© 2019 Joule Inc. or its licensors CMAJ | FEBRUARY 11, 2019 | VOLUME 191 | ISSUE 6 E159 C ardiovascular disease (CVD), which is largely prevent able, is a leading cause of morbidity and mortality among Canadian women. For this article, we use CVD torefer to ischemic heart disease and stroke. Data for peripheral arterial disease in women are limited and are addressed elsewhere.1 Until now, risk reduction has focused largely on postmenopausal woman with traditional risk factors: diabetes, smoking, hypertension and hyperlipidemia. Consequently, CVD mortality has declined, largely driven by those aged 50 years and older.2 A recent study of 20-year temporal trends in admissions to hospital and deaths caused by atherosclerotic cardiovascular disease in Ontario reported that mortality rates for circulatory diseases in women declined 52.8% between 1994 and 2012.3 However, annual rates of decline were least evident in individuals younger than 50 years of age, suggesting that CVD among younger adults remains a cause for concern.3 The lowest rate of decline in CVD-related mortality and, in some cases, an increase in CVD-related admissions to hospital and mortality have been observed in younger women.3,4 Contemporary Canadian data suggest the gap in cardiovascular mortality between men and women may be closing.5 Yet young women with ST-segment elevation myocardial infarction (MI) have 15%–20% higher rates of death than men of similar age.6 Whether this is related to systematic differences in care or true biological differences, or a combination, is unclear. What is clear is that addressing cardiovascular health in women younger than 50 years of age requires thinking beyond traditional risk factors in primordial prevention. We present a brief overview of sex differences in traditional cardiovascular risk factors and a focused review of key nontraditional risk factors in younger women (i.e., ovarian dysfunction, infertility, reproductive therapies and pregnancy complications). Our approach to gathering evidence is outlined in Box 1. What is the effect of traditional cardiovascular risk factors in young women? A 2018 study concluded that the strongest predictor of acute coronary syndrome in women under the age of 45 years is diabetes (odds ratio [OR] 6.66, 95% confidence interval [CI] 3.47–12.74), followed by hypertension (OR 4.30, 95% CI 3.42–5.38), hypercholesterolemia (OR 3.45 95% CI 2.60–4.29) and smoking (OR 1.63, 95% CI 1.34–1.98).7 This study also found that smoking was more prevalent and other traditional risk factors were less prevalent among young women compared with older women with acute coronary syndrome.7 The INTERHEART study identified diabetes, metabolic syndrome and tobacco use as stronger predictors of ischemic heart disease in women under the age of 50 compared with older women.8 Findings from a 1996 cohort study suggested that, when compared with men, smoking is a relatively stronger risk factor for MI in women less than 45 years of age (relative risk [RR] 7.1 in REVIEW CPD Identifying and managing younger women at high risk of cardiovascular disease Kajenny Srivaratharajah MD MSc, Beth L. Abramson MD MSc n Cite as: CMAJ 2019 February 11;191:E159-63. doi: 10.1503/cmaj.180053 KEY POINTS • Pregnancy-related vascular complications, such as preeclampsia, need to be factored into risk assessment in younger women. • Conditions such as premature ovarian dysfunction, use of reproductive therapies and infertility may increase long-term risk of cardiovascular disease. • Early risk stratification and aggressive management of lifestyle may help mitigate future risk in premenopausal women with high-risk profiles. • Long-term management strategies need to be defined in this population. Box 1: Evidence used in this review We conducted a search of PubMed for articles published in English between July 2008 and July 2018. We used the Medical Subject Heading (MESH) terms “cardiovascular disease” and “young women” for our search. We narrowed the search further by searching for articles involving humans and adults aged 19 to 64 years. This resulted in 7671 hits, which were narrowed down to 6442 by excluding articles with the term “congenital heart defect.” We reviewed the best matched first 300 articles. Relevant articles listed in the reference section of select articles were also reviewed. We discussed the highest level of evidence via randomized controlled trials when available, and where literature was limited, we used observational and case reports. REVIEW E160 CMAJ | FEBRUARY 11, 2019 | VOLUME 191 | ISSUE 6 women v. 2.3 in men).9 Diabetes is also associated with a higher RR for acute coronary syndrome among women than among men (RR 3.50 in women v. 2.06 in men).10 In addition, a multicentre prospective cohort study reported that young women with acute MI had more comorbidities and worse pre-event health status than men.11 A more recent review of this VIRGO study population found that MI with nonobstructive coronary arteries was 5 times more likely to occur in women than men and less likely to be associated with traditional risk factors.12 Similar results were reported in the GENESIS-PRAXY multicentre prospective cohort study involving adults between 18 and 55 years of age, with more nontraditional risk factors among women.13 With respect to sex differences in traditional risk factors, this study showed higher prevalence of diabetes, hypertension and family history of coronary artery disease among women.13 Contemporary data for sex and gender differences in traditional risk factors for stroke or cerebrovascular disease in young adults are limited. Based on observational data of ischemic stroke in individuals less than 50 years of age, hypertension, dyslipidemia and current smoking status are more frequent in men compared with women.14 However, this study also reported higher stroke severity on the Canadian Neurological Scale and overall unfavourable outcomes at discharge in women compared with men. A 2014 systematic review and meta-analysis on stroke and diabetes showed a higher RR in women than men less than 60 years of age.15 Do estrogen and hormone replacement therapy affect cardiovascular disease risk? The incidence of CVD is lower in premenopausal women compared with men of similar age.16 First coronary event(s) occur, on average, 10 years later in women than men.16 Given that women appear to be mostly protected until mid-life, estrogen has been implicated as a protective factor. However, the cardioprotective role of estrogen is complex and not well understood.17 Estrogen has multiple effects