Objective-Asymmetrical dimethylarginine (ADMA) reduces nitric oxide by inhibiting nitric oxide synthase is associated with cardiovascular disease (CVD). Our study examined the association of ADMA with CVD prospectively in a healthy population-based cohort of women. Methods and Results-We measured baseline ADMA of 880 women in the Population Study of Women in Gothenburg using high-performance liquid chromatography. After adjustment for traditional risk factors, creatinine clearance, and homocysteine using Cox models, the HR (95% CI in parentheses) of CVD end points at 24 years for a 0.15 mol/L (1 SD) increase in ADMA were: all-cause mortality 1.12 (0.96, 1.32), fatal CVD 1.30 (1.04, 1.62), total CVD events 1.29 (1.09, 1.53). The top quintile (ADMA Ն0.71 mol/L) compared with the bottom four-fifths, conferred a cumulative risk 22 versus 14%, relative risk 1.75 (95% CI 1.18, 2.59) and population attributable risk 12.7% of total CVD events, and further identified individuals who are at higher than expected risk based on the SCORE and Framingham systems. Conclusions-A 0.15 mol/L increase in baseline ADMA levels is associated with approximately 30% increase in incident cardiovascular risk at 24 years in women after adjustment. ADMA levels Ն0.71 mol/L enhances CVD risk assessment in women. Key Words: asymmetrical dimethylarginine Ⅲ cardiovascular diseases Ⅲ myocardial infarction Ⅲ stroke Ⅲ women A symmetrical dimethylarginine (ADMA) has been proposed as a novel risk marker for cardiovascular disease 1-4 beause of its possible role in endothelial dysfunction, 5-7 a process thought to be pivotal in the development of arteriosclerosis. 8 Both symmetrical dimethylarginine (SDMA) and ADMA are structural analogues of the amino acid L-arginine, the substrate for the synthesis of nitric oxide by the enzyme nitric oxide synthase. 9 ADMA is an endogenous competitive inhibitor of nitric oxide synthase. 1,5 Therefore, raised levels of ADMA lead to reduced nitric acid production and hence impair endothelial function.Both ADMA and SDMA are excreted by the kidneys. Most of endogenous ADMA is broken down by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) into dimethylamine and citrulline, which are also excreted through the kidneys. Hence, ADMA, as well as SDMA, accumulates in patients with renal failure. 5 However, SDMA does not inhibit nitric oxide synthase, nor is it a substrate for DDAH. Furthermore, it has been thought that the effect of homocysteine on endothelial function may be mediated through ADMA 10,11 because of the fact that homocysteine may inhibit DDAH, leading to increased ADMA levels, and hence reduced nitric oxide production.ADMA has been reported to be raised in the presence of other cardiovascular risk factors, as well as in several disease states. These cardiovascular risk factors include traditional risk factors such as blood pressure, 12-14 serum cholesterol, 6 serum triglycerides, 15 gestational diabetes, 16 insulin resistance, 17 smoking, and nontraditional risk markers such as homocysteine, 11,18,...

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...

Longitudinal studies in elderly populations provide important data on changes during the ageing process. However, participation rates decline for a number of reasons and generalisations should be made with care. Moreover, including home visits in the protocol can both increase participation and reduce participation bias in elderly cohorts.

Several cardiovascular risk factors related to lifestyle have improved in middle-aged women from the 1960s until today. Most of the positive trends are observed in women with both low and high physical activity.