This Article Free upon publication Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Malinow, M. R. Articles by Krauss, R. M. Search for Related Content PubMed PubMed Citation Articles by Malinow, M. R. Articles by Krauss, R. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Diets Vitamins Related Collections AHA Statements and Guidelines

(Circulation. 1999;99:178-182.)
© 1999 American Heart Association, Inc.

AHA Science Advisory

Homocyst(e)ine, Diet, and Cardiovascular Diseases

A Statement for Healthcare Professionals From the Nutrition Committee, American Heart Association

M. René Malinow, MD; Andrew G. Bostom, MD; Ronald M. Krauss, MD

Correspondence to M. René Malinow, MD, Oregon Regional Primate Research Center, 505 NW 185th Ave, Beaverton, OR 97006-3448. E-mail malinowr{at}ohsu.edu

Key Words: homocysteine • diet • cardiovascular diseases • vitamins • folic acid • AHA Science Advisory

Homocysteine and Diet

Homocysteine is a sulfur-containing amino acid, rapidly oxidized in plasma to the disulfides homocystine and cysteine-homocysteine (Figure 1). Plasma/serum total homocysteine, also termed homocyst(e)ine, is the sum of homocysteine in all 3 components. Figure 2 displays factors involved in the metabolism of homocysteine, including its metabolic relationship to methionine. Although dietary intake of total protein and methionine does not correlate significantly with blood homocyst(e)ine,¹ a single dose of oral methionine (100 mg/kg body weight) can elevate homocyst(e)ine levels, and as described further below, this has been used as a diagnostic test to detect disordered homocyst(e)ine metabolism. Because variable changes in homocyst(e)ine levels have been observed postprandially,² it is customary to obtain measurements in the fasting state. Normal levels of fasting plasma homocyst(e)ine are considered to be between 5 and 15 µmol/L. Moderate, intermediate, and severe hyperhomocyst(e)inemia refer to concentrations between 16 and 30, between 31 and 100, and >100 µmol/L, respectively.³

View larger version (15K): [in this window] [in a new window]   Figure 1. Molecular species of homocysteine.

View larger version (28K): [in this window] [in a new window]   Figure 2. Simplified outline of methionine/homocysteine metabolism. Vitamin coenzymes and substrates: THF, tetrahydrofolate; B2, riboflavin; B6, vitamin B6 as its biological active form, ie, pyridoxal 5'-phosphate; and B12, methyl cobalamin. Intermediate metabolite: DMG, dimethylglycine.

Several vitamins function as cofactors and substrates in the metabolism of methionine and homocysteine (Figure 2). Folic acid and cyanocobalamin (vitamin B₁₂) regulate metabolic pathways catalyzed by the enzymes methylenetetrahydrofolate reductase (MTHFR) and methionine synthase, respectively, whereas pyridoxine (vitamin B₆) is a cofactor for cystathionine ß-synthase. A number of studies have shown inverse relationships of blood homocyst(e)ine concentrations with plasma/serum levels of folic acid, vitamin B₆, and vitamin B₁₂.^{4 5 6}

Administration of supplemental folic acid in doses between 0.2 and 15 mg/d can lower plasma homocyst(e)ine levels without apparent toxicity.^{7 8 9} On the basis of meta-analysis of 12 clinical studies, all but 1 of which was a placebo-controlled trial, it has been estimated that a 25% reduction in homocyst(e)ine concentration can be achieved with mean supplementation of 0.5 to 5.7 mg of folic acid per day; an additional 7% lowering has been observed after the addition of vitamin B₁₂ (0.02 to 1 mg/d; mean, 0.5 mg).¹⁰ A recent report of the Food and Nutrition Board of the Institute of Medicine has recommended an upper limit of 1 mg/d folic acid on the basis of the possibility that higher doses may mask signs of vitamin B₁₂ deficiency in some subjects.¹¹ In overt cobalamin deficiency with intermediate and severe hyperhomocyst(e)inemia, vitamin B₁₂ can normalize homocyst(e)ine concentration in 70% of cases.¹² In an open-label, uncontrolled study, vitamin B₆ at 250 mg/d was without effect in reducing basal homocyst(e)ine levels, but doses of 50 to 250 mg/d reduced homocyst(e)ine levels after a methionine-loading test by 25%.¹³ Subsequently, a study that used a randomized, placebo-controlled, 2x2 factorial design demonstrated that 50 mg of vitamin B₆ per day independently reduced the post–methionine-loading increase in homocyst(e)ine levels by 22%.¹⁴ In a placebo-controlled study,¹⁵ a combination of multiple agents including folic acid (0.65 mg/d), vitamin B₆ (10 mg/d), and vitamin B₁₂ (0.4 mg/d) was very effective in reducing homocyst(e)ine levels in patients with moderate or intermediate hyperhomocyst(e)inemia. It has been reported, however, that increased vitamin intake from food sources (1 mg of folic acid, 12.2 mg of pyridoxine, and 50 µg of cyanocobalamin per day) failed to maintain normal homocyst(e)ine levels attained previously by vitamin supplementation.¹⁶

Other vitamins may also influence plasma homocyst(e)ine levels. Daily food intake of 0.6 mg of riboflavin, a vitamin that can function as a cofactor for MTHFR,¹⁷ results in modest reductions in homocyst(e)ine (0.475 µmol/L),¹ and pharmacological doses of nicotinic acid (3000 mg/d) may cause significant elevations.¹⁸ Users of multivitamin supplements in observational studies have lower homocyst(e)ine levels than nonusers, as well as higher concentrations of plasma folic acid and vitamins B₆ and B₁₂.¹⁹ The daily intake of fortified cereals containing 499 and 650 µg of folic acid per serving and the recommended dietary amount (RDA) of other vitamins reduced homocyst(e)ine by 11% and 14%, respectively.²⁰

A relatively common prevalence of the heat-labile variant of MTHFR has been shown to result from a cytosine to thymine (C to T) mutation at nucleotide 677.^{21 22} Although an increased prevalence of thermolabile MTHFR and T/T homozygotes has been reported among patients with coronary artery disease (CAD),^{19 21 22 23 24} this has not been confirmed in several other studies.^{25 26 27 28} T/T homozygotes have been reported to have higher geometric mean fasting homocyst(e)ine levels than C/T heterozygotes or C/C homozygotes when folate status was below the population median, but no differences in fasting homocyst(e)ine levels were detected between persons with different genotypes when plasma folate was at or above the population median.²⁹ The MTHFR genotype has been reported to influence the homocyst(e)ine response to folic acid. Reduction was greater in subjects with T/T than with C/C or C/T genotypes.¹⁹ Moreover, in 21 of 37 subjects with homocyst(e)ine 40 µmol/L, in whom the frequency of the T/T genotype was 92%, homocyst(e)ine levels were normalized with supplemental intake of folic acid as low as 200 µg/d.⁸ It is likely but not proven that a folate-rich diet ingested by subjects with the T/T genotype may be more effective in lowering homocyst(e)ine levels than a similar diet ingested by subjects with C/C or C/T genotypes.

Homocyst(e)ine and Coronary, Cerebral, and Peripheral Arterial Diseases

Homocystinuria is a rare autosomal recessive genetic disorder (1:200 000 births) that usually results from defective activity of cystathionine ß-synthase. Patients have severe hyperhomocyst(e)inemia and a variety of abnormalities, including a high incidence of vascular pathology that may result in early death from myocardial infarction, stroke, or pulmonary embolism.³⁰ Biochemical and pathological studies in homocystinuric children led McCully and Wilson³¹ to propose that elevated blood homocysteine may cause arteriosclerosis. Observations in 80 clinical and epidemiological studies have suggested that elevated homocyst(e)ine is a risk factor for atherosclerotic vascular disease and for arterial and venous thromboembolism.³² Moreover, moderate and intermediate hyperhomocyst(e)inemia is present in 12% to 47% of patients with coronary, cerebral, or peripheral arterial occlusive diseases³ ; these patients do not exhibit the systemic abnormalities characteristic of homocystinuria (see reviews in Reference 3³ and References 33³³ to 38).

