Women s Heart Disease: Yelena Rosenberg MD Skagit Regional Clinics Cardiology

Transcription

1 Women s Heart Disease: Yelena Rosenberg MD Skagit Regional Clinics Cardiology

2 Talk Summary Role of gender in afib Randomized trial of low-dose aspirin in women ASA in stroke prevention and CAD Role of gender in supplement utilization, in particular role of calcium in MI

3 Clinical Question 1 A 76 year old woman comes to your clinic with a new diagnosis of paroxysmal atrial fibrillation; she has severe uncontrolled hypertension (SBP currently 160 mm hg) associated with hypertensive heart disease. Patient has normal LV systolic function; no diabetes or prior stroke. No falls, anemia or gastrointestinal bleeding. Do you recommend anticoagulation medication for stroke prevention for this patient? YES NO

4 Predictive Capacity of Risk Stratification Calculators Stroke calculators which incorporate gender perform better in terms of predicting risk of stroke Women suffering from AF show greater adjusted odds ratio for death and stroke compared to men

5 Female patients have greater mortality risk as a result of afib diagnosis Men Women Death rate among afib patients 61% 58% Death rate among those without afib 30% 21% Odds Ratio (adjusted for age, CAD, etc) Benjamin EJ, Wolf PA, D Agostino, Silbershatz H, Kannel W, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham heart Study. Circulation. 1998; 98(10):

6 Females have greater stroke risk than men as a result of afib diagnosis Wagstaff AJ, Overard TG, Lip GY, Lane DA. Is female sex a risk factor for stroke and thromboembolism in patients with atrial fibrillation? A systematic review and meta-analysis. QJM. 2014; 107(12);

7 What is our patient s annual stroke risk (if she choses to forego anticoagulation)? Risk Scheme Gender Included Incorporated Characteristics CHADS2 NO Chf, hypertension, age>75, diabetes, stroke AFI NO HTN, Age, Diabetes, Prior stroke/tia Risk Score 2 4% Stroke risk year 1 8.1% Framingham YES Age, LVH on EKG % CHADS2Vasc (aka Birmingham) YES CHF, HTN, age>75,dm, Stroke, MI/PAD/Aortic plaque, Female gender, Age65-75 yo 4 2.3%

8 Ishemic Stroke Risk Stratification in Afib: AFI calculator Age Group Hypertension Diabetes Mellitus < >75 Prior stroke or TIA No risk factors 1% No risk factors 4.3% No risk factors 3.5% HTN or DM or stroke 4.9% HTN or DM or stroke 5.7% HTN or DM or stroke 8.1% No authors listed. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: Analyses of pooled data from five randomized controlled trials. Arch Intern Med. 1994:154(13):

9 Risk Stratification in Afib: CHADS2 calculator CHF (recent) Hypertension Age at least 74 years Diabetes Mellitus Prior stroke or TIA (add 2 points) Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial fibrillation. JAMA. 2001;285(22):

10 Risk Stratification in Afib: Framingham calculator Wang TJ, Massaro JM, Levy D, Vasan, RS, Wolf PA, D Agostino RB, Larson MG, Kannel WB, Benjamin EJ. A Risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290(8):

11 Risk Stratification in Afib: CHADS2Vasc calculator CHF Hypertension Age >75 (2 points) Diabetes Stroke (2 points) Vascular Disease Age Female Gender Wang TJ, Massaro JM, Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-based Approach: The Auro heart Survey on Atrial Fibrillation. Chest 2010; 137;

12 Risk Stratification in Afib: Performance Characteristics Risk Scheme C-statistic In original CHADS2vasc paper CHADS C-statistic in big Danish Cohort AFI Framingham CHADS2Vasc Olesen JB, Lip GY, Hansen ML, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ. 2011; 342:d124

13 Clinical Question 2: HRT and stroke in afib patients You spoke with your patient, and discussed her multiple risk factors for stroke, including her advanced age, hypertension and female gender. You recommend oral anticoagulation. She refuses warfarin and any other oral anticoagulation medication. She is willing to take Aspirin. Upon reviewing her medication list you notice that she is on estrogen/progesterone hormone replacement therapy (HRT). What do you tell her regarding HRT and risk of stroke in afib? Stop HRT! Studies support increased risk of stroke in patients with afib on HRT Keep HRT going. Studies do NOT support the hypothesis that HRT increases stroke risk in afib patients

14 HRT in patients with AFIB: AFFIRM experience 376 on HRT 1594 women 4060 patients 1218 NO HRT 2466 men AFFIRM HRT No HRT MACE 56 (14%) 270 (22%) No MACE Total HRT cohort had lower risk of MACE (χ 0.002) However, that does not mean that HRT is protective Use of HRT associated with healthier, more educated and more compliant patients In particular, patients on HRT had greater therapeutic time than non- HRT patients Apostolakis S, Sullivan RM, Alshansky B, Lip GY. Hormone replacement therapy and adverse outcomes in women with atrial fibrillation: an analysis from the atrial fibrillation follow-up investigation of rhythm management trial. Stroke. 2014; 45(10):

