Over the past several years, a 30% decline in cardiovascular mortality for American women has been observed.¹ An analysis from the Centers for Disease Control concluded that approximately half of the improvement in coronary heart disease death rates in the United States from 1980 and 2000 was due to better control of major risk factors, including reductions in total cholesterol, systolic blood pressure, and smoking prevalence.² The other half was ascribed to disease-based treatments, which accounted for 11% of the improvement in mortality. In 2004, the American Heart Association issued the first evidence-based guidelines for cardiovascular disease (CVD) prevention in women.³ A 2011 update found few gender differences in the efficacy of preventive interventions, but data evaluating parity in safety or cost-effectiveness were limited.⁴ Although concern about secondary prevention in women has been reconsidered due to reports of higher mortality after a myocardial infarction, subsequent risk adjustments have found no mortality difference in most recent studies.

Despite such advances, CVD remains the leading cause of morbidity and mortality in women, affecting 6.6 million women every year.⁵ Sex differences in clinical presentation and treatment among patients with acute coronary syndrome (ACS) have been extensively reported,^6,7 and subsequently secondary preventative measures are of great interest. Although in-hospital treatments of women clearly differ from that of men with ACS, this may be related to sex differences in the etiology of ACS, with less obstructive coronary disease observed in women. Once a significant coronary stenosis has been identified, women are offered revascularization as frequently as men, and post-stent prescribing of medications is identical between men and women.⁸

The Danish National Patient Registry is one of the world's oldest nationwide hospital registries and is used extensively for research. One of these registries evaluated 20,800 patients hospitalized with acute myocardial infarction (AMI) in which there were 834 women and 761 men who initially presented with ST-elevation myocardial infarction without significant coronary stenosis. All-cause mortality, recurrent AMI, and redeeming a prescription for a lipid-lowering drug, beta-blocker, clopidogrel, or aspirin with 60 days of discharge was similar in men and women.⁹

Similarly, in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, women with coronary disease were prescribed drugs similar to men. Despite equivalent treatment, women less frequently met targets for HbA1c and low-density lipoprotein cholesterol (LDL-C).⁸ These findings suggest that there may be sex differences in patient compliance or response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia.

The European Society of Cardiology has carried out surveys with the acronym EUROASPIRE (European Action on Secondary and Primary Prevention through Intervention to Reduce Events). EUROASPIRE III interviewed and performed clinical and biochemical tests at baseline and 6 months after hospital admission in 8,966 patients (25.3% women). Despite similarities in medication exposure, women were less likely than men to achieve blood pressure, LDL-C, and HbA1c targets after a coronary event. This gap did not appear to narrow between 1994 and 2007.¹⁰ In EUROASPIRE IV, it was concluded that risk factor control was inadequate despite high reported use of medications.¹¹ Less than half of the coronary patients accessed cardiac prevention and rehabilitation programs. Whereas sex differences in coronary heart disease treatment were minimal, substantial differences were found regarding target achievement. The largest difference was seen in less educated and elderly female patients. These data suggest an educational or compliance issue with women, rather than a physician prescribing bias.

In a retrospective population-based cohort study using linked administrative data sets in British Columbia, all individuals who survived for 1 year after AMI in 2007–2009 were followed.¹² Patients were evaluated for whether they initiated and then subsequently refilled prescriptions for angiotensin-converting enzyme inhibitors, beta-blockers, and statins. The study found that women <55 years were less likely to be on optimal therapy by the end of 1 year, which was driven by a sex disparity in treatment initiation. However, for other age groups, slight under initiation of therapy among women seemed to be offset by lower adherence to treatment among men. Overall, the majority of AMI survivors either discontinued treatment or did not refill their prescriptions consistently, suggesting that further improvements in post-AMI compliance are necessary for both men and women.¹²

Completion of a cardiac rehabilitation programs is both a life-saving and life-enhancing opportunity. Despite the evidence of long-term health benefits, a minority of patients participate in cardiac rehabilitation.¹³ The participation rate is particularly low in women, and one study reported that despite referral from a physician, attendance rates for women are 50.1%, compared with 60.4% of men. Furthermore, women are twice as likely not to complete a rehabilitation program compared with men, as shown in Figure 1.