In a meta-analysis,³⁶ the odds ratio (OR) for CAD in subjects with hyperhomocyst(e)inemia was 1.7 in 15 studies (95% confidence interval [CI], 1.5 to 1.9). For stroke, the OR was 2.5 in 9 studies (95% CI, 2.0 to 3.0), and for peripheral vascular disease, the OR was 6.8 in 5 studies (95% CI, 2.9 to 15.8). Since this meta-analysis,³⁶ 22 reports involving 7800 subjects, including 9 cross-sectional^{39 40 41 42 43 44 45 46 47} and 13 case-controlled^{48 49 50 51 52 53 54 55 56 57 58 59 60} studies analyzed by Refsum et al,³² have provided further evidence for a relationship between homocyst(e)ine and coronary, cerebral, and peripheral atherosclerosis. In this period, only 2 cross-sectional^{61 62} and 2 case-control studies^{57 63} on 850 subjects failed to show an association between homocyst(e)ine and atherosclerosis; these studies included patients in the acute phase of myocardial infarction or stroke, in which homocyst(e)ine levels are decreased.^{64 65} The strongest evidence for a relationship between homocyst(e)ine and cardiovascular disease risk was provided by 6 prospective studies^{39 66 67 68 69 70} with follow-ups from 1.4 to 12.8 years on 830 cases and 1872 controls. However, 5 prospective studies^{28 71 72 73 74} on 995 cases and 1850 controls with follow-ups from 3.3 to 11 years failed to demonstrate such an association. For this reason, and in the absence of a controlled clinical intervention trial, it is premature to conclude that homocyst(e)ine levels are predictive of the development of cardiovascular disease.

Risk of CAD showed a dose-response effect across the entire distribution of basal^{36 39 57 59} and post–methionine-load⁵⁹ levels of homocyst(e)ine, and this effect was statistically independent of most conventional factors for atherosclerosis,^{32 39 59 75} although a multiplicative interaction with smoking and blood pressure has been reported.⁵⁹ Moreover, a recent study⁶⁸ demonstrated that the risk of death in 587 men and women with CAD was highly correlated with basal levels of homocyst(e)ine; after a median follow-up of 4.6 years, the mortality estimate for subjects with homocyst(e)ine 15.0 µmol/L was 24.7% compared with 3.8% in subjects with homocyst(e)ine <9.0 µmol/L. Finally, the more markedly elevated fasting homocyst(e)ine levels found in persons with dialysis-dependent, end-stage renal disease may also contribute independently to the excess incidence of fatal and nonfatal vascular disease outcomes in this patient population.⁶⁷

On the basis of these positive associations (excluding Reference 67⁶⁷ ), Omenn et al⁷⁶ provided a "best estimate" for the increased risk of CAD mortality associated with elevated plasma levels of homocyst(e)ine. The authors compared relative risks between homocyst(e)ine levels of >15 and <10 µmol/L after adjustment for other cardiovascular risk factors and suggested that such risk difference is similar to that between total serum cholesterol levels of 7.1 and 4.9 mmol/L (275 and 189 mg/dL).

Vitamin Intake, Homocyst(e)ine, and Cardiovascular Disease

In the case-control study of arterial diseases described above,^{5 59} folate deficiency was more common in cases, and plasma vitamin B₆ below the lowest 20th percentile (<23.3 nmol/L) for control subjects was associated with increased risk for vascular disease, ie, OR=1.84 (95% CI, 1.39 to 2.42). Of note, the relationship between vitamin B₆ and vascular disease was shown to be independent of homocyst(e)ine levels.⁵ Morrison et al⁷⁷ demonstrated in the prospective Nutrition Canada Survey that the risk of fatal CAD was associated with low serum folate in 165 CAD deaths in subjects among 5056 men and women monitored for 20 years.

In a subset of subjects from the Atherosclerosis Risk In Communities study,⁷⁸ carotid artery medial-intimal thickening was associated with high levels of homocyst(e)ine. Moreover, in a subset of subjects from the Framingham Heart Study,⁷⁹ the stenosis was inversely proportional to reported intakes of both folic acid and vitamin B₆. Another analysis from the Framingham Study⁸⁰ indicated that intake of fruits and vegetables was inversely related to incidence of stroke over a 20-year follow-up. Although homocyst(e)ine levels were not measured, the authors discussed, among other factors, the potential role of dietary folic acid in lowering homocyst(e)ine as a plausible mechanism involved in the protective effects of diet.

Users of multivitamins have been reported to have a reduced prevalence of CAD compared with nonusers.⁵⁹ These findings have been extended in prospective observations conducted by Rimm et al⁸¹ in 80 082 women from the Nurses' Health Study. During a 14-year follow-up, the risk for fatal and nonfatal CAD was considerably lower among women who used multivitamins 4 to 7 times per week than among nonusers (risk ratio=0.76; 95% CI, 0.65 to 0.90) after multivariate adjustments. Caution must be exercised in interpreting observational studies, however, because of the possible effects of differences in unmeasured behaviors or risk factors that may be associated with diet and vitamin intake. Moreover, the relationship of vitamin use to homocyst(e)ine levels was not evaluated in the study by Rimm et al.⁸¹

Dietary Guidance With Regard to Homocyst(e)ine and Cardiovascular Disease

Population Guidelines
On the basis of the apparent relationship of plasma homocyst(e)ine to cardiovascular disease risk and the estimated influence of folic acid on homocyst(e)ine levels, Boushey et al³⁶ suggested that a 350 µg/d increase in folic acid intake in men and a 280 µg/d increase in women could potentially prevent 30 500 and 19 000 vascular deaths annually in men and women, respectively. However, in the absence of prospective, placebo-controlled intervention trials of the effects of diet- or vitamin-mediated homocyst(e)ine reductions on incidence of cardiovascular disease, the clinical benefits of such interventions are unknown.

A recent report of the Food and Nutrition Board of the Academy of Sciences Institute of Medicine includes RDAs for folic acid, vitamin B₆, and vitamin B₁₂ of 400 µg, 1.7 mg, and 2.4 µg, respectively, for nonpregnant, nonlactating individuals.¹¹ Because a significant proportion of the population does not meet the current RDAs for folate intake,¹¹ a reasonable population approach is to recommend an increase in the intake of foods containing those vitamins, ie, ready-to-eat fortified cereals, leafy green vegetables, fruits, and legumes as sources of folate; ready-to-eat fortified cereals, noncitrus fruits, poultry, beef, and certain vegetables (eg, artichoke, asparagus, beans, and cabbage) as sources of vitamin B₆; and beef, poultry, fish, and ready-to-eat fortified cereals as sources of vitamin B₁₂ (see Reference 11¹¹ for more extensive information). These dietary modifications could result in elevated vitamin status and perhaps decreased homocyst(e)ine levels. However, because 10% to 30% of older people may malabsorb food-bound B₁₂, it is advisable for those older than 50 years to meet their RDA mainly by consuming food fortified with B₁₂ or a B₁₂-containing supplement.¹¹ Moreover, on the basis of relative differences in bioavailability, the RDA guidelines equate 100 µg of folic acid from unfortified foods to 60 µg from fortified food and 50 µg from supplements.¹¹ Because of methodological problems, food folate content in current databases may be significantly underestimated.⁸² Finally, prolonged heating or boiling, followed by discarding of water, or microwave heating may reduce folate content of food.⁸³

A complementary approach has been instituted as of January 1, 1998: the US Food and Drug Administration (FDA) has issued regulations requiring all "enriched" cereal grains to be fortified with folic acid at a concentration of 1.4 mg/kg grains to prevent neural tube birth defects. It has been estimated that this level of fortification would increase folic acid intake by 80 to 100 µg per day in women of childbearing potential and by 70 to 120 µg per day in adults older than 50 years.⁸⁴ Whether this level of fortification will lower homocyst(e)ine concentrations in CAD patients needs to be determined. However, as described above, cereal products have been shown recently to lower homocyst(e)ine in CAD patients when they were fortified with 4 to 5 times the levels of fortification mandated by the US FDA.²⁰

Detection and Management of Elevated Fasting Homocyst(e)ine

Levels of homocyst(e)ine have been remarkably similar between laboratories in studies conducted by different investigators using several methods,² perhaps because in the United States, determinations are routinely validated between laboratories as required by government regulations. With a method by which homocyst(e)ine was measured by high-performance chromatography with electrochemical detection, the within-assay precision showed a coefficient of variation of 1.1%, and the between-assay coefficient of variation was 2.1 to 11.4%,⁸⁵ whereas the coefficient of variation was 3.2% for within-pair quality-control specimens.⁶⁹ The cost of homocyst(e)ine analyses, coupled with the lack of definitive evidence for the clinical benefits of reducing homocyst(e)ine levels, precludes recommendations for population-wide screening at the present time. Thus, some researchers consider that a reasonable approach is to determine levels of fasting homocyst(e)ine in "high-risk patients," ie, in those with strong family history for premature atherosclerosis or with arterial occlusive diseases, particularly in the absence of other risk factors, as well as in members of their families, because hyperhomocyst(e)inemia in CAD seems to be transmitted, at least in part, through an autosomal dominant mechanism.⁸⁶ Other conditions that may be associated with high homocyst(e)ine are advanced age,³³ hypothyroidism,⁸⁷ impaired kidney function,⁸⁸ systemic lupus erythematosus,⁸⁹ and certain medications, eg, nicotinic acid,¹⁸ nitrous oxide exposure,⁹⁰ theophylline,⁹¹ methotrexate,⁹² and L-dopa.⁹³

After confirmation of high homocyst(e)ine concentration, it is important to check the vitamin status owing to the inverse relationships reported between homocyst(e)ine and blood levels of folate, B₆, and B₁₂.^{4 5 6} A useful algorithm for the diagnosis of vitamin B₁₂ deficiency, beyond the determination of blood levels of this vitamin, is described in Reference 11¹¹ .

