Homocysteine has become a target for many basic and clinical investigators because of a clinical syndrome described almost 40 years ago. Homocysteine testing may be ordered as part of assessing a persons risk of cardiovascular disease, depending on the individuals age and other risk factors. Downloaded from access provided by university of western ontario on 021417. Role of homocysteine in the development of cardiovascular.
Relationship of homocysteine with cardiovascular disease. Design cross sectional study of the general population. What is already known on this topic there is an association between serum homocysteine concentration and cardiovascular disease, but it is not known whether the association is causal. Abstractalthough evidence suggests that the homocysteine hypothesis is still relevant as a predictor of cardiovascular risk, we cannot conclude that measuring the homocysteine level is useful in guiding treatment. Clinical practice guidelines cardiovascular disease in ckd. Cvd is among the diseases with multiple contributing factors, hence. Sulfur containing nonessential amino acid that is not found in the diet. Such patients have moderately elevated plasma homocysteine and greatly increased cardiovascular risk that is largely unex plained. The role of homocysteine as a causal risk factor for cardiovascular disease remains controversial. Studies are now in progress to estab lish whether such therapy will reduce cardiovascular risk. Elevated plasma homocysteine hcy concentration is considered a risk factor for cardiovascular disease and may also be associated with hypertension. The emergence of new risk factors for heart disease and other major human illnesses are often greeted with skepticism in the scientific community. Homocysteine as a risk factor for cardiovascular disease in patients treated by dialysis. Moderately elevated total plasma homocysteine levels have been reported in patients with overt hypothyroidism, a condition that is associated with an increased risk for cardiovascular disease.
Objective to examine the hypothesis that the higher rates of coronary heart disease chd in indians south asians compared with malays and chinese is partly attributable to differences in blood concentrations of homocysteine, and related blood concentrations of folate and vitamin b12. Homocysteine and cardiovascular disease slideshare. Our main findings were subsequently tested in tens of thousands of vascular disease cases and controls in many diverse settings and populations 1,4. A common single gene mutation that reduces the activity of an enzyme involved in folate metabolism mthfr is associated with a moderate. This association may be causalit is biologically plausible, fairly strong, graded, and an increase in plasma homocysteine preceeds the onset of vascular disease. When the levels get too high, it increases your risk of heart disease, heart attack, and stroke. Homocysteine an emerging cardiovascular risk factor. The basis for these conclusions is data from about 80 clinical and epidemiological studies. Folate, vitamin b 6, and vitamin b 12 contribute to the conversion of homocysteine to methionine by providing methyl groups, thereby decreasing homocysteine levels, as illustrated in the figure below.
An elevated level of total homocysteine thcy in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. In the hope2 trial of highrisk patients, treatment with folic acid, vi. Homocysteine and cardiovascular disease circulation research. Furthermore, studies of primary and secondary prevention show no evidence that taking folic acid or other b vitamins lowers the risk of cardiovascular events.
Vitamins, homocysteine and cardiovascular risk springerlink. Homocysteine has been evaluated as a potential marker of cardiovascular disease cvd in the general population and as a potential risk marker among people with cvd. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects. Homocysteine and vitamins in cardiovascular disease. In light of the numerous observational studies that have found a positive association between plasma homocysteine levels and the risk of cardiovascular disease, the results of two. Mthfr gene polymorphism, homocysteine and cardiovascular. As a free amino acid, it exists in either the reduced homocysteine, a thiol or oxidized homocystine, a disulfide rssr form.
Cardiovascular disease is believed to account for one third of all deaths worldwide, and the prevalence is still on the rise. A metaanalysis judith heinz, msc, 1siegfried kropf, phd,2 claus luley, md, and jutta dierkes, phd background. There were significant associations between homocysteine and the three diseases. That is because the body normally converts homocysteine into other products quickly. A common single gene mutation that reduces the activity of an enzyme involved in folate metabolism mthfr is associated with a moderate 20% increase in serum homocysteine. The realization that homocysteine is a risk factor for vascular disease coincided with observations initially made by lindenbaum et al 8 that homocysteine along with methylmalonic acid was a sensitive indicator of subtle vitamin b 12 deficiency in patients presenting with dementia, psychosis, ataxia, or neuropathy. The correlation of homocysteine with prevalent cardiovascular disease has. Homocysteine and reclassification of cardiovascular. A raised plasma level of the amino acid homocysteine is associated with increased risk of cardiovascular disease.