Figure 1

Some have speculated that risk factor management might be different based on the sex of the physician. Despite more female physicians documenting diet, prescribing weight loss, providing more physical activity counseling, the quality of care as measured by patients meeting CVD risk factors treatment goals was similar regardless of the sex of the patient or physician.^14-16

In fact, in one study, women at high cardiovascular risk appeared to have better outcomes than men, with reduced risk-adjusted rates of myocardial infarction and cardiovascular death.¹⁷ Moreover, recently reported age-adjusted national cardiovascular mortality rates were lower in women than men, and the continued decline of mortality in both sexes suggest that appropriate secondary prevention measures are not being withheld from women.¹⁸

Therefore, based upon review of the literature and prior studies, we believe that secondary prevention measures for women are being appropriately prescribed according to the guidelines and recommendations available. However, women appear to be less likely to reach certain targets of secondary prevention. This may be due to non-compliance, poor adherence, gender difference in drug metabolism, discontinuation due to more side effects, or actually measuring the wrong end-goal (e.g., total cholesterol instead of LDL-C).

Further research related to the age and gender relationship should include sex-specific biology, clinical manifestations, and an improved understanding of the environmental and social factors that may increase compliance among women. Research gaps exist related to coronary pathophysiology, optimal diagnostic testing (imaging), optimal pharmacologic and interventional strategies, primary and secondary prevention for CVD, and the understanding of race/ethnicity, socioeconomic, and psychological factors. Thus, women's cardiovascular health requires a multidisciplinary approach to both research and clinical activities.

References

1. Hahn J, Lessard D, Yarzebski J, et al. A community-wide perspective into changing trends in the utilization of diagnostic and interventional procedures in patients hospitalized with acute myocardial infarction. Am Heart J 2007;153:594-605.
2. Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980-2000. N Engl J Med 2007;356:2388-98.
3. Mosca L, Appel LJ, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004;109:672-93.
4. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the american heart association. Circulation 2011;123:1243-62.
5. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation 2016;133:e38-360.
6. Dey S, Flather MD, Devlin G, et al. Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events. Heart 2009;95:20-6.
7. Graham G. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes. Clin Med Insights Cardiol 2016;10:1-10.
8. Magee MF, Tamis-Holland JE, Lu J, et al. Sex, Prescribing Practices and Guideline Recommended, Blood Pressure, and LDL Cholesterol Targets at Baseline in the BARI 2D Trial. Int J Endocrinol 2015;2015:610239.
9. Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 2015;7:449-90.
10. Kotseva K. Lessons from EUROASPIRE I, II, and III surveys. Heart Metab 2011;50:32-35.
11. Kotseva K, Wood D, De Bacquer D, et al. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol 2016;23:636-48.
12. Smolina K, Ball L, Humphries KH, Khan N, Morgan SG, et al. Sex Disparities in Post-Acute Myocardial Infarction Pharmacologic Treatment Initiation and Adherence: Problem for Young Women. Circ Cardiovasc Qual Outcomes 2015;8:586-92.
13. Witt BJ1, Jacobsen SJ, Weston SA, et al. Cardiac rehabilitation after myocardial infarction in the community. J Am Coll Cardiol 20014;44:988-96.
14. Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med 2001;345:892-902.
15. Jolliffe JA, Rees K, Taylor RS, Thompson D, Oldridge N, Ebrahim S. Exercise-based rehabilitation for coronary heart disease. Cochrane Database Syst Rev 2001;1:CD001800.
16. Lawler PR, Filion KB, Eisenberg MJ. Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Am Heart J 2011;162:571-84.e2.
17. Lam CS, Little WC. Sex and cardiovascular risk: are women advantaged or men disadvantaged? Circulation 2012;126:913-5.
18. Mensah GA, Wei GS, Sorlie PD, et al. Decline in Cardiovascular Mortality: Possible Causes and Implications. Circ Res 2017;120:366-80.

Keywords: Acute Coronary Syndrome, Female, Risk Factors, Cholesterol, LDL, Angiotensin-Converting Enzyme Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Aspirin, Blood Pressure, Glycated Hemoglobin A, Secondary Prevention, Cardiac Rehabilitation, Cardiovascular Diseases, Risk Adjustment, Sex Characteristics, Retrospective Studies, Cost-Benefit Analysis, Myocardial Infarction, Weight Loss, Patient Compliance, Registries, Angioplasty, Hypertension, Coronary Stenosis, Hyperlipidemias, Primary Prevention, Stents, Diabetes Mellitus, Referral and Consultation, Diet

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