There is currently no firm basis for recommending specific therapeutic targets for homocyst(e)ine levels. Moreover, as reviewed above, the risk associated with homocyst(e)ine is continuous across the concentration distribution.^{36 39 57 59} Evidence that vitamin supplementation favorably affects the evolution of atherosclerosis is limited to a single observation in 38 patients with homocyst(e)ine >14 µmol/L, in whom high doses of folic acid (2.5 and 5 mg/d) together with pyridoxine and vitamin B₁₂ resulted in reduced rate of progression of carotid plaque determined by ultrasonography after a mean follow-up of 4.4±1.5 years.⁹⁴ In the study of men and women younger than 60 years quoted above,⁵⁹ risk began to rise from the middle of the distribution (10.3 µmol/L). In a study contrasting survivors of myocardial infarction and noncoronary subjects,⁵⁷ the referent level (OR=1.0) was 9.8 µmol/L. Moreover, the referent value for risk of death associated with homocyst(e)ine was <9.0 µmol/L⁶⁸ or <10.0 µmol/L.⁷⁶ Thus, a basal homocyst(e)ine level <10 µmol/L is a reasonable therapeutic goal for subjects at increased risk, rather than the definition of "normal" based on population statistical values of the mean±2 SDs.

Accordingly, subjects with basal homocyst(e)ine 10.0 µmol/L should be advised to consume the diet indicated above. Chait et al⁹⁵ demonstrated that a folic acid–fortified diet reduced homocyst(e)ine in certain patients at high risk for cardiovascular disease, but other studies^{16 96} failed to show effectiveness of nonfortified, self-selected prescribed diets. Consequently, patients should repeat the homocyst(e)ine analysis after 1 month on the prescribed diet. If reduction in plasma homocyst(e)ine is not achieved, daily supplementation with a multivitamin containing inter alia 400 µg of folic acid, 2 mg of vitamin B₆, and 6 µg of vitamin B₁₂ or intake of "100% fortified" breakfast cereal also containing those amounts of vitamins per serving may be suggested, with repeat analysis at the end of 1 month. If such treatment is ineffective in lowering basal homocyst(e)ine in high-risk patients, a combination of folic acid (1 mg), vitamin B₆ (25 mg), and vitamin B₁₂ (0.5 mg) can be prescribed daily, after vitamin B₁₂ deficiency has been ruled out or adequately treated. If repeat analysis after 1 month shows ineffective homocyst(e)ine lowering, a trial of betaine (3 g BID) may be considered, although this remains investigational. Betaine, an intermediate metabolite from choline, is a methyl group donor for the enzymatic remethylation of homocysteine to methionine³⁰ (see Figure 2). Betaine has been found to be effective in reducing basal hyperhomocyst(e)inemia in subjects resistant to B vitamin therapy.⁹⁷

Methionine-Load Test

Homocyst(e)ine levels after a methionine-load test may be measured in high-risk patients with normal basal levels of homocyst(e)ine to identify those individuals with postload hyperhomocyst(e)inemia. The test measures homocyst(e)ine before and after the intake of 100 mg of methionine (dissolved in orange juice) per kilogram of body weight. Although multiple sampling strategies have been described, the 2-hour test has been validated extensively,⁹⁸ and it seems more practical than later blood sampling. This test may uncover 39% of subjects with homocyst(e)ine-related cardiovascular disease risk but with normal basal homocyst(e)ine levels.⁹⁹ The Table shows the 80th percentile of delta and absolute homocyst(e)ine levels in 2-hour post–methionine-load tests observed in 363 subjects free of clinically apparent vascular disease. The data, stratified by age and sex, confirmed that women have higher deltas and absolute post–methionine-load homocyst(e)ine levels than men; these values increase with age in women but not in men. Values equal to or above those indicated in the Table could be associated with enhanced risk for vascular disease.⁵⁹

View this table: [in this window] [in a new window]   Table 1. Post–Methionine-Load Test in 363 Subjects Without Clinically Apparent Vascular Disease

As noted above, it has been reported that post–methionine-load delta homocyst(e)ine levels were reduced by an average of 22% with vitamin B₆ (50 mg/d)¹⁴ but not by folic acid supplementation up to 5 mg/d. Thus, it may not be possible to "normalize" the methionine-load response in all patients, and coupled with the lack of evidence for the benefit of a reduced response, the clinical value of this test remains uncertain. Moreover, when costs of the test and the need for adequate clinical facilities are considered, the methionine-load test may be reserved for research purposes.

Conclusions

Although there is considerable epidemiological evidence for a relationship between plasma homocyst(e)ine and cardiovascular disease, not all prospective studies have supported such a relationship. Moreover, despite the potential for reducing homocyst(e)ine levels with increased intake of folic acid, it is not known whether reduction of plasma homocyst(e)ine by diet and/or vitamin therapy will reduce cardiovascular disease risk.^{100 101} Until results of controlled clinical trials become available, population-wide screening is not recommended, and emphasis should be placed on meeting current RDAs for folate, as well as vitamins B₆ and B₁₂, by intake of vegetables, fruits, legumes, meats, fish, and fortified grains and cereals. A high-risk strategy may include screening for fasting plasma homocyst(e)ine associated with augmented risk status, ie, 10.0 µmol/L, in selected patients with personal or family history of premature cardiovascular disease, as well as in those with malnutrition, malabsorption syndromes, hypothyroidism, renal failure, or systemic lupus erythematosus; those taking certain medications, eg, nicotinic acid, theophylline, bile acid–binding resins, methotrexate, and L-dopa; or those with recent nitrous oxide exposure. In these patients, it may be advisable to increase their intake of vitamin-fortified foods and/or to suggest the daily use of supplemental vitamins, ie, 0.4 mg of folic acid, 2 mg of vitamin B₆, and 6 µg of vitamin B₁₂, with appropriate medical evaluation and monitoring. Treatment may include higher doses of those vitamins according to the response of homocyst(e)ine, as discussed in the text. However, such treatment is still considered experimental, pending results from intervention trials showing that homocyst(e)ine lowering favorably affects the evolution of arterial occlusive diseases.

Acknowledgments

This work was supported in part by grants from the National Institutes of Health (RR00163 to Dr Malinow, HL-56908-01A1 to Dr Bostom, and HL-18574 to Dr Krauss).

Footnotes

References for this article may be found in the on-line version that appears on the American Heart Association Web site (http://www.americanheart.org/Scientific/statements/1999/019901.html) and on the Circulation Web site listed below.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee in September 1998. A single reprint is available by calling 800-242-8721 (US only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX 75231-4596. Ask for reprint No. 71-0157.

References

1. Shimakawa T, Nieto FJ, Malinow MR, Chambless LE, Schreiner PJ, Szklo M. Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults. Ann Epidemiol. 1997;7:285–293.[Medline] [Order article via Infotrieve]

2. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem. 1993;39:1764–1779.[Abstract]

3. Kang SS, Wong PWK, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Ann Rev Nutr. 1992;12:279–298.[Medline] [Order article via Infotrieve]

4. Kang SS, Wong PWK, Norusis M. Homocysteinemia due to folate deficiency. Metabolism. 1987;36:458–462.[Medline] [Order article via Infotrieve]

5. Robinson K, Arheart K, Refsum H, Brattstrom L, Boers G, Ueland P, Rubba P, Palma-Reis R, Meleady R, Daly L, Witteman J, Graham I. Low circulating folate and vitamin B₆ concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease: European COMAC Group. Circulation. 1998;97:437–443.[Abstract/Free Full Text]

6. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993;270:2693–2698.[Abstract/Free Full Text]

7. Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr. 1996;126:1276S–1280S.

