and introduce websire tools and charts listing the major risk factors and corresponding goals. There have been improvements in risk factors such as HTN and cigarette smoking owever this gain is overshadowed by the growing trends of obesity.
  • Women are less likely to be counseled on cardiovascular disease risk behaviors compared with men in outpatient office visits.
  • - Among hypercholesterolemic subjects, women were less likely than their male counterparts to be aware. However, once aware their was no difference in treatment or control. 1 - Additionally, baseline hypercholesterolemia was more prevalent in women than in men [2509 (29%) versus 1693 (24%), p <0.001)]. 1 1 Nieto, et al. Arch Int Med. Vol 155,Apr.10,1995.
  • Utilization of lipid-lowering medications at discharge in patients with AMI: National Registry of Myocardial Infarction (NRMI) 3 In this study, the use of lipid-lowering therapy at the time of discharge after acute myocardial infarction (AMI) was assessed in 138,001 patients enrolled from 1470 National Registry of Myocardial Infarction (NRMI) 3 hospitals from July 1998 to June 1999. This study demonstrates that in all age groups and in both men and women, only a small proportion of AMI patients were started on lipid-lowering therapy. Overall, only 31.9% of these high-risk patients were receiving lipid-lowering medications. Reference: Fonarow GC, French WJ, Parsons LS, Sun H, Malmgren JA, for the National Registry of Myocardial Infarction 3 Participants. Use of lipid-lowering medications at discharge in patients with acute myocardial infarction: data from the National Registry of Myocardial Infarction 3. Circulation 2001;103:38-44.
  • Heart Disease is preventable if awareness is raised. Look at Breast Cancer. Because of the excellent job that has been done to raise awareness numbers are dropping. There is nearly one death per minute. The AHA and 11 other organizations came together and developed comrehensive guidelines for heart disease prevention in women. Over 7000 scientific articles were used. The goal was to help women achieve a heart healthy life and reduce their chances of heart attack or stroke. Awareness, knowledge and action in saying “ goodbye” (ALOHA ) to the no.1 killer of women.
  • The following are Class II recommendations: 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 Consider screening women with CHD for depression and refer/treat where indicated The following are Class II recommendations: 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 Consider screening women with CHD for depression and refer/treat where indicated Lifestyle and pharmacotherapy should be used as indicated in women with diabetes to achieve an HbA1C <7% Insulin, metformin, TZDs, and DPP-4 inhibitors are important classes of drugs that aid in diabetes control With regards to weight loss: 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. Encourage optimal BP of <120/80 mmHg through lifestyle approaches 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
  • This slide shows the results of a sex-specific meta-analysis of data from 6 primary prevention trials: the British Doctors' Trial (BDT), the Physicians' Health Study (PHS), the Thrombosis Prevention Trial (TPT), the Hypertension Optimal Treatment (HOT) study, the Primary Prevention Project (PPP), and the current Women's Health Study (WHS). This slide suggests that for primary prevention in men, aspirin is beneficial in preventing myocardial infarction (MI) but not stroke, and in women, aspirin is beneficial in preventing stroke but not MI.
  • This slide shows the individual results of the secondary-prevention trials for the end point of CHD events in 8272 women with heart disease. As seen here, all 4 studies found a significant reduction in risk associated with lipid-lowering in women with heart disease. The summary risk reduction (RR) for these trials was .80 (95% CI, 0.71-0.91), indicating a 20% reduction in risk with lipid lowering in secondary prevention. 63 63. Walsh JME, Pignone M. Drug treatment of hyperlipidemia in women. JAMA. 2004;291:2243-2252.
  • 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.
  • 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 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.
  • 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.
  • 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 .
  • Diabetes washes out the protective effects of estrogen in young women.
  • 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.
  • 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.
