Serum Homocysteine in Relation to Mortality and Morbidity From Coronary Heart Disease

Abstract

Background-Elevated serum total homocysteine (tHcy) is an established risk factor for cardiovascular disease (CVD), especially in men. However, there are few prospective population studies on female cohorts, and none of these has been longer than 13 years. Gothenburg began in 1968Gothenburg began in /1969, at which time a representative population-based cohort of women aged 38, 46, 50, 54, and 60 years was recruited. The present cohort is a prospective follow-up of 1368 women in the original cohort for whom blood samples were stored and who were free of previous acute myocardial infarction (AMI) at the 1968/1969 baseline. Homocysteine was analyzed in 2001 with frozen serum from the baseline study and related to AMI incidence and mortality during 24 years of follow-up. Cox regression analyses were used with adjustment for age, traditional risk factors, and tHcy modifiers. For the fifth tHcy quintile, relative risk was 1.86 (95% CI 1.06 to 3.26) for AMI and 5.14 (95% CI 2.22 to 11.92) for death due to AMI. Age-standardized Kaplan-Meier plots for the fifth tHcy quintile versus others showed significant differences both for AMI and for death due to AMI that were apparent after 15 years of follow-up. Conclusions-Homocysteine in middle-aged women is an independent risk factor for myocardial infarction and in particular mortality due to myocardial infarction. The study illustrates that long-term prospective studies might be necessary to show effects of homocysteine levels on AMI morbidity and mortality in women. Key Words: homocysteine Ⅲ women Ⅲ myocardial infarction S erum total homocysteine (tHcy) is a well-known risk factor for coronary heart disease in men, whereas relatively fewer studies have demonstrated such associations prospectively in women. Alfthan et al 1 followed a female Finnish cohort for 9 years and showed no association between tHcy and either acute myocardial infarction (AMI) or stroke, nor did Folsom et al 2 after 3.3 years of follow-up. In contrast, Ridker et al, 3 in a nested case-control study in the United States, demonstrated that tHcy was a risk factor for cardiovascular disease (CVD) among postmenopausal women after 3 years of follow-up. Morris et al 4 found a significant relation between tHcy and heart attack or stroke, especially in postmenopausal women, in their (NHANES III) study. Knekt et al,5 with the longest reported follow-up of 13 years, found a significant relation between tHcy and coronary artery disease in women with prevalent heart disease at baseline but not among women free of heart disease at baseline. Recent systematic reviews indicate that most previous research has been based on relatively short-term follow-up, from 1.4 to 13 years. 6,7 There has been some indication that elevated tHcy levels are more predictive of fatal than nonfatal vascular events 8,9 and more predictive of hospitalization in older versus younger populations, 10 although this is not yet clearly shown for women. Methods and Results-The Population Study of Women inHomocysteine is an amino acid involved in...

Homocysteine, 5,10-Methylenetetrahydrofolate Reductase 677C>T Polymorphism, Nutrient Intake, and Incident Cardiovascular Disease in 24 968 Initially Healthy Women

“…Taken together, these findings do not support a strong role for either homocysteine or the MTHFR 677CϾT polymorphism as etiologic cardiovascular risk factors in healthy women. The magnitude of the association between homocysteine and incident CVD in this study was consistent with a small case-control analysis in these women (25 ) and a recent metaanalysis of observational studies that included predominantly men (2 ), although the findings differ from those of a 24-year prospective study in healthy women that found significant associations with myocardial infarction (26 ). Although case-control studies have tended to report strong associations between homocysteine and CVD, many prospective studies have shown weaker or no associations (1,2 ).…”

Hydrogen sulphide-related thiol metabolism and nutrigenetics in relation to hypertension in an elderly population

“…The contribution of this haem-containing enzyme to H 2 S generation likely decreases under conditions of hyperhomocysteinaemia; gasotransmitter synthesis is relatively insensitive to Hcy, indicating that cystathionine c-lyase is largely responsible for enhancing H 2 S generation under conditions of hyperhomocysteinaemia. These findings, it has been suggested, point to an important new role for cystathionine c-lyase in the thiol metabolome and Hcy management (Singh et al 2009) and, as the present data indicate, in contributing to a significant clinical phenotype associated with substantial rates of morbidity and mortality (Kearney et al 2005;Reynolds et al 2007;Inoue et al 2007;Elliott 2005;Schultz et al 2007;Paoletti et al 2006;Parnetti et al 2004;Zylberstein et al 2004;Boushey et al 1995;Zhou et al 2001;Sutton-Tyrell et al 1997;Nygard et al 1997). Since H 2 S is highly reactive and has long been considered as toxic, its impact on various tissues is well characterised, but with recent advances in our knowledge, implicating H 2 S in Alzheimer's disease, epilepsy and stroke (Gadalla and Snyder 2010;Gupta et al 2010) as well as hypertension, future development of drugs specifically modulating H 2 S levels is likely to prove beneficial (Gupta et al 2010).…”

“…It is well recognised that Hcy acts as an independent risk factor for CVD, including hypertension (Parnetti et al 2004;Zylberstein et al 2004;Boushey et al 1995;Zhou et al 2001;Sutton-Tyrell et al 1997;Nygard et al 1997). In this context, much work has been published in relation to the role of folic acid nutrition and genetics in lowering Hcy, including the beneficial effects of vitamins B 12 and B 6 (Lucock 2006).…”

Homocysteine (Hcy) Follow-Up Study

“…These differences both for AMI and for death due to AMI were apparent after 15 years of follow-up. 18 In our study women were not affected at all from high Hcy concentrations -in any of the parameters that were studied (survival, chest pain, CVA). In a study that examined Hcy concentration in patients with coronary artery disease it was found that patients with coronary artery ectasia and coronary artery disease had higher Hcy concentrations than controls.…”