8. Guttormsen AB, Ueland PM, Nesthus I, Nygard O, Schneede J, Vollset SE, Refsum H. Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (40 µmol/liter): the Hordaland Homocysteine Study. J Clin Invest. 1996;98:2174–2183.[Medline] [Order article via Infotrieve]

9. Bostom AG, Shemin D, Lapane KL, Hume AL, Yoburn D, Nadeau MR, Bendich A, Selhub J, Rosenberg IH. High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients. Kidney Int. 1996;49:147–152.[Medline] [Order article via Infotrieve]

10. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ. 1998;316:894–898.[Abstract/Free Full Text]

11. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B₆, Folate, Vitamin B₁₂, Pantothenic Acid, Biotin, and Choline. Food and Nutrition Board. Washington, DC: Institute of Medicine (National Academy Press); 1998.

12. Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988;318:1720–1728.[Abstract]

13. Franken DG, Boers GH, Blom HJ, Trijbels FJ, Kloppenborg PW. Treatment of mild hyperhomocysteinemia in vascular disease patients. Arterioscler Thromb. 1994;14:465–470.[Abstract/Free Full Text]

14. Bostom AG, Gohh RY, Beaulieu AJ, Nadeau MR, Hume AL, Jacques PF, Selhub J, Rosenberg IH. Treatment of hyperhomocysteinemia in renal transplant recipients: a randomized, placebo-controlled trial. Ann Intern Med. 1997;127:1089–1092.[Abstract/Free Full Text]

15. Ubbink JB, Becker PJ, Vermaak WJ, Delport R. Results of B-vitamin supplementation study used in a prediction model to define a reference range for plasma homocysteine. Clin Chem. 1995;41:1033–1037.[Abstract/Free Full Text]

16. Ubbink JB, Van der Merwe A, Vermaak WJ, Delport R. Hyperhomocysteinemia and the response to vitamin supplementation. Clin Investig. 1993;71:993–998.

17. Daubner SC, Matthews RG. Purification and properties of methylenetetrahydrofolate reductase from pig liver. J Biol Chem. 1982;257:140–145.[Abstract/Free Full Text]

18. Garg R, Malinow MR, Pettinger M, Hunninghake D. Treatment with niacin increases plasma homocyst(e)ine levels. Circulation. 1996;94(suppl I):I-457. Abstract.

19. Malinow MR, Nieto FJ, Kruger WD, Duell PB, Hess DL, Gluckman RA, Block PC, Holzgang CR, Anderson PH, Seltzer D, Upson B, Lin QR. The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes. Arterioscler Thromb Vasc Biol. 1997;17:1157–1162.[Abstract/Free Full Text]

20. Malinow MR, Duell PB, Hess DL, Anderson PH, Kruger WD, Phillipson BE, Gluckman RA, Block PC, Upson BM. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med. 1998;338:1009–1015.[Abstract/Free Full Text]

21. Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, Rozen R. Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet. 1994;7:551. Published erratum.

22. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–113.[Medline] [Order article via Infotrieve]

23. Kang SS, Wong PW, Susmano A, Sora J, Norusis M, Ruggie N. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet. 1991;48:536–545.[Medline] [Order article via Infotrieve]

24. Ou T, Yamakawa-Kobayashi K, Arinami T, Amemiya H, Fujiwara H, Kawata K, Saito M, Kikuchi S, Noguchi Y, Sugishita Y, Hamaguchi H. Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case-control study. Atherosclerosis. 1998;137:23–28.[Medline] [Order article via Infotrieve]

25. Schwartz SM, Siscovick DS, Malinow MR, Rosendaal FR, Beverly RK, Hess DL, Psaty BM, Longstreth WT Jr, Koepsell TD, Raghunathan TE, Reitsma PH. Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene. Circulation. 1997;96:412–417.[Abstract/Free Full Text]

26. Wilcken DE, Wang XL, Sim AS, McCredie RM. Distribution in healthy and coronary populations of methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Arterioscler Thromb Vasc Biol. 1996;16:878–882.[Abstract/Free Full Text]

27. Ma J, Stampfer MJ, Hennekens CH, Frosst P, Selhub J, Horsford J, Malinow MR, Willett WC, Rozen R. Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation. 1996;94:2410–2416.[Abstract/Free Full Text]

28. Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis CE. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphism, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1998;98:204–210.[Abstract/Free Full Text]

29. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J, Rozen R. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996;93:7–9.[Abstract/Free Full Text]

30. Mudd SH, Levy HL, Skovby F. Disorders in transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Basis of Metabolic Disease. New York, NY: McGraw Hill; 1995:1279–1327.

31. McCully KS, Wilson RB. Homocysteine theory of arteriosclerosis. Atherosclerosis. 1975;22:215–227.[Medline] [Order article via Infotrieve]

32. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med. 1998;49:31–62.[Medline] [Order article via Infotrieve]

33. Malinow MR. Homocyst(e)ine and arterial occlusive diseases. J Intern Med. 1994;236:603–617.[Medline] [Order article via Infotrieve]

34. Malinow MR. Hyperhomocyst(e)inemia: a common and easily reversible risk factor for occlusive atherosclerosis. Circulation. 1990;81:2004–2006.[Free Full Text]

35. Ueland PM, Refsum H, Brattstrom L. Plasma homocysteine and cardiovascular disease. In: Francis RB Jr, ed. Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function. New York, NY: Marcel Dekker; 1992:183–236.

36. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA. 1995;274:1049–1057.[Abstract/Free Full Text]

37. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol. 1996;27:517–527.[Abstract]

38. Duell PB, Malinow MR. Homocyst(e)inemia, and risk of atherosclerosis: a clinical approach to evaluation and management. Endocrinologist. 1998;8:170–177.

39. Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH, Nordrehaung JE. Serum total homocysteine and coronary heart disease. Int J Epidemiol. 1995;24:704–709.[Abstract/Free Full Text]

40. van den Berg M, Stehouwer CD, Bierdrager E, Rauwerda JA. Plasma homocysteine and severity of atherosclerosis in young patients with lower-limb atherosclerotic disease. Arterioscler Thromb Vasc Biol. 1996;16:165–171.[Abstract/Free Full Text]

41. Glueck CJ, Shaw P, Lang JE, Tracy T, Sieve-Smith L, Wang Y. Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients. Am J Cardiol. 1995;75:132–136.[Medline] [Order article via Infotrieve]

42. Bachmann J, Tepel M, Raidt H, Riezler R, Graefe U, Langer K, Zidek W. Hyperhomocysteinemia and the risk for vascular disease in hemodialysis patients. J Am Soc Nephrol. 1995;6:121–125.[Abstract]

43. Currie IC, Wilson YG, Scott J, Day A, Stansbie D, Baird RN, Lamont PM, Tennant WG. Homocysteine: an independent risk factor for the failure of vascular intervention. Br J Surg. 1996;83:1238–1241.[Medline] [Order article via Infotrieve]

44. Tonstad S, Joakimsen O, Stensland-Bugge E, Leren TP, Ose L, Russell D, Bonaa KH. Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects. Arterioscler Thromb Vasc Biol. 1996;16:984–991.[Abstract/Free Full Text]

45. Robinson K, Gupta A, Dennis V, Arheart K, Chaudhary D, Green R, Vigo P, Mayer EL, Selhub J, Kutner M, Jacobsen DW. Hyperhomocysteinemia confers an independent increased risk of atherosclerosis in end-stage renal disease and is closely linked to plasma folate and pyridoxine concentrations. Circulation. 1996;94:2743–2748.[Abstract/Free Full Text]

46. Tonstad S, Refsum H, Sivertsen M, Christophersen B, Ose L, Ueland PM. Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives. Pediatr Res. 1996;40:47–52.[Medline] [Order article via Infotrieve]

47. Tonstad S, Refsum H, Ueland PM. Association between plasma total homocysteine and parental history of cardiovascular disease in children with familial hypercholesterolemia. Circulation. 1997;96:1803–1808.[Abstract/Free Full Text]

48. Bots ML, Launer LJ, Lindemans J, Hofman A, Grobbee DE. Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: the Rotterdam Study. J Intern Med. 1997;242:339–347.[Medline] [Order article via Infotrieve]

49. Dalery K, Lussier-Cacan S, Selhub J, Davignon J, Latour Y, Genest J Jr. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate. Am J Cardiol. 1995;75:1107–1111.[Medline] [Order article via Infotrieve]

50. Hopkins PN, Wu LL, Wu J, Hunt SC, James BC, Vincent GM, Williams RR. Higher plasma homocyst(e)ine and increased susceptibility to adverse effects of low folate in early familial coronary artery disease. Arterioscler Thromb Vasc Biol. 1995;15:1314–1320.[Abstract/Free Full Text]

51. Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A, Kottke-Marchant K, Savon SR, Selhub J, Nissen SE, Kutner M, Topol EJ, Jacobsen DW. Hyperhomocysteinemia and low pyridoxal phosphate: common and independent reversible risk factors for coronary artery disease. Circulation. 1995;92:2825–2830.[Abstract/Free Full Text]

