Aim: The metabolic syndrome is associated with increased cardiovascular risk. Elevated plasma homocysteine may cause or result from insulin resistance, and may indicate vascular risk or be actively involved in atherogenesis. The aim of the study was to investigate the relationship between homocysteine, the metabolic syndrome and the incidence of cardiovascular events in patients with manifest vascular disease.
Methods: A cohort of 2169 patients with manifest vascular disease was followed for a mean period of 2.8 years. Plasma homocysteine was measured at baseline. Metabolic syndrome was defined by NCEP criteria.
Results: Homocysteine levels were higher in metabolic syndrome patients compared to patients without the metabolic syndrome (14.9±0.2 v 14.1±0.2 μmol/l; p = 0.002) and increased with the presence of its components (from 0 to 5) (12.7 to 15.9 μmol/l; p<0.001). During follow-up, 52 strokes, 67 myocardial infarctions, 5 fatal ruptures of aortic aneurysms and 53 vascular deaths occurred. Patients without the metabolic syndrome and homocysteine levels in the highest tertile had increased risk for events (HR 1.9; 95% CI 1.0 to 3.5) compared to patients without the metabolic syndrome and homocysteine levels in the lowest tertile. The presence of the metabolic syndrome increased the risk (HR 2.2; 95% CI 1.2 to 4.2), but elevated homocysteine levels further increased the risk only marginally (2.5; 95% CI 1.4 to 4.6).
Conclusions: Metabolic syndrome patients have elevated homocysteine levels, but these higher levels are not associated with an increased risk for new cardiovascular events. In contrast, elevated homocysteine levels confer increased risk in patients without the metabolic syndrome.
- 95% CI, 95% confidence intervals
- HR, hazard ratio
- SD, standard deviation
- cardiovascular disease
- metabolic syndrome
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Published Online First 4 September 2006
↵* Participants of the SMART study group (for coordination and supervision of the cohort) are: A Algra, MD, PhD; Y van der Graaf, MD, PhD; DE Grobbee, MD, PhD; GEHM Rutten, MD, PhD, Julius Centre for Health Sciences and Primary Care; FLJ Visseren, MD, PhD, Department of Internal Medicine; BC Eikelboom, MD, PhD; FL Moll, MD, PhD, Department of Vascular Surgery; LJ Kappelle, MD, PhD, Department of Neurology; HA Koomans MD, PhD, Department of Nephrology; WPThM Mali, MD, PhD, Department of Radiology; PA Doevendans, MD, PhD, Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
No financial disclosure statement is needed.
Competing interests: None.