  • Pooled data from 30 rndomized controlled trials of HRT vs. placebo or no treatment, each longer than 6 months and reporting at least 1 death. Together the pooled trials including both the WHI estrogen-plus progestin trial and HERS provided data on 26,708 subjects. When the results for all ages were combined, there was no signif. Diff in total mortality between women in the treatment and control groups. Howeve, when trials were divided into those w a mean age of<60 and >60 at baseline, there was a 40% reduction in mortality for the younger age group. There was no significant increase or decrease n mortality seen in the older age group. For all ages
  • Women and Heart Disease - Dr. Eastwood

    1. 1. Heart Disease in Women: A Call to Action <ul><li>Jo-Ann Eastwood, PhD, CCNS, ACNP-BC </li></ul><ul><li>Assistant Professor </li></ul><ul><li>UCLA School of Nursing </li></ul><ul><li>Nurse Researcher </li></ul><ul><li>Woman’s Heart Program </li></ul><ul><li>Cedars Sinai Medical Center </li></ul>
    2. 2. Heart Disease The leading killer of women at all ages
    3. 3. 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.
    4. 4. So how long have we known that women are just not small men???
    5. 5. Cardiovascular disease mortality trends for males and females ( United States: 1979-2004). Source: NCHS and NHLBI. 0
    6. 6. (United States:2004) * - Not a true underlying cause. Source: NCHS and NHLBI. Percentage breakdown of deaths from cardiovascular diseases
    7. 7. CVD runs a very different course in women <ul><li>Women develop 10-20 years later than men </li></ul><ul><li>If present at younger age – more malign clinical course </li></ul><ul><li>DM and HTN have relatively >role in women compared to men </li></ul><ul><li>Clinical manifestations of HF as well as Rx responses differ </li></ul>
    8. 8. And Most Importantly…. <ul><li>Despite technological and pharmaceutical advances there are little to no reductions in morbidity and mortality for women </li></ul><ul><li>Awareness, or the lack there of is a significant problem. </li></ul>
    9. 9. WOMEN’S HEALTHCARE COST GAP: CVD is the most costly and most preventable disease in women, yet we spend the leas t on screening and prevention Billions $60 Hoerger et al, J WH&Gender-Based Med 1999;8:1077 4% 3% 38% 18% We are missing important CVD treatment opportunities! $13 $2 $3
    10. 10. 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.
    11. 11. Mortality Rates in Women At Every Age, More Women Die From Heart Disease Than From Cancer National Center for Health Statistics. 1999:164-167. Coronary artery disease Stroke Lung cancer Breast cancer Colon cancer Endometrial cancer Age (years) Mortality Rate per 100,000 45 – 49 50 – 54 55 – 59 60 – 64 65 – 69 70 – 74 75 – 79 80 – 84 85+ 50% of women (1 in 2) will die from CVD compared with 4% (1 in 25) who will die from breast cancer 6500 4500 2500 1600 1200 800 400 0
    12. 12. 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.
    13. 13. Women and Heart Disease: Making an Impact <ul><li>􀂾 </li></ul><ul><li>AHA National Awareness Survey </li></ul><ul><li>􀁺 </li></ul><ul><li>1997– 30% aware heart disease is #1 killer </li></ul><ul><li>􀁺 </li></ul><ul><li>2000– 34% </li></ul><ul><li>􀁺 </li></ul><ul><li>2003– 46% </li></ul><ul><li>􀁺 </li></ul><ul><li>2008– 60% </li></ul><ul><li>􀂾 </li></ul><ul><li>Knowledge gap remains </li></ul><ul><li>– especially in women younger than 45, Hispanic, and African American women </li></ul><ul><li>􀂾 </li></ul><ul><li>“ Disconnect” remains – only 13% say heart disease is their own greatest health risk </li></ul>
