Shivang R. Desai

Background: Chest pain (CP) in patients with nonobstructive coronary artery disease is a therapeutic challenge affecting morbidity and mortality. We aimed to identify clinical factors associated with CP in this population, hypothesizing that obesity and depressive symptoms are associated with CP. Methods and Results: In 814 patients with angiographically confirmed nonobstructive coronary artery disease, we measured sociodemographic variables, clinical risk factors, medications, and Patient Health Questionnaire 9 scores for depressive symptoms. We assessed CP frequency and prevalence by using all items from the Seattle Angina Questionnaire angina frequency domain to generate an angina frequency composite score. In the overall sample (58.8±11.7 years old, 52.6% female), 42.8% had obesity, and 71.5% had CP, with an angina frequency composite score (SD) score of 76.4 (22.1). Compared with individuals without obesity, individuals with obesity had a higher prevalence (77.6% versus 67%, P P =0.02). Obesity was independently associated with CP occurrence (odds ratio [OR], 1.7 [95% CI, 1–2.9], P =0.04). Obesity's connection with CP was only in men: men with obesity had more frequent CP (angina frequency composite score, 75.8 [SD, 20.1] versus 82.1 [SD, 19.9], P =0.002) and more prevalent CP (79.5% versus 58.2%, P P =0.03) was independently associated with CP and partly mediated the association between obesity and CP. Conclusions: Obesity and depressive symptoms were independently associated with CP in individuals with nonobstructive coronary artery disease, particularly in men, and depressive symptoms partly mediated this association.

Background: Literature suggests a bidirectional association between advanced hepatic fibrosis (AHF) and coronary artery disease (CAD). We evaluated the association of AHF with immune activation, systemic inflammation, and adverse outcomes in patients with CAD. Methods and Results: A fibrosis‐4 index cutoff value ≥2.67 was used to define AHF. Circulating levels of soluble urokinase plasminogen activator receptor and hsCRP (high‐sensitivity C‐reactive protein) were measured as markers for immune activation and systemic inflammation, respectively. The relationship of AHF with soluble urokinase plasminogen activator receptor, hsCRP, and adverse cardiovascular outcomes was evaluated. Among 3406 participants with CAD, 479 had AHF. Participants with AHF were older; were less likely to be Black individuals; and had a lower body mass index, worse renal function, and a prior history of heart failure. In multivariable linear regression models adjusted for clinical and demographic confounders, participants with AHF had 15.6% higher soluble urokinase plasminogen activator receptor and 24.0% higher hsCRP levels. They were more likely to experience the following adverse outcomes: all‐cause death (adjusted hazard ratio [HR], 1.57 ([95% CI, 1.29–1.92]; P P =0.003). Mediation analysis showed that 47.0% (95% CI, 13.6%–81.2%]; P =0.006) of the indirect effect of AHF on cardiovascular death was mediated by circulating soluble urokinase plasminogen activator receptor levels. Conclusions: AHF is independently associated with immune activation, systemic inflammation, and adverse cardiovascular outcomes in patients with CAD. The association of AHF with adverse outcomes is partly mediated by immune activation, and targeting this pathway may help reduce the residual risk in patients with CAD.

Background: The survival benefit of revascularization of chronic total occlusion (CTO) of the coronary arteries remains a subject of controversy. We measured high sensitivity troponin‐I (hsTn‐I) levels as an estimate of myocardial ischemia in patients with stable coronary artery disease, with the hypothesis that (1) patients with CTO have higher levels of hsTn‐I than patients without CTO, (2) hsTn‐I levels will predict adverse cardiovascular events in patients with CTO, and (3) patients with elevated hsTn‐I levels will have a survival benefit from CTO revascularization. Methods and Results: In 428 patients with stable coronary artery disease and CTO undergoing coronary angiography, adverse event rates were investigated. Cox proportional hazards models and Fine and Gray subdistribution hazard models were performed to determine the association between hsTn‐I level and incident event rates in patients with CTO. HsTn‐I levels were higher in patients with compared with those without CTO (median 6.7 versus 5.6 ng/L, P =0.002). An elevated hsTn‐I level was associated with higher adverse event rates (adjusted all‐cause mortality hazard ratio, 1.19 [95% CI, 1.08–1.32]; P =0.030) for every doubling of hsTn‐I level. CTO revascularization was performed in 28.3% of patients. In patients with a high (>median) hsTn‐I level, CTO revascularization was associated with substantially lower all‐cause mortality (adjusted hazard ratio, 0.26 [95% CI, 0.08–0.88]; P =0.030) compared with those who did not undergo revascularization. In patients with a low ( < median) hsTn‐I level, event rates were similar in those with and without CTO revascularization. Conclusions: HsTn‐I levels may help identify individuals who benefit from CTO revascularization.

