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P F Jacques

Publications and source records attributed to P F Jacques.

At least 55 records · Page 3Linked to original sources
PubMed1999

The potential preventive effects of vitamins for cataract and age-related macular degeneration.

Age-related cataract and age-related macular degeneration (AMD) are important public health problems. Approximately 50% of the 30 to 50 million cases of blindness worldwide result from unoperated cataract. In the US and other developed countries AMD is the leading cause of blindness, but age-related cataract remains the leading cause of visual disability. Age-related cataract and AMD represent an enormous economic burden. In the United States more than 1.3 million cataract extractions are performed annually at a cost of approximately $3.5 billion. Much of the experimental research on the etiology of cataract and AMD has focused on the role of nutritional antioxidants (vitamin C, vitamin E, and carotenoids). Evidence from epidemiologic studies support a role for nutritional antioxidants in delaying the onset of these age-related vision disorders. Although it is not yet possible to conclude that antioxidant nutrients have a role in prevention of cataract or AMD, a summary of the epidemiologic evidence suggests that it is prudent to consume diets high in vitamins C and E and carotenoids, particularly the xanthophylls, as insurance against the development of cataract and AMD.

Antioxidants↗
PubMed1999

Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey.

BACKGROUND: The elevation of circulating total homocysteine concentrations in a fasting state is associated with an increased risk of occlusive vascular disease. OBJECTIVE: The primary goals of this study were to describe the distribution of serum total homocysteine concentrations in the United States and to test for differences in homocysteine concentrations among sex, age, and race-ethnicity categories. DESIGN: Using surplus sera from phase 2 of the third National Health and Nutrition Examination Survey, we measured serum total homocysteine concentrations for a nationally representative sample of 3766 males and 4819 females aged > or = 12 y. RESULTS: Age-adjusted geometric mean total homocysteine concentrations were 9.6 and 7.9 mmol/L in non-Hispanic white males and females, 9.8 and 8.2 mmol/L in non-Hispanic black males and females, and 9.4 and 7.4 mmol/L in Mexican American males and females, respectively. Age-adjusted geometric mean total homocysteine concentrations were significantly lower in females than in males in each race-ethnicity group (P < 0.01) and were significantly lower in Mexican American females than in non-Hispanic white and non-Hispanic black females (P < 0.01). There was a significant age-sex interaction (P < 0.01), reflecting the fact that homocysteine concentrations in females tended to diverge from those in males at younger ages and converge with those in males at older ages. CONCLUSIONS: The first data on homocysteine concentrations in a nationally representative sample of Americans confirm the age and sex differences reported previously in nonrepresentative samples. These data also indicate that differences between Mexican American and non-Hispanic females may influence circulating homocysteine concentrations.

Adolescent↗
PubMed1999

Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients.

The mild fasting hyperhomocysteinemia commonly observed in chronic (ie, >/=6 months posttransplantation) renal transplant recipients (RTRs) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid. There are no controlled data evaluating the comparative efficacy of supraphysiological versus standard multivitamin dose folic acid supplementation in reducing fasting total homocysteine (tHcy) levels among RTRs. We block-randomized 60 chronic, stable RTRs on the basis of their screening fasting tHcy level to 3 groups of 20 subjects treated for 12 weeks with folic acid at either 2.4 (group 1), 0.4 (ie, standard multivitamin dose) (group 2), or 0.0 (group 3) mg/d. All 60 study participants also received 50 mg/d vitamin B(6) and 0.4 mg/d vitamin B(12). The mean percent reductions (+/-SEM) in fasting tHcy were as follows: group 1, 32.3+/-2.4%; group 2, 23.4+/-2.3%; and group 3, 19.1+/-2.3%. ANCOVA accounting for the pretreatment matching and adjusted for pretreatment levels of fasting tHcy, folate, and albumin; change in creatinine during the study; and cyclosporine A use revealed significant overall group differences (P=0.005) and significant differences between groups 1 and 2 (P=0. 038) and groups 1 and 3 (P=0.001), but not between groups 2 and 3 (P=0.153). Moreover, a chi(2) analysis of participants with pretreatment tHcy levels >/=15 micromol/L (n=29) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels <12 micromol/L: group 1, 5 of 10 (50%); group 2, 1 of 11 (9%); and group 3, 0 of 8 (0%) (P=0.016; test of trend P=0. 007). We conclude that a supraphysiological dose of folic acid is superior to standard multivitamin dosing for the reduction of fasting tHcy levels in chronic RTRs.