15 HRT in patients with AFIB: SPAF III experience 1182 AFFIRM HRT No HRT Stroke 9 (10%) 6 (3%) No Stroke Total on HRT 274 women 184 NO HRT 908 men HRT cohort had higher risk of MACE even though they were younger and generally healthier (χ 0.02) Similar risk among unopposed estrogen vs estrogen/progesterone combo 3.2 fold increase in stroke among HRT patients Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The stroke Prevention in Atrial fibrillation (SPAF) Investigators. Stroke. 1999; 30(6):

16 Does menapausal state contribute to increased risk of stroke? Loss of estrogen receptor on platelets in animal models Enhanced platelet adhesion (via increased vwf) Enhanced platelet activation (via increased P-selectin expression) Enhanced platelet aggregation (via increased fibrinogen receptor) Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The stroke Prevention in Atrial fibrillation (SPAF) Investigators. Stroke. 1999; 30(6):

17 Women and AFIB: summary Risk calculators that include gender generally perform better (such as Framingham and CHADS2VASC) versus those that do not (AFI and CHADS2) Afib diagnosis among women is associated with greater odds ratio of mortality than among male patients Afib diagnosis among women is associated with greater odds ratio of mortality than among male patients Hormone replacement therapy is associated with greater risk of stroke among patients with afib (who are not anticoagulated)

18 Clinical Question 3: Aspirin and Primary Prevention in the worried well post-menopausal woman You meet for the first time a 60 year old asymptomatic woman for routine physical exam; she has healthy blood pressure and lipid panel. Her exam shows that she is overweight (BMI 27), but exam is otherwise benign; she exercises regularly and does not take any prescription medications She is worried because her mother who is morbidly obese, had CABG at age 60. Do you recommend aspirin for primary prevention of coronary artery disease? Yes No

19 Women s Health Study women took Aspirin took Placebo 477 MACE healthy 522 MACE healthy MACE event rate was low in this primary prevention trial (about 2% in 10 years) Aspirin arm failed to show reduced MACE rate Subgroup analysis showed that sicker women (ie women with greater event rate) showed greatest benefit from aspirin. >65 years old Hyperlipidemia Hypertension Ridker PM, Cook NR, Lee I, Gordon D et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. NEJM 2005; 325:

20 Among healthy women aspirin protects from stroke, but not necessarily from myocardial infarction Ridker PM, Cook NR, Lee I, Gordon D et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. NEJM 2005; 325:

21 Subgroup Analysis of WHS Ridker PM, Cook NR, Lee I, Gordon D et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. NEJM 2005; 325:

22 WHS: Aspirin Reduces the risk of stroke Aspirin No Aspirin Stroke 221 (1.1%) 266 (1.3%) No Stroke Total Women assigned to aspirin arm of the study had slightly lower but statistically significant reduced risk of stroke Absolute Risk reduction 0.27% NNT=365; which means 365 women need to take aspirin 100 mg every other day for 10 years to prevent 1 stroke Ridker PM, Cook NR, Lee I, Gordon D et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. NEJM 2005; 325:

23 US Preventative Services Task Force recommendations: aspirin for primary prevention in men vs women

24 Aspirin for primary prevention in women: summary Among healthy women >45, aspirin therapy assignment failed to demonstrate reduced risk of myocardial infarction in WHS a large RCT Assignment to aspirin treatment at 100 mg every other day resulted in modest reduction in stroke risk Greatest benefit for MACE prevention was demonstrated among women >65; while they constituted only 10% of patients, they contributed to 44% of MACE. For our particular worried well patient, I would counsel her against aspirin for primary prevention; this topic can be revisited once she turns 65.

25 Clinical Question 4: Supplements and Primary Prevention in the worried well post-menapausal woman Your 60 year old asymptomatic patient wants to discuss the role of supplements in primary prevention While she does not take any prescription medications, she takes calcium carbonate (1200 mg of elemental calcium) daily. She does not have osteoporosis or previously documented fracture What do you tell her about calcium supplements and risk of coronary artery disease? Stop calcium supplement; it has been shown to increase risk of MI Keep calcium going; there is no documented risk

26 Iowa Women s Study: Supplement Use in Post-Menapausal Women 100% 75% 50% 25% 0% percentage of women who take at least one supplement percentage of women who take calcium supplement Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR. Dietary supplements and mortality rate in order women: the Iowa women s health study. Arch Intern Med. 2011; 171(18):

27 Calcium Supplementation Results Increased Risk of MI Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691

28 Calcium Supplementation Calcium Placebo MI 166 (2.7%) 130 (2.2%) Healthy Total Women assigned calcium supplement had slightly higher but statistically significant increased risk of heart attack Absolute Risk increase 0.5% Number Needed to Harm =211; which means 211 women need to take calcium to cause 1 heart attack Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691

29 Calcium Supplementation in Post- Menapausal Women: summary Among healthy post- menapausal women, calcium supplementation resulted in increased risk of heart attack in a meta-analysis of 15 randomized control trials While the risk of heart attack is modest, it is statistically significant In the absence of some compelling reason to take calcium, I would advise the patient to discontinue it

30 Thank you for your kind attention