Gender-specific medicine may perhaps be the newest subspecialty in cardiology to emerge in the very near future. Almost 20 years ago in my book, Heart Sense for Women,¹ I discussed the differentiation of symptoms and presentation of heart disease for women, which we long thought to be the same as they were for men. The genders are definitely different not only in diagnosis and treatment, but prognosis as well.

Although women are generally better in touch with their physical and emotional pain than men are, they tend to experience more subtle or vague nondescript physical symptoms of heart disease compared to their male counterparts. As myocardial ischemia may be manifested as both typical and atypical symptoms in women, in my experience, making the diagnosis of angina—as well as myocardial infarction—is a more complex and a poorly understood process.

In general, most men may experience a dramatic crushing substernal pain in their chest—with or without radiation to the left shoulder and/or left elbow area—or extreme shortness of breath when having a myocardial infarction. But women’s symptoms may be more vague including the following:

Although some men may have any of the above symptoms as well, they are more subtle in presentation for women. For example, I recently heard from a woman colleague in her 60s. She had called to share her experience of having a very recent and unexpected myocardial infarction in the middle of the night, she was awakened with profound nausea and vomiting. The unexplained symptoms dissipated. She realized that there was no apparent reason for the “attack”: no real reason to suspect food poisoning or stomach flu. So, she went back to bed. A few days later she awoke again. The profuse sweating was then accompanied by some ill-defined chest discomfort. She experienced extreme dread, which can be another hallmark sign.

Dangerously, she drove herself to an urgent care center where both her electrocardiogram and blood tests confirmed the diagnosis of myocardial infarction. The damage was caused by a blockage in her circumflex coronary artery, a location much preferable to the left anterior descending, which would have resulted in more significant myocardial damage. She was successfully stented and fortunately had a “happy ending.”

Although her prognosis remained good for the future, she was also placed on statin therapy, despite the fact that she had a cholesterol level within normal limits. Generally speaking, I am not a big fan of giving statin drugs to women because the risk/benefit ratio is just not in their favor. However, in situations of an acute coronary artery syndrome or preinfarction angina, continuation of statins in the coronary care unit (CCU) or intensive care unit (ICU) is strongly recommended as the pleotropic effects are especially noteworthy in overall survival. Although these blood thinning, antioxidant, and pleotropic properties of statins may be beneficial to some women, many more women compared to men develop intolerable side effects in the musculoskeletal system, developing weakness and myalgias.² In addition, calcification of the coronaries,³ diabetes,⁴ and even breast cancer⁵ are all problematic for women on long-term statin therapy. In fact, a 2010
meta-analysis⁶ found that statin therapy actually increased rather than decreased coronary artery disease (CAD) risk in women. Although it is well known that statins deplete precious nutrients like coenzyme Q10, vitamins D and E, zinc, and magnesium, to mention a few, the inhibition of vitamin K2, the cofactor for matrix and Gla-protein activation, and the decline in the biosynthesis of selenium-containing proteins (glutathione peroxidase) creates a possible ominous scenario.⁷ Indeed this undesirable effect of artherosclerosis and heart failure by the pervasive use of statin drugs must be considered by the astute physician.⁷ However, in men younger than 75 years with proven CAD, I do prefer a low-dose statin in combination with multivitamin/multimineral support and Coenzyme Q10 therapy. Like Coenzyme Q10, statins have favorable antioxidant, blood thinning, and anti-inflammatory properties which certainly appear promising for younger men. In my experience, the risk/benefit is worth the possible side effects, which is less intense than it is in women.⁸ The use of statins warrants careful scrutiny as a gender-specific intervention. In the most recent study on statin therapy in the primary prevention of CAD, statin medications provided no clinical benefit when prior coronary artery calcium score was zero in a retrospective analysis of 13,644 patients.⁹

To further complicate the diagnosis and prognosis of heart disease in women, observational findings reported in a very recent medical communication how women physicians do a better job assessing other women presenting in urgent care centers who are experiencing chest pain than male physicians. Additionally, women patients are more likely to survive a myocardial infarction if their treatment is administered and overseen by female doctors.¹⁰ This fact that women physicians have more success treating female patients is interesting. Perhaps women physicians are not only more intuitive, but more empathic as well than their male counterparts. Certainly, more research is needed in gender concordance situations.