    14. 14. Coronary Heart Disease Mortality Among Young Adults in the US: 1980 1980-2002 (Ford et al JACC,2007) <ul><li>􀂾 </li></ul><ul><li>Included women and men aged 35 and older using ICD-9 codes in US Census data </li></ul><ul><li>􀂾 </li></ul><ul><li>Mortality from CHD fell 52% in men and 49% in women </li></ul><ul><li>􀂾 </li></ul><ul><li>Improved mortality each decade from 1980s, 1990s until the 2000s </li></ul><ul><li>􀂾 </li></ul><ul><li>Age analysis demonstrates:􀁺 </li></ul><ul><li>Leveling off of mortality decline in men 35-54 yrs in the 2000s </li></ul><ul><li>􀁺 </li></ul><ul><li>Actual increase in mortality in women 35-54 yrs, and specifically among women 35-44 yrs (p<0.05) </li></ul><ul><li>Results are consistent with a UK study (O’Flahrty et al Heart 2007:10:1136. </li></ul><ul><li>Concomitant with increased use of thrombolysis, PCI, statins and anti-thrombotics (ASA), yet adverse nutrition, physical activity, obesity and smoking trends. </li></ul>
    15. 15. Definitions <ul><li>Primary Prevention: Modification of risk factors or prevention of their development in order to prevent or delay the onset of coronary heart disease (CHD) </li></ul><ul><li>Secondary Prevention: Initiation of therapy to reduce recurrent CHD events and decrease cardiac mortality in patients with established CHD </li></ul><ul><li>Primary-and-a-half Prevention*: As individuals with subclinical CHD are identified, the distinction between primary and secondary prevention becomes blurred </li></ul>*Celermajer DS. J Am Coll Cardiol. 2005;45:1994-1996.
    16. 16. ( United States: 2004). Source: NCHS and NHLBI. Age-adjusted death rates for CHD, stroke, lung and breast for white and black females
    17. 17. Cost-Efficacy of Treatment ( Cost-effective < $50,000) <ul><li>Mammography 1 </li></ul><ul><li>Age Group Cost/yr of life saved </li></ul><ul><li>50 to 69 $21,400 </li></ul><ul><li>40 to 49 $150,000 </li></ul><ul><li>Statin Lipid Lowering 2 </li></ul><ul><li>CVD Status Cost/yr of life saved </li></ul><ul><li>Yes $8,400 </li></ul><ul><li>No $50,000 </li></ul><ul><li> </li></ul>1 Salzmann & Kerlikowske, Ann Intern Med, 1997; 2 NCEP III, ATP 2002
    18. 18. Heart Disease Risk Differs Between Women and Men <ul><li>More women than men will have a second heart attack within 6 years after their first heart attack </li></ul><ul><li>Women with diabetes are 3 to 4 times more likely than men to develop heart disease </li></ul><ul><li>Diabetes doubles the risk of a second heart attack in women </li></ul>National Heart, Lung, and Blood Institute. The Healthy Heart Handbook for Women . 2003.
    19. 19. Racial and Ethnic Minority Women and Cardiovascular Disease <ul><li>African American women experience CVD at the highest rate in the United States </li></ul><ul><li>Data on racial and ethnic minorities may underestimate disease prevalence/mortality, especially in American Indians and Alaskan Natives </li></ul><ul><li>Racial and ethnic minority women have higher mortality rates at younger ages </li></ul><ul><li>Issues regarding access to information and access to care; cultural competence of providers </li></ul>Mosca L et al. Circulation . 2004;109:573-579. Epub 2004 Feb 4.
    20. 20. Counseling During Office Visits CDC. 1995 NAMCS. Morb Mortal Wkly Rep . 1998;47:91-95. % Men Women Physical activity Diet Weight reduction 0 10 20 30
    21. 21. Hypercholesterolemic Subjects by Sex: The Atherosclerosis Risk in Communities Study, 1987-1989. % Aware n = (1748/4202) % Treated n = (446/1664) % Controlled n = (155/446) Nieto, et al. Arch Int Med. Vol 155,Apr.10,1995.
    22. 22. Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI: National Registry of Myocardial Infarction (NRMI) 3 Fonarow GC et al. Circulation 2001;103:38-44. % Discharged on Lipid Therapy Male (n=83,806) P<0.0001 Female (n=54,195) Age (Years) P<0.0001 P<0.0001 P=NS P=NS <55 55–64 65–74 75–84 85+ 138,001 patients discharged from 1470 US hospitals, July 1998 to June 1999
    23. 23. Mosca L et al. Circulation . 2004;109:672-693.