52. Mansoor MA, Bergmark C, Svardal AM, Lonning PE, Ueland PM. Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease: homocysteine and peripheral vascular disease. Atheroscler Thromb Vasc Biol. 1995;15:232–240.[Abstract/Free Full Text]

53. Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol. 1996;143:845–859.[Abstract/Free Full Text]

54. Loehrer FM, Angst CP, Haefeli WE, Jordan PP, Ritz R, Fowler B. Low whole-blood S-adenosylmethionine and correlation between 5-methylenetetrahydrofolate and homocysteine in coronary artery disease. Arterioscler Thromb Vasc Biol. 1996;16:727–733.[Abstract/Free Full Text]

55. Lolin YI, Sanderson JE, Cheng SK, Chan CF, Pang CP, Woo KS, Masarei JR. Hyperhomocysteinemia and premature coronary artery disease in the Chinese. Heart. 1996;76:117–122.[Abstract/Free Full Text]

56. Gallagher PM, Meleady R, Shields DC, Tan KS, McMaster D, Rozen R, Evans A, Graham IM, Whitehead AS. Homocysteine and risk of premature coronary heart disease: evidence for a common gene mutation. Circulation. 1996;94:2154–2158.[Abstract/Free Full Text]

57. Malinow MR, Ducimetiere P, Luc G, Evans AE, Arveiler D, Cambien F, Upson BM. Plasma homocyst(e)ine levels and graded risk for myocardial infarction: findings in two populations at contrasting risk for coronary heart disease. Atherosclerosis. 1996;126:27–34.[Medline] [Order article via Infotrieve]

58. Kluijtmans LA, van den Heuvel LP, Boers GH, Frosst P, Stevens EM, van Oost BA, den Heijer M, Trijbels FJ, Rozen R, Blom HJ. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet. 1996;58:35–41.[Medline] [Order article via Infotrieve]

59. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Roulaud FM, Tan KS, Higgins I, Garcon D, Andria G, Medrano MJ, Candito M, Evans A. Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project. JAMA. 1997;277:1775–1781.[Abstract/Free Full Text]

60. Verhoef P, Kok FJ, Kruyssen DA, Schouten EG, Witteman JC, Grobbee DE, Ueland PM, Refsum H. Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 1997;17:989–995.[Abstract/Free Full Text]

61. Herzlich BC, Lichstein E, Schulhoff N, Weinstock M, Pagala M, Ravindran K, Namba T, Nieto FJ, Stabler SP, Allen RH, Malinow MR. Relationship among homocyst(e)ine, vitamin B-12 and cardiac disease in the elderly: association between vitamin B-12 deficiency and decreased left ventricle ejection fraction. J Nutr. 1996;126:1249S–1253S.

62. Munshi MN, Stone A, Fink L, Fonseca V. Hyperhomocyst(e)inemia following a methionine load in patients with non–insulin-dependent diabetes mellitus and macrovascular disease. Metabolism. 1996;45:133–135.[Medline] [Order article via Infotrieve]

63. Valentine RJ, Kaplan HS, Green R, Jacobsen DW, Myers SI, Clagett GP. Lipoprotein(a), homocysteine, and hypercoagulable states in young men with premature peripheral atherosclerosis: a prospective, controlled analysis. J Vasc Surg. 1996;23:53–63.

64. Lindgren A, Brattstrom L, Norrving B, Hultberg B, Andersson A, Johansson BB. Plasma homocysteine in the acute and convalescent phases after stroke. Stroke. 1995;26:795–800.[Abstract/Free Full Text]

65. Landgren F, Israelsson B, Lindgren A, Hultberg B, Andersson A, Brattstrom L. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med. 1995;237:381–388.[Medline] [Order article via Infotrieve]

66. Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet. 1995;346:1395–1398.[Medline] [Order article via Infotrieve]

67. Bostom AG, Shemin D, Verhoef P, Nadeau MR, Jacques PF, Selhub J, Dworkin L, Rosenberg IH. Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients: a prospective study. Arterioscler Thromb Vasc Biol. 1997;17:2554–2558.[Abstract/Free Full Text]

68. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997;337:230–236.[Abstract/Free Full Text]

69. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 1992;268:877–881.[Abstract/Free Full Text]

70. Wald NJ, Watt HC, Law MR, Weir DG, McPartlin J, Scott JM. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med. 1998;158:862–867.[Abstract/Free Full Text]

71. Verhoef P, Hennekens CH, Allen RH, Stabler SP, Willett WC, Stampfer MJ. Plasma total homocysteine and risk of angina pectoris with subsequent coronary artery bypass surgery. Am J Cardiol. 1997;79:799–801.[Medline] [Order article via Infotrieve]

72. Evans RW, Shaten BJ, Hempel JD, Cutler JA, Kuller LH. Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial. Arterioscler Thromb Vasc Biol. 1997;17:1947–1953.[Abstract/Free Full Text]

73. Verhoef P, Hennekens CH, Malinow MR, Kok FJ, Willett WC, Stampfer MJ. A prospective study of plasma homocysteine and risk of ischemic stroke. Stroke. 1994;25:1924–1930.[Abstract]

74. Alfthan G, Pekkanen J, Jauhiainen M, Pitkaniemi J, Karvonen M, Tuomilehto J, Salonen JT, Ehnholm C. Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis. 1994;106:9–19.[Medline] [Order article via Infotrieve]

75. Genest JJ Jr, McNamara JR, Salem DN, Wilson PW, Schaefer EJ, Malinow MR. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol. 1990;16:1114–1119.[Abstract]

76. Omenn GS, Beresford SA, Motulsky AG. Preventing coronary heart disease: B vitamins and homocysteine. Circulation. 1998;97:421–424.[Free Full Text]

77. Morrison HI, Schaubel D, Desmeules M, Wigle DT. Serum folate and risk of fatal coronary heart disease. JAMA. 1996;275:1893–1896.[Abstract/Free Full Text]

78. Malinow MR, Nieto FJ, Szklo M, Chambless LE, Bond G. Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults: the Atherosclerosis Risk in Communities Study. Circulation. 1993;87:1107–1113.[Abstract/Free Full Text]

79. Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PW, Belanger AJ, O'Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med. 1995;332:286–299.[Abstract/Free Full Text]

80. Gillman MW, Cupples LA, Gagnon D, Posner BM, Ellison RC, Castelli WP, Wolf PA. Protective effect of fruits and vegetables on development of stroke in men. JAMA. 1995;273:1113–1117.[Abstract/Free Full Text]

81. Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ. Folate and vitamin B₆ from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998;279:359–364.[Abstract/Free Full Text]

82. Tamura T. Bioavailability of folic acid in fortified food. Am J Clin Nutr. 1997;66:1299–1300.[Free Full Text]

83. Leveille GA, Zabik ME, Morgan KJ. Folacin, in Nutrients in Foods. Cambridge, Mass: The Nutrition Guild; 1983:I-23.

84. Food standards: amendment of the Standards of Identity for Enriched Grain Products to require addition of folic acid (21 CFR 136, 137, and 139). Federal Register. 1993;58(October 14):53305–53312.

85. Malinow MR, Kang SS, Taylor LM, Wong PW, Inahara T, Mukerjee D, Sexton G, Upson B. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation. 1989;79:1180–1188.[Abstract/Free Full Text]

86. Genest JJ Jr, McNamara JR, Upson B, Salem DN, Ordovas JM, Schaefer EJ, Malinow MR. Prevalence of familial hyperhomocyst(e)inemia in men with premature coronary artery disease. Arterioscler Thromb. 1991;11:1129–1136.[Abstract/Free Full Text]

87. Nedrebo BG, Ericsson UB, Nygard O, Refsum H, Ueland PM, Aakvaag A, Aanderud S, Lien EA. Plasma total homocysteine levels in hyperthyroid and hypothyroid patients. Metabolism. 1998;47:89–93.[Medline] [Order article via Infotrieve]

88. Arnadottir M, Hultberg B, Nilsson-Ehle P, Thysell H. The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. Scand J Clin Lab Invest. 1996;56:41–46.[Medline] [Order article via Infotrieve]

89. Petri M, Roubenoff R, Dallal GE, Nadeau MR, Selhub J, Rosenberg IH. Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. Lancet. 1996;348:1120–1124.[Medline] [Order article via Infotrieve]

90. Ermens AA, Refsum H, Rupreht J, Spijkers LJ, Guttormsen AB, Lindemans J, Ueland PM, Abels J. Monitoring cobalamin inactivation during nitrous oxide anesthesia by determination of homocysteine and folate in plasma and urine. Clin Pharmacol Ther. 1991;49:385–393.[Medline] [Order article via Infotrieve]

91. Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest. 1996;98:177–184.[Medline] [Order article via Infotrieve]

92. Refsum H, Helland S, Ueland PM. Fasting plasma homocysteine as a sensitive parameter of antifolate effect: a study on psoriasis patients receiving low-dose methotrexate treatment. Clin Pharmacol Ther. 1989;46:510–520.[Medline] [Order article via Infotrieve]

93. Allain P, LeBouil A, Cordillet E, LeQuay L, Bagheri H, Montastruc JL. Sulfate and cysteine levels in the plasma of patients with Parkinson's disease. Neurotoxicology. 1995;16:527–529.[Medline] [Order article via Infotrieve]

94. Peterson JC, Spence JD. Vitamins and progression of atherosclerosis in hyper-homocyst(e)inemia. Lancet. 1998;351:263. Letter.[Medline] [Order article via Infotrieve]

95. Chait A, Malinow MR, Resnick L, Oparil S, Nevin D, McCarron DA, Vanguard Study Group. A randomized control trial of the effects of a comprehensive risk reduction nutrition program on plasma homocysteine levels in hypertensives with associated cardiovascular risk factors. Am J Hypertens. 1996;9:16A. Abstract.