Even though studies warrant that more consideration be given to females with heart disease symptoms, it still may take some time to help eradicate so many years of bias. For years, it has been generally thought that women are not serious candidates for CAD. For example, the difference in the use of percutaneous coronary artery (PTCA) intervention in acute MI in females demonstrated delay as the women in this study waited approximately 37 minutes longer before contacting emergency medical services.¹¹ In this study of 4360 patients (967 females) from 2006 to 2016, the 37-minute delay was costly in that the mortality rate in women was 5.9% versus that in men at 4.5%. Any invasive cardiologist knows that every minute counts when the blood supply in an area of the myocardium is obstructed. Since a woman’s coronary anatomy is also somewhat smaller than a man’s, PTCA and stenting may be more problematic with additional morbidity and mortality. In addition to realizing these gender-specific differences in myocardial ischemia between women and men, other major female cardiovascular concerns in this day and age include diastolic dysfunction (DD), hypertension, mitral valve prolapse (MVP), and peripheral artery disease (PAD).

In over 40 years of practicing cardiology, diastolic dysfunction (DD) is perhaps the most poorly understood pathological situation affecting both men and women. It is definitely the most impressive predisposing factor leading to systolic and eventually global left ventricular dysfunction. Most patients (females more so than males) with DD have normal or near-normal left ventricular ejection fractions.¹²,¹³ Many of these patients experience the same signs and symptoms as patients with heart failure and reduced ejection fraction. Symptomatic suffering and unacceptable quality of life are reported in many of these patients.¹⁴,¹⁵

Diastolic heart failure results from compliance issues or a “stiffening of heart muscle.” The left ventricle does not fill properly with blood and during diastole the filling cycle struggles and heart is somewhat energetically compromised. Patients may feel shortness of breath and fatigue and some even experience chest discomfort as well as peripheral edema. Their symptoms and physical findings are similar to patients with systolic heart failure caused by a weakened heart, and their prognosis remains guarded.¹²,¹³ The mortality and morbidity caused by DD, which is also referred to as heart failure with well-preserved systolic function, is very similar to systolic heart failure. Approximately a decade ago, the estimated healthcare costs were $30 billion in the United States alone. Thus DD and systolic dysfunction place a great burden on our healthcare system.¹⁶

The identification of effective treatments for diastolic heart failure remains an important area of investigation and concern given the predominance of women with diastolic heart failure,¹⁷ lack of specific therapies,¹⁸,¹⁹ and high mortality and morbidity associated with this affliction.¹²,¹³ A shocking projective occurrence statistic for this heart failure epidemic was estimated to be 20% in those older than 40 years.¹⁴

The treatment for DD continues to be disappointedly and severely limited as pharmaceutical drugs have been shown to be of little benefit in randomized clinical studies.²⁰ This Women’s Health Coalition Report²⁰ also documented on the lack of effective treatments for DD and indicated that the prognosis has not changed for the last 15 years.

However, since the advent of the Treatment of Preserved Cardiac Function Heart Failure (TOPCAT) Trial (2014),²¹ new pharmaceutical enthusiasm for spironolactone has emerged. Although treatment did not significantly reduce deaths for preserved ejection fraction,²¹ in those patients at the lower end of the left ventricular ejection fraction (LVEF) spectrum (LVEF of 40%-50%), the effect of spironolactone was somewhat significant.²²

Similar findings were seen in a post hoc subgroup in the PEACE Trial in which angiotensin-converting enzyme (ACE) inhibitors resulted in a benefit in patients with ischemic cardiomyopathy and midrange LVEF of 40% to 50%.²²,²³ In another analysis of TOPCAT mineralocorticoid receptor antagonists can be considered to reduce risk of heart failure hospitalization in selected patients with preserved
ejection fraction (HFpEF).²⁴ Although these recent trials suggest some benefit from pharmaceutical therapies on patient outcomes, clearly a more suitable alternative metabolic approach is needed to treat any patient with DD and/or systolic dysfunction.