    24. 24. 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
    25. 25. 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>
    26. 26. 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>
    27. 27. Priorities for Prevention in Practice According to Risk Assessment High-Risk Women (>20% Risk) Intermediate-Risk Women (10% to 20% Risk) Lower-Risk Women (10% Risk) Class I recommendations Smoking cessation Phys activity/card rehab Diet therapy Weight maint/reduct BP control Cholest control/Rx Aspirin therapy -Blocker therapy ACE inhibitor (ARBs) Mgmt/control of DM Smoking cessation Physical activity Heart-healthy diet Weight maint/reduct BP control Cholesterol control Smoking cessation Physical activity Heart-healthy diet Weight maint/reduct Treat individual heart risk factors as indicated Class IIa recommendation Treatment for depression Aspirin therapy Class IIb recommendations Omega 3 fatty-acid supplementation Folic acid supplementation Mosca, L “Heart Disease Prevention in Women” Circulation, 2004
    28. 28. 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
    29. 29. Essential Components of NCEP Therapeutic Lifestyle Change (TLC) <ul><ul><li>Decrease in saturated fats (<7% of total calories) and trans fatty acids 1 </li></ul></ul><ul><ul><li>Increased dietary and supplemental fiber 1 </li></ul></ul><ul><ul><ul><li>High-fiber breakfast cereals, supplements, and so forth </li></ul></ul></ul><ul><ul><li>Plant sterols and stanols (2 g/d) 1 </li></ul></ul><ul><ul><ul><li>Spreads, pills, added to yogurt or other foods, or combined with aspirin </li></ul></ul></ul><ul><ul><li>Soy protein 2 </li></ul></ul><ul><ul><li>Flavonoids (nuts) 3 </li></ul></ul><ul><ul><li>Weight loss 1 </li></ul></ul><ul><ul><li>Exercise 1 </li></ul></ul>1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285(19):2486-2497. • 2. Sacks FM, et al; American Heart Association Nutrition Committee. Circulation . 2006;113(7):1034-1044. • 3. Kelly JH Jr and Sabaté J. Br J Nutr . 2006;96(suppl 2):S61-S67.
    30. 30. Aspirin in Primary Prevention: Effective Gender Differences Ridker, P. et al., N Engl J Med 2005; 352:1293-204. 1.0 5.0 0.5 0.2 0.2 0.5 1.0 2.0 5.0 BDT, 1988 Combined PPP, 2001 HOT, 1998 TPT, 1998 PHS, 1989 RR of MI Among Men 2.0 RR = 0.68 (0.54 – 0.86) P = .001 RR of Stroke Among Men RR = 1.13 (0.96 – 1.33) P = .15 1.0 0.2 2.0 5.0 0.5 HOT, 1998 Combined WHS, 2005 PPP, 2001 RR of MI Among Women Aspirin Better Placebo Better RR = 0.99 (0.83 – 1.19) P = .95 2.0 Aspirin Better Placebo Better 1.0 RR of Stroke Among Women 5.0 0.5 0.2 RR = 0.81 (0.69 – 0.96) P = .01
    31. 31. CHD Events: Results of Secondary Prevention Studies in Women P value for heterogeneity=.35 Walsh et al. JAMA . 2004;291:2243-2252. Placebo No. Events/Women Intervention No. Events/Wome n RR (95% CI) 4S 91/420 60/407 0.68 (0.51-0.91) CARE 80/290 46/286 0.60 (0.37-0.97) LIPID 104/760 90/756 0.87 (0.67-1.13) HPS 282/1638 237/1628 0.85 (0.72-0.99) Total and summary 557/3108 433/3077 0.80 (0.71-0.91)
    32. 32. Blood Pressure Regulation in Women <ul><li>3 of every 4 women with high blood pressure know they have it </li></ul><ul><li>Fewer than 1 in 3 are controlling it </li></ul><ul><li>All women must take steps to control their high blood pressure </li></ul>NIH Web site. Your guide to lowering high blood pressure: issues for women. Available at: http://www.nhlbi.nih.gov/hbp/issues/issues.htm.