Introduction: Cardiac allograft vasculopathy (CAV) limits long‐term survival in heart transplant (HTx) recipients. The use of biomarkers in CAV surveillance has been studied, but none are used in clinical practice. The predictive value of high‐sensitivity troponin I (hsTnI) has not been extensively investigated in HTx recipients.Methods: HTx patients undergoing surveillance coronary angiograms and enrolled in the Emory Cardiovascular Biobank had plasma hsTnI measured. CAV grade was assessed using ISHLT nomenclature. Multivariable cumulative link mixed modeling was performed to determine association between hsTnI level and CAV grade. Patients were followed for adverse outcomes over a median 10‐year period. Kaplan‐Meier survival analysis and Cox proportional hazard modeling were performed.Results: Three hundred and seventy‐two angiograms were analyzed in 156 patients at a median 8.9 years after transplant. hsTnI levels were positively correlated with concurrent CAV grade after adjustment for age, age at transplant, sex, BMI, hypertension, diabetes, hyperlipidemia, estimated glomerular filtration rate, and history of acute cellular rejection (p = .016). In an adjusted Cox proportional hazard model, initial hsTnI level above the median (4.9 pg/mL) remained a predictor of re‐transplantation or death (hazard ratio 1.82; 95% confidence interval 1.16–2.90; p = .01).Conclusion: An elevated hsTnI level reflects severity of CAV and is associated with poor long‐term outcomes in patients with HTx.

Background: Women have higher circulating levels of soluble urokinase‐type plasminogen activator receptor (suPAR), and elevated suPAR is associated with cardiovascular risk. The independent association of sex with suPAR and the impact of sex on its association with cardiovascular risk are unknown. Methods and Results: Plasma suPAR was measured using ELISA in 2 cohorts of 666 asymptomatic individuals (49 years, 65% women) and 4184 patients with coronary artery disease (63 years, 37% women). Independent association of sex with suPAR was studied using linear regression models adjusted for demographics, risk factors, and visceral adiposity in asymptomatic participants. Impact of sex on association of suPAR with all‐cause mortality was studied in patients with coronary artery disease using multivariable‐adjusted Cox models. Sex‐specific suPAR cutoffs for predicting all‐cause mortality were calculated. Asymptomatic women had 10% higher suPAR compared with men after adjusting for confounders, and visceral adiposity partly accounted for this association. Over a median follow‐up of 5.2 years, 795 deaths were recorded in patients with coronary artery disease. Log ₂ ‐transformed suPAR was independently associated with mortality (hazard ratio per 1‐SD 1.72, 95% CI 1.60–1.85) and an interaction with sex was noted ( P =0.005). Association of suPAR with mortality was slightly weaker in women (hazard ratio 1.61, 95% CI 1.41–1.83) compared with men (hazard ratio 1.83, 95% CI 1.67–2.00). However, using sex‐specific suPAR cut‐offs (4392 pg/mL for women and 3187 pg/mL for men), a similar mortality incidence was observed for both sexes (38.5% and 35.5%, respectively, P =0.3). Conclusions: Women have 10% higher plasma suPAR levels compared with men. Elevated sex‐specific plasma suPAR levels are equally predictive of risk of adverse events in both sexes.