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The Hordaland Homocysteine Study

Eha Nurk, MD; Grethe S. Tell, PhD; Stein Emil Vollset, MD, DrPH; Ottar Nygård, MD; Helga Refsum, MD; Per M. Ueland, MD

Arch Intern Med. 2002;162:1374-1381.

Background  Elevated total plasma homocysteine (tHcy) level is a risk factor for occlusive disease in the coronary, cerebral, and peripheral vessels and is related to several lifestyle factors associated with cardiovascular disease (CVD).

Objective  To examine the association of a single tHcy measurement on subsequent hospitalizations due to CVD.

Methods  A population-based prospective cohort study was conducted from April 1, 1992, to May 31, 1998 (mean follow-up, 5.3 years) in western Norway. The study included 17 361 individuals aged 40 to 42 or 65 to 67 years at baseline. Main outcome measure was CVD as the main hospital discharge diagnosis or coronary revascularization procedures (denoted "CVD hospitalizations") during follow-up (n = 1275).

Results  At baseline, participants with preexisting CVD had higher mean tHcy values than individuals without CVD. Risk of CVD hospitalizations increased significantly with increasing baseline tHcy only in the oldest age group. Here, multiple risk factor–adjusted hospitalization rate ratios in 5 tHcy categories (<9, 9-11.9, 12-14.9, 15-19.9, and 20 µmol/L [to convert tHcy to milligrams per liter, divide by 7.397]) were as follows: 1 (reference level), 1.00, 1.34, 1.67, and 1.94, respectively (P for trend <.001). The relation between tHcy level and CVD hospitalizations was significantly stronger among individuals with preexisting CVD than those without (hospitalization rate ratio per 5-µmol/L tHcy increment, 1.29 vs 1.10; P for interaction, .02).

Conclusions  Plasma tHcy level is a strong predictor of CVD hospitalizations only in elderly individuals, and especially among those with preexisting CVD. Our findings are compatible with the theory that tHcy interacts with conventional CVD risk factors to provoke the acute event of CVD.

From the Department of Public Health and Primary Health Care (Drs Nurk, Tell, and Vollset), Institute of Medicine (Dr Nygård), and Department of Pharmacology (Drs Refsum and Ueland) and Locus for Homocysteine and Related Vitamins (Drs Nurk, Tell, Vollset, Nygård, and Ueland), University of Bergen, Bergen, Norway.

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