96. Cuskelly GJ, McNulty H, Scott JM. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. Lancet. 1996;347:657–659.[Medline] [Order article via Infotrieve]

97. Wilcken DE, Wilcken B, Dudman NP, Tyrrell PA. Homocystinuria: the effects of betaine in the treatment of patients not responsive to pyridoxine. N Engl J Med. 1983;309:448–453.[Abstract]

98. Bostom AG, Roubenoff R, Dellaripa P, Nadeau MR, Sutherland P, Wilson PW, Jacques PF, Selhub J, Rosenberg IH. Validation of abbreviated oral methionine-loading test. Clin Chem. 1995;41:948–949.[Free Full Text]

99. Bostom AG, Jacques PF, Nadeau MR, Williams RR, Ellison RC, Selhub J. Post-methionine load hyperhomocysteinemia in persons with normal fasting total plasma homocysteine: initial results from the NHLBI Family Heart Study. Atherosclerosis. 1995;116:147–151.[Medline] [Order article via Infotrieve]

100. Malinow MR, Stampfer MJ. Role of plasma homocyst(e)ine in arterial occlusive diseases. Clin Chem. 1994;40:857–858.[Free Full Text]

101. Stampfer MJ, Malinow MR. Can lowering homocysteine levels reduce cardiovascular risk? N Engl J Med. 1995;332:328–329.[Free Full Text]

This article has been cited by other articles:

				E. K. Song, Y.-J. Son, and T. A. Lennie Trait Anger, Hostility, Serum Homocysteine, and Recurrent Cardiac Events After Percutaneous Coronary Interventions Am. J. Crit. Care., November 1, 2009; 18(6): 554 - 561. [Abstract] [Full Text] [PDF]

				M.-L. Sung, C.-C. Wu, H.-I Chang, C.-K. Yen, H. J. Chen, J.-C. Cheng, S. Chien, and C.-N. Chen Shear Stress Inhibits Homocysteine-Induced Stromal Cell-Derived Factor-1 Expression in Endothelial Cells Circ. Res., October 9, 2009; 105(8): 755 - 763. [Abstract] [Full Text] [PDF]

				C. Antoniades, A. S. Antonopoulos, D. Tousoulis, K. Marinou, and C. Stefanadis Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials Eur. Heart J., January 1, 2009; 30(1): 6 - 15. [Abstract] [Full Text] [PDF]

				P.C. Bennett, S. Silverman, P.S. Gill, and G.Y.H. Lip Ethnicity and peripheral artery disease QJM, January 1, 2009; 102(1): 3 - 16. [Abstract] [Full Text] [PDF]

				Y. P. Liew, J. R. Bartholomew, S. Demirjian, J. Michaels, and M. J. Schreiber Jr. Combined Effect of Chronic Kidney Disease and Peripheral Arterial Disease on All-Cause Mortality in a High-Risk Population Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 1084 - 1089. [Abstract] [Full Text] [PDF]

				M. A. Medina Hyperhomocysteinemia and Occlusive Vascular Disease: An Emergent Role for Fibroblast Growth Factor 2 Circ. Res., April 25, 2008; 102(8): 869 - 870. [Full Text] [PDF]

				P.-Y. Chang, S.-C. Lu, C.-M. Lee, Y.-J. Chen, T. A. Dugan, W.-H. Huang, S.-F. Chang, W. S.L. Liao, C.-H. Chen, and Y.-T. Lee Homocysteine Inhibits Arterial Endothelial Cell Growth Through Transcriptional Downregulation of Fibroblast Growth Factor-2 Involving G Protein and DNA Methylation Circ. Res., April 25, 2008; 102(8): 933 - 941. [Abstract] [Full Text] [PDF]

				J. F. E. Mann, P. Sheridan, M. J. McQueen, C. Held, J. M. O. Arnold, G. Fodor, S. Yusuf, E. M. Lonn, and on behalf of the HOPE-2 investigators Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease--results of the renal Hope-2 study Nephrol. Dial. Transplant., February 1, 2008; 23(2): 645 - 653. [Abstract] [Full Text] [PDF]

				S. E. Chia, S. M. Ali, B. L. Lee, G. H. Lim, S. Jin, N.-V. Dong, N. T. H. Tu, C. N. Ong, and K. S. Chia Association of blood lead and homocysteine levels among lead exposed subjects in Vietnam and Singapore Occup. Environ. Med., October 1, 2007; 64(10): 688 - 693. [Abstract] [Full Text] [PDF]

				A. H. Lichtenstein, L. J. Appel, M. Brands, M. Carnethon, S. Daniels, H. A. Franch, B. Franklin, P. Kris-Etherton, W. S. Harris, B. Howard, et al. Summary of American Heart Association Diet and Lifestyle Recommendations Revision 2006 Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2186 - 2191. [Full Text] [PDF]

				J. A. Groner, M. Joshi, and J. A. Bauer Pediatric Precursors of Adult Cardiovascular Disease: Noninvasive Assessment of Early Vascular Changes in Children and Adolescents Pediatrics, October 1, 2006; 118(4): 1683 - 1691. [Abstract] [Full Text] [PDF]

				S. Kaul, A. A. Zadeh, and P. K. Shah Homocysteine Hypothesis for Atherothrombotic Cardiovascular Disease: Not Validated J. Am. Coll. Cardiol., September 5, 2006; 48(5): 914 - 923. [Abstract] [Full Text] [PDF]

				I. H. Rosenberg and C. D. Mulrow Trials that matter: should we routinely measure homocysteine levels and "treat" mild hyperhomocysteinemia? Ann Intern Med, August 1, 2006; 145(3): 226 - 227. [Full Text] [PDF]

				A. H. Lichtenstein, L. J. Appel, M. Brands, M. Carnethon, S. Daniels, H. A. Franch, B. Franklin, P. Kris-Etherton, W. S. Harris, B. Howard, et al. Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement From the American Heart Association Nutrition Committee Circulation, July 4, 2006; 114(1): 82 - 96. [Abstract] [Full Text] [PDF]

				R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]

				The Heart Outcomes Prevention Evaluation (HOPE) 2 Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease N. Engl. J. Med., April 13, 2006; 354(15): 1567 - 1577. [Abstract] [Full Text] [PDF]

				G. D.O. Lowe The association between elevated levels of inflammation biomarkers and coronary artery disease and death. Can. Med. Assoc. J., February 14, 2006; 174(4): 479 - 480. [Full Text] [PDF]

				D. Lairon, N. Arnault, S. Bertrais, R. Planells, E. Clero, S. Hercberg, and M.-C. Boutron-Ruault Dietary fiber intake and risk factors for cardiovascular disease in French adults Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1185 - 1194. [Abstract] [Full Text] [PDF]

				J. G. Dickhout, G. S. Hossain, L. M. Pozza, J. Zhou, S. Lhotak, and R. C. Austin Peroxynitrite Causes Endoplasmic Reticulum Stress and Apoptosis in Human Vascular Endothelium: Implications in Atherogenesis Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2623 - 2629. [Abstract] [Full Text] [PDF]

				G. Ravaglia, P. Forti, F. Maioli, L. Servadei, M. Martelli, N. Brunetti, L. Bastagli, D. Cucinotta, and E. Mariani Folate, But Not Homocysteine, Predicts the Risk of Fracture in Elderly Persons J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2005; 60(11): 1458 - 1462. [Abstract] [Full Text] [PDF]

