No abstract

). Plasma total homocysteine levels and prognosis in patients with previous premature myocardial infarction: a 10-year follow-up study. J Intern Med 2003; 253: 284-292.Objectives. To explore plasma total homocysteine (tHcy) as a predictor of long-term prognosis after premature myocardial infarction (MI). Design. Prospective cohort study. Settings. Akershus University Hospital. Subjects. A total of 247 patients (193 men and 54 women) in stable clinical phase after premature MI (males: first MI at age £55; females £60). Main outcome measures. The primary end-point was total mortality and the secondary end-point was cardiac death. The third end-point was major cardiac events: a combination of cardiac death, MI and cardiac arrest.Results. After 10 years, 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients. The relative risk for death of all causes increased 1.43 (95% CI, 1.08-1.88) per tHcy quartile (P for trend ¼ 0.01), and was only modestly reduced after adjustment for age, ejection fraction, total cholesterol, C-reactive protein, fibrinogen, smoking and hypertension to 1.37 (95% CI, 1.04-1.80) (P for trend ¼ 0.03). Similar results were observed when cardiac death was used as the end-point, but we observed no association between tHcy and the endpoint major cardiac event. Conclusions. Total homocysteine was an independent predictor of total and cardiac mortality in stable patients following premature MI. tHcy had no effect on major cardiac event in contrast to most other risk factors in this study. Thus, the mechanism(s) underlying the effects of homocysteine on coronary heart disease may differ from other risk factors.

Two hundred and thirty‐five survivors of myocardial infarction (MI) were compared to 384 controls with respect to distribution of genotypes and gene frequencies in the A1166C polymorphism at the angiotensin II type 1 receptor (AT1R) locus. No differences in allele frequencies or genotype distribution were observed when all patients were compared with all controls. When comparing CC homozygotes with the combined group of CA heterozygotes and AA homozygotes (CA/AA), a difference in borderline significance between the MI group and controls was observed (p = 0.05). In males alone, this difference was much more pronounced because of the larger proportion of males with the CC genotype in MI cases than in male controls (p = 0.01). No significant differences were observed between female cases and controls. No interaction between the insertion/deletion (I/D) polymorphism at the angiotensin I‐converting enzyme (ACE) locus and the polymorphism at the AT1R locus was detected. When subdividing the subjects into a “low‐risk” and a “high‐risk” group, based on levels of apolipoprotein B (apoB) and body mass index (BMI), and whether or not the person used lipid‐lowering drugs, the frequency of CC homozygotes in male cases of the “low‐risk” group differed significantly compared to the frequency in male controls of the “low‐risk” group (p < 0.001). No differences were observed in females, but the number of “low‐risk” group female cases was low (n = 3). Thus, CC homozygosity appears to be associated with MI in Norwegian males, especially among those with a “low‐risk” phenotype.

Abstract. Retterstol L, Kierulf P, Pedersen JC, Bohn M, Bakken A, Erikssen J, Berg K (Institute of Medical Genetics, University of Oslo and Ulleva Êl University Hospital, Oslo; and Central Hospital of Akershus, Nordbyhagen, Norway). Plasma ®brinogen level and long-term prognosis in Norwegian middle-aged patients with previous myocardial infarction. A 10 years follow-up study. J Intern Med 2001; 249: 511±518.Objectives. To investigate the prognostic value of plasma ®brinogen level amongst middle-aged survivors of myocardial infarction (MI). Design. Prospective cohort study. Settings. Determination of ®brinogen and other prognostic variables in MI patients recruited in a presumably stable phase of coronary heart disease (CHD). Subjects. A total of 247 middle-aged CHD patients (54 women and 193 men) who had their ®rst MI at age £60 (women) or £55 (men) were recruited at least 3 months after (mean 2.1 years) the most recent MI.Main outcome measures. The primary endpoint was total mortality, and the secondary endpoint was cardiac deaths. The tertiary endpoint was major cardiac events (cardiac death, MI and cardiac arrest). Results. During a follow-up period of 10 years a total of 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients. After adjusting for age, ejection fraction (EF), total serum cholesterol (TC), smoking and hypertension, patients in the top quartile of ®brinogen (³4.0 g L ±1 ) had a relative risk (RR) of 1.8 (95% CI 1.0±3.6) (P 0.07) for death of all causes. The top quartile of ®brinogen was a stronger predictor of cardiac death; RR 2.2 (95% CI 1.1±4.4) (P 0.03), whilst the effect on the endpoint major cardiac event was not signi®cant; RR 1.1 (95% CI 0.6±1.9) (P 0.69). Conclusions. A plasma ®brinogen level in the top quartile predicted cardiac death in middle-aged patients who had suffered MI.

Bøhn M, Bakken A, Erikssen J, Berg K. Xbal polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI). Clin Genet 1993: 44: 241–248. © Munksgaard, 1993 High levels of low density lipoprotein (LDL) and its apolipoprotein B (apoB) are risk factors for atherosclerosis and myocardial infarction (MI). There is rich genetic polymorphism in apoB, first detected as the Ag allotypes of LDL, but today mostly examined at the DNA level. Genes contribute to the population variation in LDL and apoB levels and alleles in polymorphisms at the apoB locus are candidate genes with respect to control of lipid levels and susceptibility to atherosclerosis and MI. The Xbal polymorphism at the apoB locus, which involves the third base of threonin codon 2488 (ACC→ACT) without changing the amino acid sequence was examined in a case‐control study comprising 238 survivors of myocardial infarction (MI) and 621 controls. In univariate analysis, frequencies of genotypes in this polymorphism were not statistically different between patients and controls of either sex. However, in multivariate logistic regression analysis, the odds ratio X ‐ X ‐ homozygotes (homozygotes for absence of restriction site) for having MI compared to the pooled group of heterozygotes and X + X + homozygotes (homozygotes for presence of restriction site) was 2.16 (p = 0.007), after adjustments for age, sex, and levels of apoB, high density lipoprotein (HDL) cholesterol (HDLC) and Lp(a) lipoprotein. It appeared that heterozygotes do not have increased risk, compared to the X + X + homozygotes. Stratification according to low or high levels of apoB, HDLC and Lp(a) lipoprotein, showed that the X ‐ X ‐ genotype was more common in patients than controls, in all subgroups. We conclude that the X ‐ allele in double (but not in single) dose most probably increases the risk of MI. The increased risk is apparently not conferred by higher levels of total cholesterol, LDL or apoB, but through some variable or mechanism not closely related to traditional risk factors.