    33. 33. AHA Guidelines for CVD Prevention in Women: Blood Pressure <ul><li>Encourage an optimal blood pressure of <120/80 mm Hg through lifestyle approaches (Class I, Level B) </li></ul><ul><li>Pharmacotherapy when BP is </li></ul><ul><ul><li> 140/90 mm Hg </li></ul></ul><ul><li>Get BP even lower when </li></ul><ul><ul><li>Target-organ damage </li></ul></ul><ul><ul><li>Diabetes </li></ul></ul><ul><ul><li>(Class I, Level A) </li></ul></ul>Mosca L et al. J Am Coll Cardiol . 2004;43:900-921.
    34. 34. Additional Risk of CAD Events in Later Life <ul><li>Development of gestational diabetes </li></ul><ul><li>Development of pregnancy-related HTN </li></ul><ul><li>More recent data on preeclampsia and eclampsia </li></ul><ul><li>Clustering of risk factors as she ages should institute therapeutic lifestyle changes now </li></ul>
    35. 35. Women Experience Menopause….. <ul><li>Changes with Menopause </li></ul><ul><li>Lipids </li></ul><ul><li>Total-Cholesterol  </li></ul><ul><li>HDL-Cholesterol  </li></ul><ul><li>Prevalence Differences </li></ul><ul><li>Hypertension  </li></ul><ul><li>Metabolic Syndrome  </li></ul><ul><li>Risk Factor, Disease, or Outcome Risk </li></ul><ul><li>Triglycerides  Diabetes Mellitus  </li></ul><ul><li>Obesity (BMI > 30)***  </li></ul><ul><ul><ul><ul><li>Waist Circumference >35”  </li></ul></ul></ul></ul><ul><ul><li>*** Obesity ~25% of women - BMI > 30, Less leisure-time physical activity - Greater functional decline - </li></ul></ul>Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594
    36. 36. <ul><ul><li>75% of women experience vasomotor symptoms </li></ul></ul><ul><ul><li>during the transition to menopause </li></ul></ul>
    37. 37. 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>
    38. 39. 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?
    39. 40. Currently a Population at Risk <ul><li>Younger people are caught up in the obesity / diabetes epidemic </li></ul><ul><li>Need to impress: diet, smoking cessation, exercise, weight management </li></ul><ul><li>Frustration in treating women: No one test such as a mammogram to say Yes you have it………or you don’t </li></ul>
    40. 41. 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>
    41. 43. 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)
    42. 46. 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
    43. 47. 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.
    44. 48. The apple but not the pear shape is a health risk for women - which are you? Abdominal Obesity and gender differences
    45. 49. 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>
    46. 50. 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>
    47. 51. 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>
    48. 52. 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) Vascular Event Major coronary 1063 1047 Any stroke 511 518 Revascularization 1058 1086 Any of the above 2306 (22.5%) 2312 (22.5%) 0.4 0.6 0.8 1.0 1.2 1.4
    49. 53. 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>Meta analysis 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>
    50. 54. 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. 55. 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.
