Elevated plasma cystathionine is associated with increased risk of mortality among patients with suspected or established coronary heart disease

Indu Dhar; Vegard Lysne; Gard F T Svingen; Per M Ueland; Jesse F Gregory; Kaare H Bønaa; Ottar K Nygård

doi:10.1093/ajcn/nqy391

Elevated plasma cystathionine is associated with increased risk of mortality among patients with suspected or established coronary heart disease

Am J Clin Nutr. 2019 Jun 1;109(6):1546-1554. doi: 10.1093/ajcn/nqy391.

Authors

Indu Dhar^{1

2}, Vegard Lysne¹, Gard F T Svingen³, Per M Ueland^{1

4}, Jesse F Gregory⁵, Kaare H Bønaa⁶, Ottar K Nygård^{1

2

3}

Affiliations

¹ Department of Clinical Science, KG Jebsen Centre for Diabetes Research, University of Bergen, Bergen, Norway.
² KG Jebsen Centre for Diabetes Research, University of Bergen, Bergen, Norway.
³ Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
⁴ Bevital AS, Bergen, Norway.
⁵ Food Science and Human Nutrition Department, University of Florida, Gainesville, FL.
⁶ Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

PMID: 31005968
DOI: 10.1093/ajcn/nqy391

Abstract

Background: Elevated circulating cystathionine levels are related to atherosclerotic cardiovascular disease, a leading cause of death globally.

Objective: We investigated whether plasma cystathionine was associated with mortality in patients with suspected or established coronary heart disease (CHD).

Methods: Data from 2 independent cohorts of patients with suspected stable angina pectoris (SAP) (3033 patients; median 10.7 y follow-up; 648 deaths) or acute myocardial infarction (AMI) (3670 patients; median 7.0 y follow-up; 758 deaths) were included. Hazard ratios with 95% CIs per SD increment of log-transformed cystathionine were calculated using Cox regression modeling. Endpoint data was obtained from a national health registry.

Results: Among patients with SAP, there was a positive association between plasma cystathionine and death (age- and sex-adjusted HRs [95% CI] per SD: 1.23 [1.14, 1.32], 1.29 [1.16, 1.44], and 1.17 [1.05, 1.29] for total, cardiovascular, and noncardiovascular mortality, respectively). Corresponding risk estimates were 1.28 (1.19, 1.37) for all-cause, 1.33 (1.22, 1.45) for cardiovascular, and 1.19 (1.06, 1.34) for noncardiovascular death among AMI patients. In both cohorts, estimates were slightly attenuated after multivariate adjustments for established CHD risk factors. Subgroup analyses showed that the relation between cystathionine and all-cause mortality in SAP patients was stronger among nonsmokers and those with lower plasma concentration of pyridoxal-5'-phosphate (P-interaction ≤ 0.01 for both).

Conclusions: Elevated plasma cystathionine is associated with both cardiovascular and noncardiovascular mortality among patients with suspected or established CHD. The joint risk associations of high plasma cystathionine with lifestyle factors and impaired vitamin B-6 status on mortality need further investigation. This trial was registered at clinicaltrials.gov as NCT00354081 and NCT00266487.

Keywords: B-vitamins; coronary heart disease; cystathionine; mortality; risk factors; survival.

Publication types

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

MeSH terms

Adult
Aged
Angina, Stable / blood
Angina, Stable / mortality*
Biomarkers / blood
Cohort Studies
Cystathionine / blood*
Female
Follow-Up Studies
Humans
Male
Middle Aged
Myocardial Infarction / blood
Myocardial Infarction / mortality*
Proportional Hazards Models
Risk Factors
Vitamin B 6 / blood

Substances

Biomarkers
Cystathionine
Vitamin B 6

Associated data

ClinicalTrials.gov/NCT00354081
ClinicalTrials.gov/NCT00266487