Impact of Sex on Cardiovascular Outcome in Patients at High Cardiovascular Risk

Abstract

Background-Epidemiological data suggest that sex independently contributes to cardiovascular risk. Clinical trials are often hampered by the enrollment of few female patients. Methods and Results-The Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial(ONTARGET) and the parallel Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) included a large proportion of female patients (9378 female versus 22 168 male patients). Differences in male and female patients enrolled in ONTARGET/TRANSCEND were analyzed for the primary 4-fold end point (composite of cardiovascular death, myocardial infarction, stroke, or admission to hospital for heart failure), a secondary 3-fold end point (cardiovascular death, myocardial infarction, stroke), and individual components of the primary composite. Baseline characteristics included age, ethnicity, body mass index, physical activity, tobacco use, alcohol consumption, formal education, clinical diagnosis for study entry, patient history, and concomitant medication. Patients were followed up until death or the end of the study (median, 56 months). Compared with male patients, female patients had a 19% significantly lower risk for the 4-fold end point and 21% for the 3-fold end point (after adjustment for study, treatment, and the above baseline values). Similarly, the adjusted risk for cardiovascular death (17%) and myocardial infarction (22%), but not for stroke and hospitalization for heart failure, was also significantly lower in women. Diabetic female patients were characterized by a higher risk for acute myocardial infarction compared with diabetic male patients, whereas alcohol consumption resulted in significantly lower risk in women. Conclusions-In our analysis made up of 70.3% male and 29.7% female patients, an Ϸ20% lower risk for the combined cardiovascular end points in female patients was observed despite treatment with cardioprotective agents. This difference was driven primarily by a significantly lower incidence of myocardial infarction. Thus, we demonstrate in a large interventional trial that sex greatly affects the occurrence of cardiovascular events in patients with vascular disease or high-risk diabetes mellitus. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00153101.

Diabetes and End-Stage Renal Disease Synergistically Contribute to Increased Incidence of Cardiovascular Events: A Nationwide Follow-up Study During 1998–2009

“…We found that young females without diabetes or ESRD are less likely to develop CV events compared with males of the same age in Taiwanese (Table 2 and Supplementary Table 5), which corroborates previous reports from Western countries (32)(33)(34). While this trend of developing CV events, especially AMI and stroke, persists for women with either diabetes or ESRD alone, strikingly, this advantage for younger women almost totally disappears for those with the combination of both illnesses (Table 2).…”

Application of New Guidelines for the Primary Prevention of Atherosclerotic Cardiovascular Disease in a Korean Population

“…Given the costs, known side effects and public health implications of statin treatment, we conclude that Asian-specific guidelines are needed to avoid unnecessary over treatment in a large number of peoprevalence of cardiovascular disease than men 20) . Most previous statin trials have included few women ( 25%) and either did not report sex-specific results or reported aggregate events (e.g., major coronary events) and not individual outcomes 21) .…”

GPER-1 and Estrogen Receptor-β Ligands Modulate Aldosterone Synthesis

“…Pharmacologic disinhibition of ER␤ unmasks a potent secretagogue effect of E2 that involves GPER-1 and protein kinase A signaling. (Endocrinology 155: 4296 -4304, 2014) F ertile women are at lower risk of cardiovascular (CV) events and have lower blood pressure (BP) values than age-matched men (1, 2); for example, among hypertensive patients recruited in the ONTARGET trial, women had a 22% lower risk for myocardial infarction than men (3). Therefore, estrogens can decrease BP and thereby CV risk, possibly by affecting the renin-angiotensin-aldosterone system and the sympathetic nervous system, which feature major gender-related differences (4).…”