Sex differences in clinical characteristics and long-term outcomes in patients with vasospastic angina: results from the VA-Korea registry, a prospective multi-center cohort

Abstract

Background Sex differences in clinical characteristics and prognosis of vasospastic angina (VA) have not been well elucidated. This study was performed to investigate sex-specific characteristics and predictors for long-term clinical outcomes in patients with VA. Methods We analyzed 1838 patients (55 years and 62% male) who were diagnosed with definite (n = 680) or intermediate (n = 1212) VA in ergonovine provocation test from a nation-wide VA registry. The primary study end-point was composite events including cardiac death, acute coronary syndrome, ventricular tachycardia or fibrillation, and atrioventricular block during clinical follow-up. Results Male patients were younger, and there were more smokers and alcohol drinkers in male patients than in female patients. During the median follow-up period of 760 days (interquartile range, 336–1105 days), there were 73 cases (3.97%) of composite events. There was no sex difference in the occurrence of composite events (log-rank p = 0.649). Concomitant significant (≥ 50%) organic coronary stenosis was associated with worse clinical outcomes in both male (hazard ration [HR], 1.97; 95% confidence interval [CI], 1.01–3.85; p = 0.047) and female (HR, 3.26; 95% CI, 1.07–9.89; p = 0.037) patients. Obesity (body mass index ≥ 25 kg/m2) was associated with better prognosis in female VA patients (HR, 0.22; 95% CI, 0.07–0.68; p = 0.008). Even when only patients with definite diagnosis of VA were considered, there was no significant sex difference in clinical outcomes (log-rank p = 0.876). Conclusions In VA patients, there were several different clinical characteristics according to sex; however, long-term clinical outcome was similar between sexes. Significant organic coronary stenosis in both sexes and low body mass index (< 25 kg/m2) in females were associated with worse prognosis in VA patients.

Current Evidence on Long-Term Prognostic Factors in Vasospastic Angina

“…It has been reported that young age (<50 years) was associated with better clinical outcomes in female VSA patients but not in male VSA patients, which suggests the important role of female sex hormones in cardiovascular protective effects [16]. However, unlike these studies, in some studies, age was not related to the long-term prognosis in patients with VSA [22,23]. Another study, rather, has reported that older age is associated with a better prognosis of VSA [24].…”

“…The VSA prognosis is expected to be worse in men than in women because men smoke and drink more and have a higher prevalence of accompanying organic stenosis [ 16 , 22 , 26 ]. However, results from prior studies on this issue were different from our expectations.…”

“…Therefore, combined organic stenosis is one of the important prognostic factors for patients with VSA. Many studies have shown that the extent and severity of combined atherosclerotic coronary artery disease (CAD) was one of the independent prognostic factors of cardiovascular outcome in VSA patients [ 5 , 13 , 17 , 22 , 24 , 37 ]. In a study that followed 169 VSA patients, survival for patients with multi-vessel disease was 81%, 76%, and 66%; for patients with one-vessel disease, 97%, 92%, and 92%; and for patients without significant stenosis, 98%, 98%, and 98% at 1, 2, and 3 years, respectively [ 13 ].…”

“…Kim et al analyzed 1920 VSA patients and found that significant stenosis was an independent risk factor for long-term prognosis (1-year MACE rate: 5.8% vs. 1.4%) [ 24 ]. In the sex-specific analysis using the same database, combined organic stenosis was significantly associated with long-term clinical outcomes in both male and female patients with VSA [ 22 ]. According to the results of a recent study of 175 Japanese patients with VSA, those with organic stenosis with a fractional flow reserve of ≤0.80 showed a higher MACE rate compared to those without organic stenosis during a median follow-up period of 656 days (37.6% vs. 3.6%) [ 37 ].…”

“…Similar findings were also found in other studies [ 56 , 57 ]. It has been reported that long-term prognosis was worse in VSA patients with a coronary spasm that occurred at the site of organic stenosis compared to those with a coronary spasm occurring at a site other than the site of a significant organic stenosis [ 5 , 22 , 58 ]. A coronary artery spasm is common in the segment of myocardial bridging because it is frequently accompanied by endothelial cell dysfunction [ 59 , 60 , 61 ].…”