ABSTRACT
Objectives: The 2018 and 2019 U.S. guidelines for the management of cholesterol and primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend consideration of cardiovascular risk-enhancing factors (REFs), including South Asian ancestry, to refine ASCVD risk estimation. However, the associations of REFs with atherosclerosis are unclear in South Asian American adults, who have a disproportionately elevated premature coronary heart disease risk. In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we investigated associations of individual REFs, or the number of REFs, with coronary artery calcium (CAC). Methods: Using baseline and follow-up data from MASALA, we evaluated the association of REFs (family history of ASCVD, low-density lipoprotein cholesterol ≥160 mg/dL, triglycerides ≥175 mg/dL, lipoprotein(a) >50 mg/dL, high-sensitivity C-reactive protein [hsCRP] ≥2.0 mg/dL, ankle-brachial index <0.9, chronic kidney disease, metabolic syndrome), individually and combined, with baseline prevalent CAC, any CAC progression (including incident CAC and CAC progression), and annual CAC progression rates using multivariable logistic regression and generalized linear models. Results: Among 866 adults, mean age was 55 [SD 9] years and 47% were female. There were no significant associations of REFs with baseline prevalent CAC or any CAC progression (incident CAC and CAC progression at Exam 2) after adjustment. Among the 56% of participants who had any CAC progression, having 3+ REFs was associated with a significantly higher annual CAC progression rate (adjusted rate ratio [aRR] 1.94, 95% CI 1.39-2.72) vs. having 0 REFs. The annual CAC progression rate was 20% higher per additional REF (aRR 1.20, 95% CI 1.09-1.32). Findings were similar after excluding statin users, and among those with low 10-year ASCVD risk (<5%). Conclusions: Among South Asian American adults, we found no association of REFs with prevalent CAC at baseline or having any CAC progression. Among those with any CAC progression, a higher number of REFs was associated with higher annual CAC progression rates.
ABSTRACT
Stent thrombosis (ST) is a rare but devastating complication after percutaneous coronary intervention. Newer generation drug-eluting stents (DES) and newer antiplatelet therapies have been shown to decrease the incidence of ST, but we continue to observe ST-segment elevation myocardial infarction (STEMI) due to ST in contemporary practice. A retrospective analysis of 527 patients who presented with STEMI was performed; 57 patients (11%) with angiographically confirmed ST were compared with the patients with STEMI due to de novo lesion. The type of previous stent, the timing of ST, and the use of antiplatelet therapy were reviewed in patients with ST. Patients with ST had higher prevalence of comorbid conditions, such as hypertension, diabetes mellitus, and coronary artery disease, and had lower left ventricular ejection fraction (37 ± 5 vs. 44 ± 16%, p = 0.0011). There was no difference in in-hospital mortality (2 vs. 4%, p = 0.7082). ST was seen most commonly as "very late" (56%), and with previous second-generation DES (40%). Eighty-two percent of patients among early ST, compared with 22% of patients with very late ST were on dual antiplatelet therapy (DAPT). In 12% of patients, ST happened after DAPT was stopped by physician for procedures. ST is seen in a variety of clinical settings with the most common presentation being very late ST and in second-generation DES, which most likely represent the growing population with previous second-generation stents.
ABSTRACT
Activin A is a potent growth and differentiation factor whose synthesis and bioactivity are tightly regulated. Both follistatin binding and inhibin subunit heterodimerization block access to the activin receptor and/or receptor activation. We postulated that the activin-beta(C) subunit provides another mechanism regulating activin bioactivity. To test our hypothesis, we examined the biological effects of activin C and produced mice that overexpress activin-beta(C). Activin C reduced activin A bioactivity in vitro; in LNCaP cells, activin C abrogated both activin A-induced Smad signaling and growth inhibition, and in LbetaT2 cells, activin C antagonized activin A-mediated activity of an follicle-stimulating hormone-beta promoter. Transgenic mice that overexpress activin-betaC exhibited disease in testis, liver, and prostate. Male infertility was caused by both reduced sperm production and impaired sperm motility. The livers of the transgenic mice were enlarged because of an imbalance between hepatocyte proliferation and apoptosis. Transgenic prostates showed evidence of hypertrophy and epithelial cell hyperplasia. Additionally, there was decreased evidence of nuclear Smad-2 localization in the testis, liver, and prostate, indicating that overexpression of activin-beta(C) antagonized Smad signaling in vivo. Underlying the significance of these findings, human testis, liver, and prostate cancers expressed increased activin-betaC immunoreactivity. This study provides evidence that activin-beta(C) is an antagonist of activin A and supplies an impetus to examine its role in development and disease.
