Risk of myocardial infarction in relation to plasma levels of homocysteine and inflammation-sensitive proteins: a long-term nested case-control study.
ABSTRACT Several studies have found that the homocysteine plasma level is associated with cardiovascular disease. The authors previously described a relationship between concentrations of fibrinogen and other inflammation-sensitive plasma proteins, namely, alpha1-antitrypsin, ceruloplasmin, haptoglobin, and orosomucoid (alpha1-acid glucoprotein) and the incidence of myocardial infarction (MI). Whether levels of these proteins are related to homocysteine has not been clarified. The aim of this study was to investigate whether a supposed relationship between homocysteine in plasma and the occurrence of MI is modified by these inflammation-sensitive proteins. A nested case-control study was designed, comprising 241 cases of MI, with a mean age of 48 years at baseline, and 241 controls matched for age, month of examination, and duration of follow-up. The mean homocysteine concentration did not differ between cases and controls and there was no association between the baseline homocysteine level and the time lapse before the occurrence of the MI. For the cases, there was no correlation between homocysteine and any of the measured proteins, but for the controls, homocysteine was weakly but significantly negatively correlated to haptoglobin and ceruloplasmin and slightly positively correlated to albumin. For the separated groups of cases and controls there was no association between the number of inflammation-sensitive proteins in the top quartiles and homocysteine concentration. In this population-based, prospective cohort study the occurrence of MI had no relationship to homocysteine baseline plasma level. Furthermore, there was no strong association between homocysteine and the concentrations of any of these inflammation-sensitive proteins.
- [Show abstract] [Hide abstract]
ABSTRACT: Serum homocysteine levels, which increase with age, are now recognized as a vascular risk factor and are related to the development of heart failure and dementia in the elderly. However, relatively low serum homocysteine levels have also been reported to be an adverse prognostic factor in dialysis patients. The objective of the study was to analyze the prevalence, clinical significance, and prognostic value of serum homocysteine levels in patients older than 65 years, admitted to a general internal medicine hospitalization unit. We studied 337 hospitalized patients, 184 males and 153 females, aged 77.2+/-0.4 years, whose admission was not determined by an acute vascular event. We recorded past vascular events and vascular risk factors. We determined the body mass index (weight in kilograms divided by the square of height in meters), and cholesterol, triglyceride, folate, vitamin B12, and homocysteine levels. We also studied 36 control subjects (18 males and 18 females) of similar age. After discharge, we assessed the survival status of 301 patients by telephone recall. Survival curves were plotted by the method of Kaplan and Meier. Median survival was 1186 days. The 15th (9.6 micromol/L) and 50th (14.4 micromol/L) percentiles, as the lowest and highest cut-off points, were empirically defined as those related to a shorter survival. Serum homocysteine concentration was significantly positively correlated with age and serum creatinine and albumin concentrations, and negatively correlated with serum cobalamin and folate concentrations. The average serum homocysteine concentration for the patients group, as a whole, was 16.5+/-0.5 micromol/L, not significantly different from the control group, but with a much greater dispersion, as patients with congestive heart failure or cognitive impairment had higher serum homocysteine concentrations, and patients with sepsis, leukocytosis, and hypoalbuminemia had lower concentrations. Malnutrition was associated both with abnormally high and low homocysteine concentrations, and abnormally low and abnormally high homocysteine concentrations were both associated with higher mortality. In conclusion, low homocysteine levels in elderly non-vitamin-supplemented hospitalized patients should not be interpreted as a protective factor in some individuals. Instead, it may be considered as an effect of an inflammatory-malnutrition process associated with a poor prognosis.Metabolism 06/2006; 55(5):620-7. · 3.10 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Traditional risk factors do not explain all of the risk for incident coronary heart disease (CHD) events. Various new or emerging risk factors have the potential to improve global risk assessment for CHD. To summarize the results of 9 systematic reviews of novel risk factors to help the U.S. Preventive Services Task Force (USPSTF) evaluate the factors' clinical usefulness. Results from a MEDLINE search for English-language articles published from 1966 to September 2008, using the Medical Subject Heading terms cohort studies and cardiovascular diseases in combination with terms for each risk factor. Studies were included if the participants had no baseline cardiovascular disease and the investigators adjusted for at least 6 Framingham risk factors. Study quality was evaluated by using USPSTF criteria and overall quality of evidence for each risk factor by using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation framework. Each factor's potential clinical value was evaluated by using a set of criteria that emphasized the importance of the effect of that factor on the reclassification of intermediate-risk persons. 9 systematic reviews were conducted. C-reactive protein (CRP) was the best candidate for use in screening and the most rigorously studied, but evidence that changes in CRP level lead to primary prevention of CHD events is inconclusive. The other evaluated risk factors were coronary artery calcium score as measured by electron-beam computed tomography, lipoprotein(a) level, homocysteine level, leukocyte count, fasting blood glucose, periodontal disease, ankle-brachial index, and carotid intima-media thickness. The availability and validity of the evidence varied considerably across the risk factors in terms of aggregate quality, consistency of findings, and applicability to intermediate-risk persons in the general population. For most risk factors, no studies assessed their usefulness for reclassifying intermediate-risk persons. Because of lack of access to original data, no firm conclusions could be drawn about differences in risk prediction among racial and ethnic groups. The review did not emphasize within-cohort comparisons of multiple risk factors. The current evidence does not support the routine use of any of the 9 risk factors for further risk stratification of intermediate-risk persons.Annals of internal medicine 10/2009; 151(7):496-507. · 13.98 Impact Factor