Adult↗
PubMed1999

Cystatin C as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine.

Serum creatinine, a surrogate for both renal function and homocysteine generation, is a determinant of fasting plasma total homocysteine levels in coronary artery disease (CAD) patients. We hypothesized that among stable-CAD patients with normal creatinine levels (ie, </=1.4 mg/dL), serum cystatin C, a more sensitive indicator of glomerular filtration rate, would better predict fasting total homocysteine levels in comparison with serum creatinine. Fasting plasma total homocysteine, folate, vitamin B(12), and pyridoxal 5'-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 164 consecutive stable-CAD patients (mean+/-SD age, 61+/-9 years; 78.7% men) whose serum creatinine level was </=1.4 mg/dL. All subjects were examined at least 3 to 4 months after the widespread availability of cereal grain flour products fortified with folic acid. General linear modeling with ANCOVA revealed that serum cystatin C (P<0.001), B(12) (P<0.001), age (P=0.002), albumin (P=0.008), and sex (P=0.024) were independent determinants of fasting total homocysteine levels. Cystatin C alone determined over half of the variability (ie, R(2)) in total homocysteine levels accounted for by these 5 independent regressors. In contrast, creatinine, folate, and pyridoxal 5'-phosphate were not independently predictive of fasting total homocysteine levels (P>0.2). Consistent with the impact of folic acid fortification of cereal grain flour in the general population, only 1 of the CAD subjects (0.6%) had a plasma folate level <3 ng/mL. We conclude that serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable-CAD patients with normal serum creatinine.

Adult↗
PubMed1999

Serum cystatin C as a determinant of fasting total homocysteine levels in renal transplant recipients with a normal serum creatinine.

Serum creatinine, a surrogate for both renal function and homocysteine generation, is an important determinant of fasting plasma total homocysteine levels in stable renal transplant recipients. In this study, it is hypothesized that among stable renal transplant recipients with normal creatinine levels (i.e., < or = 1.5 mg/dl), serum cystatin C, a more sensitive indicator of GFR, would better predict fasting total homocysteine levels compared with serum creatinine. Fasting plasma total homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 28 consecutive renal transplant recipients (mean age 47 +/- 14 yr; 60.7% men) with stable allograft function, whose serum creatinine was < or = 1.5 mg/dl. General linear modeling with analysis of covariance revealed that serum cystatin C was independently predictive (partial R = 0.494; P = 0.023) of fasting total homocysteine levels after adjustment for age, gender, vitamin status, albumin, and creatinine levels. In contrast, creatinine levels were not predictive of fasting total homocysteine levels in this model (P = 0.110) or an identical model that excluded cystatin C (P = 0.131). Serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable renal transplant recipients with a normal serum creatinine.

Adult↗
PubMed1998

Dietary determinants of iron stores in a free-living elderly population: The Framingham Heart Study.

Epidemiologic studies have found a relation between body iron stores and risk of chronic disease. Iron-absorption studies from single meals have shown that many dietary factors can influence nonheme-iron bioavailability. However, little is known about the association of these dietary factors with iron stores in free-living elderly populations. To address this question, we investigated the consumption of various dietary components and iron stores in an elderly sample of The Framingham Heart Study participants. Serum ferritin was used as a measure of body iron stores in 634 free-living elderly (67-93 y of age), and dietary intake during the previous year was assessed by a food-frequency questionnaire. The relation between serum ferritin and various dietary factors was assessed by multiple regression analysis. Subjects whose ferritin concentrations might be pathologically elevated because of infection, inflammation, liver disease, or genetic hemochromatosis were excluded from the analysis. After we controlled for sex, age, body mass index, total energy intake, smoking, and use of aspirin and other medications known to affect blood loss, we found five significant dietary factors associated with iron stores. Heme iron, supplemental iron, dietary vitamin C, and alcohol were positively associated with serum ferritin, whereas coffee intake had a negative association. As expected, sex was a strong predictor of serum ferritin-women having significantly lower mean concentrations than men. However, age was not related to serum ferritin in our elderly population. Our results suggest that in typical Western-style diets, a small number of dietary factors probably modulate the bioavailability of dietary iron and influence the accumulation of iron stores.

Adult↗
PubMed1997

Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial.

