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

Wenjie Yin; Fengjuan Li; Xin Tan; Huimin Wang; Wenxi Jiang; Xue Wang; Sijin Li; Yanbo Zhang; Qinghua Han; Yuan Wang; Jie Du

doi:10.1093/ajh/hpab105

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

Am J Hypertens. 2021 Nov 20;34(11):1209-1216. doi: 10.1093/ajh/hpab105.

Authors

Wenjie Yin^{1

2

3

4}, Fengjuan Li^{3

4}, Xin Tan^{3

4}, Huimin Wang^{1

3

4}, Wenxi Jiang^{3

4}, Xue Wang^{3

4}, Sijin Li^{2

5}, Yanbo Zhang⁶, Qinghua Han², Yuan Wang^{3

4}, Jie Du^{1

3

4

5}

Affiliations

¹ Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi Province, China.
² The First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
³ Beijing Collaborative Innovation Center for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁴ Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
⁵ Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, Shanxi Province, China.
⁶ Department of Health Statistics, Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province, China.

PMID: 34232291
DOI: 10.1093/ajh/hpab105

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.

Keywords: biomarker; blood pressure; cardiovascular; ceramide; hypertension; risk score.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Cardiovascular Diseases* / diagnosis
Cardiovascular Diseases* / epidemiology
Ceramides / analysis
Female
Heart Disease Risk Factors
Humans
Hypertension* / complications
Hypertension* / diagnosis
Hypertension* / drug therapy
Male
Middle Aged
Risk Factors

Substances

Ceramides

Associated data

ClinicalTrials.gov/NCT03708601