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Traditional and Nontraditional Risk Factors for Cardiovascular Disease in Women

Although women’s awareness about their number one health threat has increased over the past ten years, the percentage remains low.  Even “aware” women often feel exempt and personally not at risk. It is imperative to educate all women on their personal responsibility to know and manage their individual risk factors.  These include traditional risk factors and those that are gender specific. Finally all women must understand that all women are at risk.⁷

Hypertension

The overall prevalence of hypertension is greater in women than men, especially those with a history of hypertension during pregnancy.  Black and Hispanic women are twice as likely to have hypertension.  Diastolic elevation is more common in younger women and favorably responds to exercise.  Oral contraceptives and hormone replacement therapy may increase blood pressure.  Reno-vascular hypertension from fibromuscular dysplasia and autoimmune disorders such as systemic lupus erythematosus are contributing factors.^8,9 

Angiotensin converting enzyme inhibitors or angiotensin receptor blockers are first to be considered in patients with diabetes and may be preferred in post-menopausal women with hypertension.⁷  This is supported by the theory of menopause being associated with a fall in nitric oxide from lack of estrogen receptor stimulation with resultant rise in aldosterone.  Studies suggest this mechanism may account in part for diastolic dysfunction observed in post menopausal women.  Interestingly, women are more likely to experience the ACE inhibitor cough than men as well as develop edema from the vasodilatory effects of calcium channel blockers. 

Diabetes

Diabetes is a more powerful risk factor in women than men.⁷ Abnormal lipid profiles are more likely to be present in diabetic women than diabetic men.  Women with a history of gestational diabetes are at greater risk for developing diabetes later in life.  Metabolic syndrome risk factors, including polycystic ovary syndrome, increases the likelihood of developing diabetes and warrants aggressive screening.  As women transition through menopause, a common occurrence is weight gain and increase in abdominal girth compromising the ability of insulin receptors to govern blood glucose.

Dyslipidemia

While studies have reported statin therapy to be effective in women, dyslipidemia is less likely to be treated in women than men. Changes in cholesterol are associated with menopausal status. Total and LDL cholesterol levels are lower in premenopausal women than in age matched men; following menopause they exceed that of men. A common false assumption is that women can ignore elevated total and LDL cholesterol if their HDL cholesterol and total cholesterol to HDL ratio are ideal.⁷  As with anti-hypertension medication prescriptions, women are less likely to fill and use a prescription for cholesterol lowering therapy.

Nicotine Abuse

Women who smoke are more likely than men to suffer a myocardial infarction and this occurs twenty years earlier than in women who do not smoke.  The most common reason women won’t stop smoking is related to their fear of gaining weight.  Nicotine and supplemental hormones, either in the form of contraception or hormone replacement, are a deadly combination and the leading cause of myocardial infarction in young women.

Obesity

Obesity is an independent risk factor for cardiovascular disease, most prevalent in black women, followed by Hispanic and white women.  Those with abdominal obesity and increased waist to hip ratio carry an even greater risk of cardiovascular disease even among women of normal weight. This suggests that maintaining a normal waist size may be as or even more important as weight control.  Excess adipose tissue results in overproduction of adipokines which are potent mediators of inflammatory factors that are associated with increased cardiovascular risks.

Family History

History of myocardial infarction in primary family members is an independent risk factor for cardiovascular disease. There is evidence to suggest a history of maternal myocardial infarction, regardless of age, carries an increased risk for cardiovascular events.

Oral Hygiene

Evidence correlates periodontal disease with atherosclerosis. Gingivitis becomes more prevalent in the post-menopausal woman and should be aggressively treated.  

Depression

The Nurses Health Study reported that physically healthy women with symptoms of depression had an increased risk of future cardiovascular events.¹⁰  Young women, less than sixty years of age, have the highest prevalence of depression following myocardial infarction and may account for the lowest attendance in cardiac rehabilitation and poorer outcomes.  C-reactive protein is increased in patients with depression and down regulates endothelial nitric oxide production.  Associated abnormal serotonin levels may lead to platelet aggregation and prescription of selective serotonin reuptake inhibitors has been shown to reduce cardiovascular mortality.