BACKGROUND: Stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, which is a risk factor for arteriosclerosis. OBJECTIVE: To determine the effect of treatment with 1) vitamin B6 or 2) folic acid plus vitamin B12 on fasting and post-methionine-loading plasma total homocysteine levels in renal transplant recipients. DESIGN: Block-randomized, placebo-controlled, 2 x 2 factorial study. SETTING: University-affiliated transplantation program. PATIENTS: 29 clinically stable renal transplant recipients. INTERVENTION: Patients were randomly assigned to one of four regimens: placebo (n = 8); vitamin B6, 50 mg/d (n = 7); folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7); or vitamin B6, 50 mg/d, folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7). MEASUREMENTS: Fasting and 2-hour post-methionine-loading plasma total homocysteine levels. RESULTS: Vitamin B6 treatment resulted in a 22.1% reduction in geometric-mean post-methionine-loading increases in plasma total homocysteine levels (P = 0.042), and folic acid plus vitamin B12 treatment caused a 26.2% reduction in geometric-mean fasting plasma total homocysteine levels (P = 0.027). These results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine. CONCLUSIONS: Vitamin B6 should be added to the combination of folic acid and vitamin B12 for effective reduction of both post-methionine-loading and fasting plasma total homocysteine levels in renal transplant recipients.

Drug Therapy, Combination↗
PubMed1997

Nutrition Screening Initiative Checklist may be a better awareness/educational tool than a screening one.

OBJECTIVE: To evaluate the Nutrition Screening Initiative (NSI) checklist as a screening and an awareness/educational tool in an elderly population. DESIGN: Epidemiologic follow-up study. Information similar to the questions of the NSI checklist was collected by the Nutrition Status Survey of Boston elders between 1981 and 1984. Vital status of volunteers was obtained during 8 to 12 years of follow-up. SUBJECTS/SETTING: Community-dwelling men (n = 200) and women (n = 381) aged 60 years and older who participated in the survey. STATISTICAL ANALYSES PERFORMED: Multivariate analysis was used to assess the association between mortality and each of the NSI-similar questions and the cumulative score, which is the sum of the values assigned to each question. Attributable risk percent, a measure of association, was calculated to measure the percentage of deaths that could potentially be prevented if the risk factors or their consequences were eliminated. RESULTS: Eating meals alone, problems biting or chewing, difficulties with shopping or cooking, and taking more than three medications per day were positively associated with mortality (P < .05). The cumulative score, although significant, was a weaker predictor of mortality. Attributable risk percent of mortality was 19.9% and 51.2% for men and women, respectively. APPLICATIONS/CONCLUSIONS: Some but not all of the individual questions of the NSI checklist equivalent were significantly associated with mortality and identify specific problems that may have a long-term negative effect yet may be missed if the cumulative score were the sole criterion for screening people. The attributable risk percent suggests that the checklist may be best used as an awareness/educational tool as intended originally and could have an important public health effect on early death of community-dwelling elderly people.

Aged↗
PubMed1997

Vitamin C in human and guinea pig aqueous, lens and plasma in relation to intake.

PURPOSE: Given the recent correlation between nutrition and risk for eye disease, there is keen interest in a possible correlation between nutrient intake and eye-tissue nutrient levels. In this work, the objective was (1) to determine, for the first time, the relation between dietary intake of vitamin C and eye tissue levels of the vitamin in free-living humans, (2) to determine the relation between levels of the vitamin in plasma, lens and aqueous, and (3) to compare this information to data gathered for a carefully reared group of guinea pigs that were fed different levels of vitamin C. METHODS: Two hundred sixty-five cataract patients (mean age = 72 years) from a clinical practice were recruited for this study. One hundred thirty-two patients provided the dietary intake data via a food frequency questionnaire, which we used for this work. Plasma, aqueous humor, and lens samples were obtained at the time of lentectomy and preserved for vitamin C analysis. Comparable samples were obtained from male Hartley white guinea pigs that were fed known amounts of vitamin C. Linear and log10-linear statistical models were also used to characterize the relation between vitamin C intake and human ocular tissue levels of the vitamin and to examine potential confounding and the effect of modification by age and sex. RESULTS: In humans, plasma and aqueous vitamin C concentrations were related to intake in a log-linear fashion, with slopes of 0.03 mM plasma vitamin C/log10-mg daily vitamin C intake and 0.41 mM aqueous vitamin C/log10-mg daily vitamin C intake. The best fit of vitamin C levels in lens and diet predicts a linear relationship with a sex-adjusted slope of 0.00094 mM lens vitamin C/mg daily vitamin C intake, although a log-linear relation can also be modeled. In guinea pigs, diet was related to eye tissue and plasma levels of the vitamin by a log10 linear relationship in all cases. Vitamin C in human lens was linearly related to plasma and aqueous vitamin C with slopes of 8.8 and 0.23, respectively. Vitamin C in aqueous was related to plasma in a log10-linear fashion with a slope of 1.6 mM aqueous vitamin C/log10 mM plasma vitamin C. In guinea pigs, vitamin C in plasma was related to aqueous and lens vitamin C by log10-linear relationships, whereas lens and aqueous vitamin C were clearly linearly related. CONCLUSIONS: Plasma and aqueous appear to be saturated in humans with intakes of < 250 mg vitamin C/day. However, a saturating relationship between lens vitamin C and dietary intake in humans was not indicated in this study, although such a relationship is seen in guinea pigs. Intertissue relations between vitamin C levels in humans and guinea pigs are similar for some but not all relations.