				G. Ravaglia, P. Forti, F. Maioli, M. Martelli, L. Servadei, N. Brunetti, E. Porcellini, and F. Licastro Homocysteine and folate as risk factors for dementia and Alzheimer disease Am. J. Clinical Nutrition, September 1, 2005; 82(3): 636 - 643. [Abstract] [Full Text] [PDF]

				R. R. Calam, I. Mansoor, and J. Blaga Homocysteine Stability in Heparinized Plasma Stored in a Gel Separator Tube Clin. Chem., August 1, 2005; 51(8): 1554 - 1555. [Full Text] [PDF]

				A. H. Lichtenstein and R. M. Russell Essential Nutrients: Food or Supplements?: Where Should the Emphasis Be? JAMA, July 20, 2005; 294(3): 351 - 358. [Abstract] [Full Text] [PDF]

				T. C. Lee, J. G. Hanlon, J. Ben-David, G. L. Booth, W. J. Cantor, P. W. Connelly, and S. W. Hwang Risk Factors for Cardiovascular Disease in Homeless Adults Circulation, May 24, 2005; 111(20): 2629 - 2635. [Abstract] [Full Text] [PDF]

				E. A. Varga, A. C. Sturm, C. P. Misita, and S. Moll Homocysteine and MTHFR Mutations: Relation to Thrombosis and Coronary Artery Disease Circulation, May 17, 2005; 111(19): e289 - e293. [Full Text] [PDF]

				S. C. Smith Jr, R. V. Milani, D. K. Arnett, J. R. Crouse III, M. M. McDermott, P. M Ridker, R. S. Rosenson, K. A. Taubert, and P. W.F. Wilson Atherosclerotic Vascular Disease Conference: Writing Group II: Risk Factors Circulation, June 1, 2004; 109(21): 2613 - 2616. [Full Text] [PDF]

				K. Sydow, B. Hornig, N. Arakawa, S. M Bode-Boger, D. Tsikas, T. Munuzel, and R. H Boger Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia: potential role of ADMA Vascular Medicine, May 1, 2004; 9(2): 93 - 101. [Abstract] [PDF]

				M. Soinio, J. Marniemi, M. Laakso, S. Lehto, and T. Ronnemaa Elevated Plasma Homocysteine Level Is an Independent Predictor of Coronary Heart Disease Events in Patients with Type 2 Diabetes Mellitus Ann Intern Med, January 20, 2004; 140(2): 94 - 100. [Abstract] [Full Text] [PDF]

				H. Refsum, A. D. Smith, P. M. Ueland, E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek, J. Schneede, C. McPartlin, et al. Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion Clin. Chem., January 1, 2004; 50(1): 3 - 32. [Abstract] [Full Text] [PDF]

				G. S. Hossain, J. V. van Thienen, G. H. Werstuck, J. Zhou, S. K. Sood, J. G. Dickhout, A. B. L. de Koning, D. Tang, D. Wu, E. Falk, et al. TDAG51 Is Induced by Homocysteine, Promotes Detachment-mediated Programmed Cell Death, and Contributes to the Development of Atherosclerosis in Hyperhomocysteinemia J. Biol. Chem., August 8, 2003; 278(32): 30317 - 30327. [Abstract] [Full Text] [PDF]

				C. D. Morris and S. Carson Routine Vitamin Supplementation To Prevent Cardiovascular Disease: A Summary of the Evidence for the U.S. Preventive Services Task Force Ann Intern Med, July 1, 2003; 139(1): 56 - 70. [Abstract] [Full Text] [PDF]

				R. A. Kreisberg and A. Oberman Medical Management of Hyperlipidemia/Dyslipidemia J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2445 - 2461. [Full Text] [PDF]

				D. Girelli, N. Martinelli, F. Pizzolo, S. Friso, O. Olivieri, C. Stranieri, E. Trabetti, G. Faccini, E. Tinazzi, P. F. Pignatti, et al. The Interaction between MTHFR 677 C->T Genotype and Folate Status Is a Determinant of Coronary Atherosclerosis Risk J. Nutr., May 1, 2003; 133(5): 1281 - 1285. [Abstract] [Full Text] [PDF]

				Q. Shi, J. E. Savage, S. J. Hufeisen, L. Rauser, E. Grajkowska, P. Ernsberger, J. T. Wroblewski, J. H. Nadeau, and B. L. Roth L-Homocysteine Sulfinic Acid and Other Acidic Homocysteine Derivatives Are Potent and Selective Metabotropic Glutamate Receptor Agonists J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 131 - 142. [Abstract] [Full Text]

				M. Coffey, G. K. Crowder, and D. J. Cheek Reducing Coronary Artery Disease by Decreasing Homocysteine Levels Crit. Care Nurse, February 1, 2003; 23(1): 25 - 30. [Full Text] [PDF]

				J. Hung, J. P Beilby, M. W Knuiman, and M. Divitini Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia BMJ, January 18, 2003; 326(7381): 131 - 131. [Abstract] [Full Text] [PDF]

				References Circulation, December 17, 2002; 106(25): 3373 - 3421. [Full Text]

				C. D. Bushnell and L. B. Goldstein Homocysteine testing in patients with acute ischemic stroke Neurology, November 26, 2002; 59(10): 1541 - 1546. [Abstract] [Full Text] [PDF]

				P. W. F. Wilson Homocysteine and Coronary Heart Disease: How Great Is the Hazard? JAMA, October 23, 2002; 288(16): 2042 - 2043. [Full Text] [PDF]

				R. A Heuberger, A. I Fisher, P. F Jacques, R. Klein, B. E. Klein, M. Palta, and J. A Mares-Perlman Relation of blood homocysteine and its nutritional determinants to age-related maculopathy in the third National Health and Nutrition Examination Survey Am. J. Clinical Nutrition, October 1, 2002; 76(4): 897 - 902. [Abstract] [Full Text] [PDF]

				H. Adachi, Y. Hirai, Y. Fujiura, H. Matsuoka, A. Satoh, and T. Imaizumi Plasma Homocysteine Levels and Atherosclerosis in Japan: Epidemiological Study by Use of Carotid Ultrasonography Stroke, September 1, 2002; 33(9): 2177 - 2181. [Abstract] [Full Text] [PDF]

				S. Achenbach, D. Ropers, K. Pohle, A. Leber, C. Thilo, A. Knez, T. Menendez, R. Maeffert, M. Kusus, M. Regenfus, et al. Influence of Lipid-Lowering Therapy on the Progression of Coronary Artery Calcification: A Prospective Evaluation Circulation, August 27, 2002; 106(9): 1077 - 1082. [Abstract] [Full Text] [PDF]

				N. C.-K. Tan, N. Venketasubramanian, S.-M. Saw, and H. T.-L. Tjia Hyperhomocyst(e)inemia and Risk of Ischemic Stroke Among Young Asian Adults Stroke, August 1, 2002; 33(8): 1956 - 1962. [Abstract] [Full Text] [PDF]

				E. B. Feldman The Scientific Evidence for a Beneficial Health Relationship Between Walnuts and Coronary Heart Disease J. Nutr., May 1, 2002; 132(5): 1062S - 1101. [Abstract] [Full Text] [PDF]

				T. A. Pearson New Tools for Coronary Risk Assessment: What Are Their Advantages and Limitations? Circulation, February 19, 2002; 105(7): 886 - 892. [Abstract] [Full Text] [PDF]

				M.C. Verhaar, E. Stroes, and T.J. Rabelink Folates and Cardiovascular Disease Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 6 - 13. [Abstract] [Full Text] [PDF]

				N. Weiss, S. Heydrick, Y.-Y. Zhang, C. Bierl, A. Cap, and J. Loscalzo Cellular Redox State and Endothelial Dysfunction in Mildly Hyperhomocysteinemic Cystathionine {beta}-Synthase-Deficient Mice Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 34 - 41. [Abstract] [Full Text] [PDF]

				C. Fernandez-Miranda, M. Sanz, A. de la Calle, C. Loinaz, P. Gomez, P. Diaz-Rubio, A. G. de la Camara, and E. Moreno Determinants of Increased Plasma Homocysteine in 221 Stable Liver Transplant Patients Clin. Chem., November 1, 2001; 47(11): 2037 - 2040. [Full Text] [PDF]

				N. Weiss, Y.-Y. Zhang, S. Heydrick, C. Bierl, and J. Loscalzo Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction PNAS, October 12, 2001; (2001) 231428998. [Abstract] [Full Text] [PDF]

				T. Mueller, B. Furtmueller, J. Aigelsdorfer, C. Luft, W. Poelz, and M. Haltmayer Total serum homocysteine - a predictor of extracranial carotid artery stenosis in male patients with symptomatic peripheral arterial disease Vascular Medicine, August 1, 2001; 6(3): 163 - 167. [Abstract] [PDF]