on the cardiovascular system, including promotion of vasodilation, antioxidative defence and recovery from vascular injury, thereby reducing the development of atherosclerosis, and preventing cardiomyocyte and endothelial dysfunction.17 Despite theoretical benefits, trials examining the addition of treatment with estrogen afer menopause have not shown a protective benefit for CVD.18 A recent analysis of data of 18-year follow-up of participants from randomized trials suggests that postmenopausal hormone replacement therapy may not be harmful in women, however.19 What is the relation between ovarian dysfunction and risk of ischemic heart disease? Younger women with ovarian dysfunction appear to have an increased risk of CVD.20,21 Women with premature ovarian failure have as much as 80% higher mortality from ischemic heart disease than those who go through menopause at the expected average age range of 49 to 55 years according to prospective research.22 Endothelial dysfunction, dysglycemia, abnormal lipid profile and metabolic syndrome may be potential drivers of elevated risk in this subset of younger women.20,21 Iatrogenic (i.e., surgical and chemical) menopause before the age of 50 years also confers a similar increase in risk of CVD.23 In a small cohort study, hormone replacement therapy in these women was shown to improve endothelial function within 6 months of treatment;24 however, in those with premature ovarian failure, no long-term data on CVD outcomes are available. Polycystic ovarian syndrome is a common endocrine disorder in premenopausal women, with prevalence ranging from 6% to 15%.25 A review of studies involving women with polycystic ovarian syndrome found an increased risk of subclinical atherosclerotic disease, diabetes, dyslipidemia, obesity and endothelial dysfunction.25 Ten-year follow-up in postmenopausal women with polycystic ovarian syndrome or its characteristics did not show higher mortality or adverse cardiovascular events.26 However, there are methodological limitations to this study. Long-term, large-scale data for cardiovascular outcomes are lacking for this group, and this represents an area for future study. Does reproductive therapy increase women’s risk of ischemic heart disease? Limited and conflicting research has examined long-term risk of CVD resulting from infertility and fertility treatments. A 2017 cross-sectional analysis involving women who completed the Framingham Heart Study Third Generation and Omni Cohort 2 Exam 2 (2008–2011) and reported infertility showed that selfreported infertility was associated with CVD risk factors such as elevated body mass index and waist circumference.27 However, an analysis of data from the Women’s Health Initiative Observational Study did not find a history of infertility to be associated with coronary heart disease.28 A 2016 observational study involving women receiving infertility therapy found that failure of therapy was associated with 19% higher annual rates of cardiovascular events.29 Increased thromboembolic events in this group with failure of infertility therapy may explain the elevated future risk.29 Another possibility is that failure of treatment unmasks those with underlying endothelial dysfunction, a known risk factor for future CVD. A 2017 systematic review and meta-analysis of a small number of heterogeneous observational studies examining the association between reproductive therapies and CVD risk reported no increased rates of cardiovascular events.30 Further study is needed to clarify whether it is the state of infertility itself, or reproductive treatment, that is associated with future CVD. As the average age of child-bearing increases along with a rise in the number of women seeking reproductive therapy for infertility, this is a pressing question that must be addressed.
Women of childbearing age have staggeringly low rates of lipid screening OB/GYNs may be key to getting more women screened Date: March 6, 2019 Source: American College of Cardiology Summary: Eight out of 10 women of childbearing age have never had their cholesterol levels checked, despite clear guidelines to get a first lipid blood test early in adulthood, according to new research. Share: FULL STORY Eight out of 10 women of childbearing age have never had their cholesterol levels checked, despite clear guidelines to get a first lipid blood test early in adulthood, according to research being presented at the American College of Cardiology's 68th Annual Scientific Session. The study, which researchers say is the first to highlight real world lipid screening patterns in young women, calls attention to important gaps to optimally identify people with elevated cholesterol levels, as well as those with genetic cholesterol disorders, including familial hypercholesterolemia (FH) and inherited dyslipidemias. Research indicates these conditions may be more common than previously thought, but FH often goes undiagnosed and is first suspected after someone has a heart attack or stroke at a young age. While current guidelines do not recommend cholesterol screening during pregnancy, there is also evidence that high cholesterol is associated with early (preterm) birth and low birth weight babies, in addition to its role in the development of heart disease, stroke and related death. "Not nearly as many people as we think are actually getting cholesterol screening despite very clear recommendations," said Dipika J. Gopal, MD, a fellow in the cardiovascular division at Hospital of the University of Pennsylvania and the study's lead author. "In fact, the number of patients who have ever been screened was staggeringly low, perhaps because they're either not going to their primary care doctor or their doctor isn't ordering the test." Yet, nearly every expectant mom will see a health care provider during pregnancy, Gopal said, presenting a window of opportunity to identify, counsel and treat patients with elevated cholesterol who are at high risk of long-term complications from maternal hyperlipidemia and address possible effects that it can have on fetal well-being, in addition to helping them make heart-healthy changes. "Up to 94 percent of pregnant women interact with a health care provider during pregnancy and after delivery compared to a much smaller percentage of non-pregnant patients within the same age group," Gopal said. "The peri-partum period is a perfect time to capture a population that may otherwise not come into contact with the health system until many years later, perhaps when they have a first cardiovascular complication."