Adult↗
PubMed1997

Long-term vitamin C supplement use and prevalence of early age-related lens opacities.

We designed the present study to examine the cross-sectional relation between age-related lens opacities and vitamin C supplement use over a 10-12-y period before assessment of lens status in women without diagnosed cataract or diabetes. This design avoids biased measurement of nutrient intake that results when knowledge of lens opacities influences nutrition-related behavior or its reporting. The participants were 247 Boston-area women aged 56-71 y selected from the Nurses' Health Study cohort with oversampling of women with high or low vitamin C intakes. Lens opacities were graded with the Lens Opacification Classification System II. Use of vitamin C supplements for > or = 10 y (n = 26) was associated with a 77% lower prevalence of early lens opacities (odds ratio: 0.23; 95% CI: 0.09, 0.60) at any lens site and a 83% lower prevalence of moderate lens opacities (odds ratio: 0.17; 95% CI: 0.03, 0.85) at any lens site compared with women who did not use vitamin C supplements (n = 141) after adjustment for age and other potentially confounding variables. Women who consumed vitamin C supplements for < 10 y showed no evidence of a reduced prevalence of early opacities. These data, together with data from earlier experimental and epidemiologic studies, suggest that long-term consumption of vitamin C supplements may substantially reduce the development of age-related lens opacities.

Adult↗
PubMed1997

Plasma 25-hydroxyvitamin D and its determinants in an elderly population sample.

This study describes the distribution and determinants of plasma 25-hydroxyvitamin D [25(OH)D] concentrations and risk factors for low 25(OH)D (< or = 37.5 nmol/L) in 290 men and 469 women aged 67-95 y who were in the Framingham Heart Study cohort. Mean (+/-SD) 25(OH)D concentrations were 82 +/- 29 nmol/L in men and 71 +/- 29 nmol/L in women. 25(OH)D was low in 6.2% of men and 14.5% of women. 25(OH)D concentrations were strongly associated with season of examination, inversely associated with time spent indoors and body mass index, and positively associated with dietary vitamin D intake. In women, concentrations were also inversely associated with age and positively associated with supplemental vitamin D intake and residence for > or = 3 mo/y in Florida, California, or Arizona, and in men were positively associated with serum creatinine concentrations. Similar amounts of variance in 25(OH)D concentrations were explained by vitamin D intake and sunlight exposure, the former being more important in women and the latter in men. None of the known or suspected determinants of vitamin D status could explain the lower 25(OH)D concentrations in women, but the sex difference was not seen for individuals examined during the winter. Results from this population-based sample of elderly individuals suggest that inadequate vitamin D status is an important public health problem, which could be readily addressed by adequate vitamin D intake or sunlight exposure.

Age Factors↗
PubMed1997

Excess prevalence of fasting and postmethionine-loading hyperhomocysteinemia in stable renal transplant recipients.

