Plasma Ceramides and Cardiovascular Events in Hypertensive Patients at High Cardiovascular Risk

Abstract

Background: Plasma ceramides (Cer) have been used to evaluate risk of cardiovascular (CV) events in patients with coronary heart disease. We investigated the performance of ceramides and ceramide score (CERT) in hypertensive patients at high CV risk. Methods: Seven ceramides were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry in 920 essential hypertension patients at high CV risk, who visited Beijing Anzhen Hospital from September 2016 to September 2018 (median age: 49 years, 562 males). All patients were followed up for major adverse cardiovascular events (MACE), which included incident acute coronary syndrome, heart failure, stroke, and CV death. Results: During mean 2.3-year follow-up, 71 patients experienced MACE. Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0) were highly significant in predicting MACE [multiadjusted hazard ratios (95% confidence interval, CI) per SD were 1.76 (1.34-2.30), 0.55 (0.41-0.73), and 0.66 (0.47-0.92), respectively]. Compared with traditional variables (comprising presence of CV risk factors, hypertension-mediated organ damage, and comorbidities), a novel CERT for hypertensive patients (CERT-HBP), composed of Cer(d18:1/16:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) and Cer(d18:1/22:0), respectively, increased the C-statistic from 0.751 (95% CI, 0.697-0.806) to 0.791 (95% CI, 0.737-0.845), P = 0.010. Net reclassification improvement and integrated discrimination improvement were 0.648 (95% CI, 0.421-0.885, P < 0.001) and 0.046 (95% CI, 0.025-0.068, P < 0.001), respectively. Conclusions: A ceramide-based CERT-HBP was established to evaluate risk of MACE in hypertensive patients at high CV risk. This may improve identification of high-risk patients requiring increased attention and aggressive therapy. Clinical trials registration: Trial Number NCT03708601.