Immune System Disorders

Autoimmune disorders, including rheumatoid arthritis and systemic lupus erythematosus, carry an increased risk of premature coronary artery disease. Young women with lupus have a fifty time greater risk of myocardial infarction compared to healthy women in the same age group. These inflammatory states are associated with spontaneous plaque rupture and therapies that reduce inflammation reduce cardiac risk.  Considering lupus as a coronary artery disease equivalent has recently been proposed, placing these women in the high risk category.

Cancer Therapies

Doxorubicin (Adriamycin) and trastuzumab (Herceptin), chemotherapy agents administered for treatment of breast cancer, have potential cardiotoxic effects which can result in cardiomyopathy and congestive heart failure.  Radiation to the chest can cause myocardial restriction and pericardial constriction. Radiation-induced coronary artery and valvular disease may require surgical intervention.  Cardiac complications manifest clinically ten or more years following radiation therapy and may be more likely to occur in those receiving therapy for left sided breast cancer. 

Hormonal status

Menopause, whether it is natural or surgical, is a risk factor all women share and is associated with accelerating risk for cardiovascular disease.⁷ Estrogen receptors are present throughout the cardiovascular system. As estrogen circulates and binds to these receptors, vasodilation via nitric oxide occurs. This relationship creates a healthy vasculature, promoting relaxation with antioxidant properties. As circulating hormonal levels fluctuate, whether related to hormone therapy, menstrual cycle, pregnancy, perimenopause, natural or surgical menopause, variable physiologic responses occur.  This can result in a multitude of symptoms including palpitations, chest discomfort and account for potential increased risk of cardiovascular events.  Fluctuations in circulating reproductive hormones can trigger endothelial dysfunction.  Women with vasomotor disorders such as migraine headaches and Raynaud’s Disease may note exacerbation of their symptoms depending on the stage of menstrual cycle.  Chest discomfort just prior to menses may be related to coronary artery spasm.  Spontaneous dissection and acute coronary syndromes are more likely to occur in this phase of the menstrual cycle. 

The post-menopausal woman with hypertension and diabetes is most likely to experience symptomatic diastolic dysfunction.  Shortness of breath, especially with quick acceleration and climbing stairs is commonly reported.  Women may experience microvascular angina with abnormal coronary flow reserve.  Diastolic dysfunction is a trigger for atrial fibrillation.  Strict risk factor control and exercise have favorable effects on diastolic function.  Congestive heart failure is the most common diagnosis for adult hospitalization and diastolic rather than systolic congestive heart failure is more common in women. 

Recent studies suggest hormone replacement therapy should not be used with the expectation of cardiovascular protection.  Rather, women should consider hormone therapy for relief of menopausal symptoms and to use the lowest dose for the shortest duration.^11-14 

Summary

Cardiovascular disease is the number one health threat to women. (See book review above.) Women of all ages and ethnic cultures need to proactive about their own heart health and take responsibility to reduce  their risk factors.  In addition to traditional risk factors, women need to be aware of other clinical conditions that can impact their cardiovascular health.

Book Review

Cardiovascular Disease in Women Essentials
By Kevin A. Bybee, MD, Michelle L. Dew, MD, Stephanie L. Lawhorn, MD & Tracy L. Stevens, MD
Saint Luke’s Mid America Heart Institute, Kansas City, Missouri
Publisher: 2012 Jones & Bartlett Learning
133 pages

Cardiovascular disease (CVD) is the largest single cause of death among women, accounting for one third of all deaths. In the United States, more women than men die every year of CVD. In the United States, 38.2 million women (34%) are living with CVD, and the population at risk is even larger. Cardiovascular Disease in Women Essentials is a current, concise, and authoritative guide to the diagnosis, treatment and management of cardiovascular disease in women. This pocket-size, quick reference is an ideal resource for primary care physicians, cardiologists, internal medicine physicians, and physicians in training.

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