    52. 56. 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
    53. 57. 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>
    54. 59. 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)
    55. 60. Significant Coronary Artery Calcium (Score >400)
    56. 61. Risk of Total Mortality by Calcium Category in 10,377 Asymptomatic Individuals Shaw LJ et al., Radiology 2003; 228: 826-33
    57. 62. No insurance policy <ul><li>People get a false sense of security with 0-low CA scores </li></ul><ul><li>Those without coronary calcium can have events </li></ul>
    58. 64. Looking Forward: Assessing Disease <ul><li>A good risk assessment is key </li></ul><ul><li>Traditional diagnostic testing is not always optimum in women </li></ul><ul><li>Many women have more inward remodeling of the arteries </li></ul><ul><li>Men have more “lumpy bumpy” disease </li></ul>
    59. 65. Symptoms in Women with MI <ul><li>Chest pain can present as pressure or tightness but can also; </li></ul><ul><ul><li>Back pain </li></ul></ul><ul><ul><li>Abdominal pain </li></ul></ul><ul><ul><li>Jaw pain </li></ul></ul><ul><li>Other symptoms; </li></ul><ul><ul><li>Dyspnea </li></ul></ul><ul><ul><li>Nausea </li></ul></ul><ul><ul><li>Vomiting </li></ul></ul><ul><ul><li>Sweating </li></ul></ul><ul><ul><li>Excessive fatigue (prodromal symptoms up to a month prior to event) </li></ul></ul><ul><ul><li>McSweeney J 1999, 2002 </li></ul></ul>Half of women with MI have no prior chest pain symptoms Evaluate all symptoms above The waist for cardiac etiology FIRST!
    60. 66. Women have smaller coronary arteries <ul><li>After correcting for body surface area, womens’ arteries are smaller </li></ul><ul><li>This can seriously affect symptoms from anything that reduces diameter </li></ul><ul><ul><li>Stenosis </li></ul></ul><ul><ul><li>Endothelial dysfunction </li></ul></ul>Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594 Endo- thelium Smaller arteries
    61. 67. Plaque Erosion and Outward (Positive) Remodeling <ul><li>Plaque erosion and thrombus formation 2x likely in women (men have more plaque rupture) </li></ul><ul><li>Outward (positive) remodeling- atherosclerotic lesion protrudes outward than impinging on the lumen </li></ul>Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594 Thrombus Formation Lumen Plaque erosion
    62. 68. Women suffer more plaque erosions (above) compared to plaque explosions in men (below), leading to more acute coronary syndromes (unstable angina) and non-Q MI in women, making diagnosis more difficult and leading to delays in treatment. Gender Differences in Atherosclerosis NEJM 1999
    63. 70. NIH-NHLBI-sponsored Women’s Ischemia Syndrome Evaluation WISE <ul><li>About 50% of women sent home with “normal coronaries” continue to experience disabling symptoms </li></ul><ul><li>Possibly d/t coronary microvascular or macrovascular endothelial dysfunction </li></ul><ul><li>673/936 enrolled in WISE had PChP- </li></ul><ul><li>PChP-w no obstructive disease is not a benign condition </li></ul><ul><ul><li>2x the number of CV events (MIs, strokes,CHF and CV deaths) than those w/o PChP. </li></ul></ul><ul><ul><li>Johnson,D, etal EurHeart Journal 2006 </li></ul></ul>
    64. 71. Assessing Ischemic Disease <ul><li>Stress EKG may be less useful in looking for ischemia </li></ul><ul><ul><li>Guidelines still support for women with normal resting 12 lead EKG </li></ul></ul><ul><li>Decreased functional capacity may predict poor outcomes </li></ul><ul><ul><li>WISE showed that women who could not achieve 4.7 METS of work had a risk of death or nonfatal MI 3.7x higher that others with better functional capacity </li></ul></ul><ul><li>Stress ECHO and SPECT are good options in women </li></ul>
    65. 72. And What about HRT Confusion ????
    66. 73. 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
    67. 74. 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
    68. 75. 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) </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>
    69. 76. Does Hormone Replacement Therapy Prevent Heart Disease? <ul><li>Meta-Analysis of randomized trials show a 40% reduction in total mortality w HRT vs placebo or no treatment but only when women were <60 yrs @ baseline. </li></ul><ul><li>July 2004 Journal of General Internal Medicine </li></ul><ul><li>Nurses’ Health Study showed those on estrogen/progestin to have approximately a 60% lower risk of heart disease events </li></ul>
    70. 77. 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 embolism 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 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>
    71. 79. Women Making a Change