As a free amino acid, it exists in either the reduced homocysteine, a thiol or oxidized. Homocysteine hcy is an amino acid formed by demethylation of methionine. Measurement of total plasma homocysteine is the sum of. Homocysteine, folate, vitamin b12, and cardiovascular risk. While the present analysis will provide an insight into causeandeffect of hyperhomocysteinemia and cardiovascular diseases, the potential. Impaired renal function, enzymatic polymorphisms, and low levels of bgroup vitamins dispose to hyperhomocysteinaemia hhcy. In fact, a high level of homocysteine is a risk factor for heart disease. Relationship of homocysteine with cardiovascular disease and. Homocysteine, b vitamins, and cardiovascular disease nejm. An elevated plasma level of homocysteine has long been known as an independent predictor of cardiovascular disease. Homocysteine and risk of ischemic heart disease and stroke.
Homocysteine in health and disease annals of internal. Subsequent ecological, crosssectional, casecontrol, nested casecontrol, and cohort studies by and large indicate an association between elevated plasma homocysteine level and cardiovascular disease 58. There is an association between serum homocysteine concentration and cardiovascular disease, but it is not known whether the association is causal. Although links have been established between hyperhomocysteinemia and elevated risk for cardiovascular events, the precise role of plasma hcy in cardiovascular disease is unclear. Homocysteine was one of the nontraditional risk factors considered in the recommendation. Their data suggest that an increase in homocysteine levels is not likely to result in an increase in risk of coronary heart disease. When death due to cardiovascular disease which occurred in 50 patients was used as the end point in the analysis, the relation between homocysteine levels and mortality was slightly strengthened. Homocysteine and folate metabolism homocysteine is an amino acid not used in protein synthesis. Homocysteine testing in the screening, diagnosis, and management of cardiovascular disease and venous thromboembolic disease a. However, it is not known whether this also applies to patients with endstage renal disease. Robert clarke and colleagues conduct a metaanalysis of unpublished datasets to examine the causal relationship between elevation of homocysteine levels in the blood and the risk of coronary heart disease. Homocysteine, folate, and cardiovascular disease request pdf. Homocysteine an emerging cardiovascular risk factor article by pamlab.
Mthfr gene polymorphism, homocysteine and cardiovascular disease claudio cortese1 and corradino motti2 1department of internal medicine, university of tor vergata, via di tor vergata 5, 003 rome, italy. Although about half of americans have levels of cholesterol that place them at high risk of coronary artery disease, hypercholesterolemia is now considered only one risk factor within a complex amalgam of factors. Data sources medline was searched for articles published. Copper and homocysteine in cardiovascular diseases. Copperhomocysteine complexes and possible role in cardiovascular disease. Homocysteine, b vitamins, and risk of cardiovascular disease. Elevated circulating homocysteine levels have been found in people with cardiovascular disease. Homocysteine, vitamins, and cardiovascular disease aha journals. An extend metaanalysis suggested that an increment of homocysteine of 5 mmoll is comparable to the increase in the risk of coronary artery disease caused by cholesterol elevation of 0. Homocysteine, vitamins, and cardiovascular disease.