				P. Knekt, A. Reunanen, G. Alfthan, M. Heliovaara, H. Rissanen, J. Marniemi, and A. Aromaa Hyperhomocystinemia: A Risk Factor or a Consequence of Coronary Heart Disease? Arch Intern Med, July 9, 2001; 161(13): 1589 - 1594. [Abstract] [Full Text] [PDF]

				M. R. Fokkema, J. M. Weijer, D.A. J. Dijck-Brouwer, J. J. van Doormaal, and F. A.J. Muskiet Influence of Vitamin-optimized Plasma Homocysteine Cutoff Values on the Prevalence of Hyperhomocysteinemia in Healthy Adults Clin. Chem., June 1, 2001; 47(6): 1001 - 1007. [Abstract] [Full Text] [PDF]

				P. M. Ridker, M. J. Stampfer, and N. Rifai Novel Risk Factors for Systemic Atherosclerosis: A Comparison of C-Reactive Protein, Fibrinogen, Homocysteine, Lipoprotein(a), and Standard Cholesterol Screening as Predictors of Peripheral Arterial Disease JAMA, May 16, 2001; 285(19): 2481 - 2485. [Abstract] [Full Text] [PDF]

				P. M. Ridker High-Sensitivity C-Reactive Protein : Potential Adjunct for Global Risk Assessment in the Primary Prevention of Cardiovascular Disease Circulation, April 3, 2001; 103(13): 1813 - 1818. [Abstract] [Full Text] [PDF]

				S. R. Lentz, D. J. Piegors, M. R. Malinow, and D. D. Heistad Supplementation of Atherogenic Diet With B Vitamins Does Not Prevent Atherosclerosis or Vascular Dysfunction in Monkeys Circulation, February 20, 2001; 103(7): 1006 - 1011. [Abstract] [Full Text] [PDF]

				L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al. Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Circulation, January 2, 2001; 103(1): 163 - 182. [Full Text] [PDF]

				L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al. Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Stroke, January 1, 2001; 32(1): 280 - 299. [Full Text] [PDF]

				R. M. Krauss, R. H. Eckel, B. Howard, L. J. Appel, S. R. Daniels, R. J. Deckelbaum, J. W. Erdman Jr, P. Kris-Etherton, I. J. Goldberg, T. A. Kotchen, et al. AHA Scientific Statement: AHA Dietary Guidelines: Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association J. Nutr., January 1, 2001; 131(1): 132 - 146. [Full Text]

				B. K. Nallamothu, A. M. Fendrick, M. Rubenfire, S. Saint, R. R. Bandekar, and G. S. Omenn Potential Clinical and Economic Effects of Homocyst(e)ine Lowering Arch Intern Med, December 11, 2000; 160(22): 3406 - 3412. [Abstract] [Full Text] [PDF]

				R. M. Krauss, R. H. Eckel, B. Howard, L. J. Appel, S. R. Daniels, R. J. Deckelbaum, J. W. Erdman Jr, P. Kris-Etherton, I. J. Goldberg, T. A. Kotchen, et al. AHA Dietary Guidelines : Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association Stroke, November 1, 2000; 31(11): 2751 - 2766. [Full Text] [PDF]

				R. M. Krauss, R. H. Eckel, B. Howard, L. J. Appel, S. R. Daniels, R. J. Deckelbaum, J. W. Erdman Jr, P. Kris-Etherton, I. J. Goldberg, T. A. Kotchen, et al. AHA Dietary Guidelines : Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association Circulation, October 31, 2000; 102(18): 2284 - 2299. [Full Text] [PDF]

				S. R. Lentz, R. A. Erger, S. Dayal, N. Maeda, M. R. Malinow, D. D. Heistad, and F. M. Faraci Folate dependence of hyperhomocysteinemia and vascular dysfunction in cystathionine beta -synthase-deficient mice Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H970 - H975. [Abstract] [Full Text] [PDF]

				K. Willcutts and J. S. Minasi Use of B Vitamins to Reduce Homocysteine in Chronic Mesenteric Ischemia Nutr Clin Pract, August 1, 2000; 15(4): 171 - 173. [Abstract] [PDF]

				G. L. Booth, E. E.L. Wang, and with the Canadian Task Force on Preventive Health Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events Can. Med. Assoc. J., July 1, 2000; 163(1): 21 - 29. [Abstract] [Full Text] [PDF]

				J. Genest Jr., M.-C. Audelin, and E. Lonn Homocysteine: To screen and treat or to wait and see? Can. Med. Assoc. J., July 1, 2000; 163(1): 37 - 38. [Full Text] [PDF]

				M. F. Picciano Is homocysteine a biomarker for identifying women at risk of complications and adverse pregnancy outcomes? Am. J. Clinical Nutrition, April 1, 2000; 71(4): 857 - 858. [Full Text] [PDF]

				K. ROBINSON Homocysteine, B vitamins, and risk of cardiovascular disease Heart, February 1, 2000; 83(2): 127 - 130. [Full Text]

				S. M. Grundy, T. Bazzarre, J. Cleeman, R. B. D’Agostino Sr, M. Hill, N. Houston-Miller, W. B. Kannel, R. Krauss, H. M. Krumholz, R. M. Lauer, et al. Prevention Conference V : Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Medical Office Assessment : Writing Group I Circulation, January 4, 2000; 101 (1): e3 - e11. [Full Text] [PDF]

				M. Cattaneo, M. R. Malinow, A. G. Bostom, and R. M. Krauss Homocysteine and Cardiovascular Diseases • Response Circulation, December 21, 1999; 100 (25): e151 - e151. [Full Text] [PDF]

				Assessment of Laboratory Tests for Plasma Homocysteine--Selected Laboratories, July-September 1998 JAMA, December 8, 1999; 282(22): 2112 - 2113. [Full Text] [PDF]

				B. N. Ames Cancer prevention and diet: Help from single nucleotide polymorphisms PNAS, October 26, 1999; 96(22): 12216 - 12218. [Full Text] [PDF]

				S. M. Grundy, R. Pasternak, P. Greenland, S. Smith Jr, and V. Fuster Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1348 - 1359. [Full Text] [PDF]

				L. A. Bortolotto, M. E. Safar, E. Billaud, C. Lacroix, R. Asmar, G. M. London, and J. Blacher Plasma Homocysteine, Aortic Stiffness, and Renal Function in Hypertensive Patients Hypertension, October 1, 1999; 34(4): 837 - 842. [Abstract] [Full Text] [PDF]

				S. M. Grundy, R. Pasternak, P. Greenland, S. Smith Jr, and V. Fuster Assessment of Cardiovascular Risk by Use of Multiple-Risk-Factor Assessment Equations : A Statement for Healthcare Professionals From the American Heart Association and the American College of Cardiology Circulation, September 28, 1999; 100(13): 1481 - 1492. [Full Text] [PDF]

				S. M. Grundy Primary Prevention of Coronary Heart Disease : Integrating Risk Assessment With Intervention Circulation, August 31, 1999; 100(9): 988 - 998. [Full Text] [PDF]

				A. G. Bostom and J. Selhub Homocysteine and Arteriosclerosis : Subclinical and Clinical Disease Associations Circulation, May 11, 1999; 99(18): 2361 - 2363. [Full Text] [PDF]

				A. G. BOSTOM and B. F. CULLETON Hyperhomocysteinemia in Chronic Renal Disease J. Am. Soc. Nephrol., April 1, 1999; 10(4): 891 - 900. [Full Text]

				A. Undas, E. B. Williams, S. Butenas, T. Orfeo, and K. G. Mann Homocysteine Inhibits Inactivation of Factor Va by Activated Protein C J. Biol. Chem., February 2, 2001; 276(6): 4389 - 4397. [Abstract] [Full Text] [PDF]

				N. Weiss, Y.-Y. Zhang, S. Heydrick, C. Bierl, and J. Loscalzo Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction PNAS, October 23, 2001; 98(22): 12503 - 12508. [Abstract] [Full Text] [PDF]

				P. M. Ridker, J. Shih, T. J. Cook, M. Clearfield, J. R. Downs, A. D. Pradhan, S. E. Weis, A. M. Gotto Jr, and for the Air Force/Texas Coronary Atherosclerosis P Plasma Homocysteine Concentration, Statin Therapy, and the Risk of First Acute Coronary Events Circulation, April 16, 2002; 105(15): 1776 - 1779. [Abstract] [Full Text] [PDF]

This Article Free upon publication Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Malinow, M. R. Articles by Krauss, R. M. Search for Related Content PubMed PubMed Citation Articles by Malinow, M. R. Articles by Krauss, R. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Diets Vitamins Related Collections AHA Statements and Guidelines