Sex Differences in the Heart Whitehead Institute Seminar Series: Sex Differences in Health and Disease March 2, 2020 Emily S. Lau, MD Department of Medicine, Cardiology Division, Massachusetts General Hospital Department of Medicine, Brigham and Women’s Hospital
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Sex Differences in the HeartWhitehead Institute Seminar Series: Sex Differences in Health and Disease
March 2, 2020
Emily S. Lau, MD Department of Medicine, Cardiology Division, Massachusetts General Hospital
Department of Medicine, Brigham and Women’s Hospital
• Heart disease in women • The estrogen story • Sex differences in heart failure
OUTLINE
• Heart disease in women • The estrogen story • Sex differences in heart failure
OUTLINE
Cardiovascular mortality trends for men and women in the US: 1979-2015
Circulation 2018;137:e67-e492
A closer look at the heart
ARTERIES
PUMP RHYTHM
VALVES
Sex differences in cardiovascular disease
ARTERIES VALVES RHYTHM PUMP
• Lower incidence of CAD and ACS
• Microvascular disease common
• Present later in life • Tricuspid
regurgitation more common
• Atrial fibrillation less common, but higher stroke rate
• Non-ischemic etiology
• Preserved LVEF
Circulating biomarkers differ in men and women
JACC 2019; 74(12): 1543-1553
• Heart disease in women • The estrogen story • Sex differences in heart failure
OUTLINE
Heart disease rises precipitously post-menopause
CAD
Stroke
AJMC 2000: 6(14 Suppl):S746-60
Estrogen signaling
Circ Research 2001; 109:687-696
Estrogen and the cardiovascular system
ATHEROSCLEROSIS
↓ LDL oxidation ↓ LDL binding↑ BP ↓ oxidative damage↓ VSMC proliferation
THROMBOSIS
↑ coagulation factors ↓ platelet aggregation
VASOREACTIVITY ARRHYTHMIAS
QT prolongation↑ vasodilation↑ nitric oxide ↓ endothelin↑ COX2 ↓ neuroendocrine
response↓ VSMC proliferation
JACC 2009; 53:221-31
Group Major Coronary Disease RR (95% CI)
Fatal CV DiseaseRR (95% CI)
Current HRT use, adj for age 0.51 (0.37-0.70) 0.48 (0.31-0.74)
Current HRT use, adj for age and RFs 0.56 (0.40-0.80) 0.61 (0.37-1.00)
Hormone therapy reduced heart disease in observational studies
NEJM 1991; 325:756-62
Estrogen plus progestin
Placebo
Cum
ulat
ive
haza
rd o
f CHD
Years of followup
HR 1.24 (0.97-1.60)
Estrogen + progestin in healthy postmenopausal women
Estrogen in postmenopausal women with hysterectomy
Estrogen
HR 1.39 (1.10-1.77)
Placebo
Cum
ulat
ive
haza
rd o
f str
oke
Years of followup
Hormone therapy increased CV events in randomized controlled trials!
N Engl J Med 2003;349:523-34JAMA 2004; 291(14):1701-12
Menopause and hormone status influence circulating biomarkers
ß-coefficient
1. Women2. Pre-menopausal women3. Post-menopausal women4. Women not on HRT5. Women on HRT
Higher in men Higher in women
1 2 3 4 5 JACC 2019; 74(12): 1543-1553
Estrogen and the cardiovascular system
Circ Research 2001; 109:687-696
• Heart disease in women • The estrogen story • Sex differences in heart failure
OUTLINE
Sex differences in heart failure
ARTERIES
PUMP RHYTHM
VALVES
Two types of heart failure
Reduced ejection fraction Preserved ejection fraction
Stiff ventricle wallsWeakened ventricle
Less blood is pumped out
Less blood enters the ventricles
Myocardial remodeling in HFrEF vs HFpEF
JACC 2013; 62:263-71
HFrEF HFpEF
Lifetime risk of developing HF is similar in men and women
Circulation 2002:106;3068-3072
HFpEF is more prevalent in women than men
Eur J Heart Fail 2002;4:531-539
HFrEFHFpEF
Women develop greater cardiac hypertrophy with age than men
Circulation 2009; 119(24):3085-3092
Obesity associates with risk of HFpEF, especially in women
JACC HF 2018; 6(8):701-709
Women develop HFpEF at lower burden of comorbidities
JAMA Cardiol 2020;5(1):30-37
Cardiopulmonary Exercise Test (CPET)
Pulmonary artery catheter Face mask Radial artery
catheter
Circulation 2013; 127:1157-1164
Exercise responses in men and women with HFpEF
JAMA Cardiol 2020;5(1):30-37
Lung
sH
eart,
Blo
od,
Vasc
ulat
ure
Mus
cle
Women with HFpEF have lower quality of life
J Card Fail 2020; S1071-9164(19)30785-7
…but better survival
Circ Heart Failure 2012;5:571-578
Sex differences in heart failure
Eur Heart Journal
Conclusions: From bedside to bench
Heart disease is different in men and women Sex differences in biomarkers: biological pathways differentially activated in men & women
CVD risk increases after menopause but estrogen does not reduce risk
Menopause and hormone status may affect certain biological pathways but not all
Heart failure with preserved ejection fraction is more common in women
Women are more susceptible to the deleterious effects of HTN, obesity and diabetes.
We need more research in women from animal studies to randomized trials!
Heart disease is not just a man’s disease = leading cause of death in women
Thank you!
Jennifer HoAnthony RosenzweigSamantha Paniagua Elizabeth LiuSawalla GusehShahrooz ZarbafianGregory Lewis Matthew Nayor Lisa CurrieriMalissa Wood Nandita ScottAmy SarmaMichael Honigberg
Marcelo DiCarliCourtney Bibbo
Ho Lab 2018
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