The methioninehomocysteine cycle and its effects on. It is a thiol compound derived from methionine and involved in two main metabolic pathways. Its associated with low levels of vitamins b6, b12, and folate, as well as renal disease. Homocysteine is an amino acid that has been evaluated as a potential marker of cardiovascular disease cvd and increased risk of thrombosis in the general population and as a potential risk marker for people with cvd and thrombotic disorders. Our report was careful to state that it remained to be seen whether lowering homocysteine would reduce the risk of cardiovascular disease. Obesity is a risk factor in developing renal disease 3 and weight loss programmes can help obese predialysis patients in by reducing proteinuria, bp and rate of renal decline 4. Cardiovascular diseases cvd as the name suggests, comprise of diseases of the heart and blood vessels. Homocysteine is an amino acid produced by the body and also is in your blood. Homocysteine is an amino acid that is typically present in very small amounts in all cells of the body.
Homocysteine the hidden factor and cardiovascular disease. Homocysteine testing in the screening, diagnosis, and management of cardiovascular disease and venous thromboembolic disease subsequently, prospective epidemiologic studies were conducted to determine if an elevated plasma level of homocysteine was an independent risk factor for cvd and could be used to improve current risk prediction models. However, danesh and lewingtons metaanalysis 8 indicates that the more rigorous the epidemiologic methods, the weaker the association. Homocysteine testing in the screening, diagnosis, and management of cardiovascular disease and venous thromboembolic disease. Homocysteine as a risk factor for cardiovascular disease. Objective to assess the relationship of homocysteine concentrations with vascular disease risk. Homocysteine and cardiovascular disease aharon roberts fcsfn 648 2. The association between homocysteinelowering interventions and risk of. Elevated plasma homocysteine levels have re cently been implicated as a new risk factor for coronary artery disease. The homocysteine cardiovascular disease association was slightly strengthened in women, but when the highest and the lowest quintiles of homocysteine were compared, risk of hypertension showed a threefold increase and a twofold increase in women and men respectively. Homocysteine lowering with folic acid and b vitamins in. Cardiovascular disease homocysteine is a sulfurcontaining amino acid, coohchch 2ch 2shnh 3, that is formed during methionine metabolism.
It may also be ordered following a heart attack or stroke to help guide treatment. Its redox chemistry is dominated by its thiol group sh, which in. Medical coverage policy homocysteine testing in the. The hyperhomocysteine basis of cardiovascular disease homocysteine is a sulfurcontaining amino acid, coohchch 2ch 2shnh 3, that is formed during methionine metabolism. Cardiovascular disease cvd1 is the leading cause of mortality in the united states and in most western countries. In the general population, increased homocysteine concentrations are a risk factor for cardiovascular disease and mortality. The clinical significance of elevated plasma homocysteine. Homocysteine and neurologic disease neurology jama. Elevated plasma homocysteine hcy concentration is considered a. Objectives the purpose of this study was to examine whether adding homocysteine hcy to a model based on traditional cardiovascular disease cvd risk factors improves risk classification. Elevated homocysteine hcy levels can be caused by a number of factors, including folate and bvitamin deficiency, preexisting atherosclerotic disease, diabetes and various drugs. Homocysteine, a marker of cardiovascular disease risk, is. Since vitamins b6, b12, and folate are necessary to metabolize homocysteine, increased levels of the amino acid may be a sign of deficiency in those vitamins.
Information has been emerging regarding a connection between homocysteine metabolism and cognitive function, from mild. In epidemiologic studies, the plasma total homocysteine level has been found to be a risk factor for cardiovascular disease. Homocysteine testing in the screening, diagnosis, and. Pdf elevated homocysteine hcy levels can be caused by a number of factors, including folate and bvitamin deficiency, preexisting. Context it has been suggested that total blood homocysteine concentrations are associated with the risk of ischemic heart disease ihd and stroke. Role of homocysteine in the development of cardiovascular disease. Hyperhomocysteinemia clinmed international library. The observation that blood cu and hcy were simultaneously elevated in patients with cardiovascular disease mansoor et al. Wilcken the possibility that modest elevations in the level of blood homocysteine hyperhomocysteinaemia could contribute to cardiovascular disease arose from investigation of patients with rare, severe homocysteine elevations caused by. Background data on using hcy to reclassify individuals in various risk categories beyond traditional approaches have not been adequately scrutinized.
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