Hyperhomocysteinemia, either fasting or after methionine loading, may contribute to the increased incidence of cardiovascular disease events experienced by renal transplant recipients. Limited data are available on fasting homocysteine (Hcy) levels, and none on postmethionine-loading Hcy levels, in these patients. We assessed the prevalence and potential determinants of fasting and postmethionine-loading hyperhomocysteinemia in 29 stable renal transplant recipients and 58 age- and sex-matched, population-based controls free of renal disease with serum creatinine levels of 1.5 mg/dL or less. Total (t) plasma Hcy was determined fasting and 2 hours after methionine loading, along with fasting determinations of the B-vitamin cofactors/substrates for Hcy metabolism, ie, pyridoxal 5'-phosphate, B-12, and folate and serum creatinine. Geometric mean fasting (18.1 versus 9.8 microM, P < .001) and postmethionine-loading increase (22.0 versus 15.2, P = .001) in tHcy levels were significantly greater in the renal transplant recipients, as were the prevalence odds (with 95% confidence intervals) for fasting [14.8 (3.4-64.7)], postmethionine loading [6.9 (1.5-32.8)], combined fasting and postmethionine-loading [18.0 (2.3-142.1)] hyperhomocysteinemia, and inadequate circulating folate [4.2 (1.1-16.5)] or pyridoxal 5'-phosphate [3.2 (0.9-11.0) status. Correlation analyses suggested important potential relationships between creatinine and both fasting (+0.64, P < .001) and postmethionine-load increase (+0.38, P = .045) in tHcy, folate and fasting (-0.41, P = .025) tHcy, and pyridoxal 5'-phosphate and postmethionine-loading increase (-0.33, P = .091) in tHcy. We conclude that there is an excess prevalence of fasting and postmethionine-loading hyperhomocysteinemia in stable renal transplant recipients. Renal function is related to both fasting and postmethionine loading-hyperhomocysteinemia, inadequate folate status is associated with fasting hyperhomocysteinemia, and inadequate vitamin B-6 status may be related to postmethionine-loading hyperhomocysteinemia in this patient population.

Adult↗
PubMed1997

Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients. A prospective study.

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.

Adult↗
PubMed1996

Carotenoids, vitamins C and E, and mortality in an elderly population.

In 1981-1984, the nutritional status of 747 noninstitutionalized Massachusetts residents aged 60 years and over was assessed. Nine to 12 years later, the vital status of these subjects was determined. The data of a subset of 725 community-dwelling volunteers was used to examine associations between mortality and the nutrient antioxidants (carotenoids and vitamins C and E) in plasma, diet, and supplements. Results indicated that subjects with plasma vitamin C levels in the middle and high quintiles had a lower overall mortality (relative risk (RR) = 0.64, 95% confidence interval (CI) 0.44-0.94 and RR = 0.54, 95% CI 0.32-0.90, respectively) than those in the lowest quintile even after adjustment for potential confounders. These associations were largely due to reduced mortality from heart disease. Subjects in the highest quintile of total intake of vitamin C also had a significantly lower risk of overall mortality (RR = 0.55, 95% CI 0.32-0.93) and mortality from heart disease (RR = 0.38, 95% CI 0.19-0.75) than did those in the lowest quintile after potential confounders were controlled for. Intake of vegetables was inversely associated with overall mortality (p for trend = 0.003) and mortality from heart disease (p for trend = 0.04). No other significant associations were observed. In conclusion, the results indicate that high intakes and plasma levels of vitamin C and frequent consumption of vegetables may be protective against early mortality and mortality from heart disease.

Age Distribution↗
PubMed1996

Hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) excess in maintenance dialysis patients: a matched case-control study.

Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poorly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) Lp(a)) excess, and combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, in maintenance dialysis patients. Fasting total plasma homocysteine (Hcy), fibrinogen, Lp(a), glucose, and total and HDL cholesterol levels, and traditional CVD risk factor (i.e. glucose tolerance, smoking, hypertension, dyslipidemia) prevalences were assessed in 71 dialysis patients and 71 age, sex, and race matched Framingham Study controls free of clinical renal disease, with normal serum creatinine (< or = 1.5 mg/dl). Mean plasma Hcy 23.7 vs. 9.9 microM, P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/dl, P = 0.0070) levels were substantially increased in the dialysis patients. Matched odds ratios (with 95% confidence intervals), dialysis patients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia, 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35.0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incidence of vascular disease sequelae experienced by dialysis patients, which is inadequately explained by traditional CVD risk factors. Controlled, prospective studies of well-characterized maintenance dialysis cohorts are urgently required to substantiate this hypothesis.

Adult↗
PubMed1996

Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate, the major carbon donor in remethylation of homocysteine to methionine. A common MTHFR mutation, an alanine-to-valine substitution, renders the enzyme thermolabile and may cause elevated plasma levels of the amino acid homocysteine. METHODS AND RESULTS: To assess the potential interaction between this mutation and vitamin coenzymes in homocysteine metabolism, we screened 365 individuals from the NHLBI Family Heart Study. Among individuals with lower plasma folate concentrations ( < 15.4 nmol/L), those with the homozygous mutant genotype had total fasting homocysteine levels that were 24% greater (P<.05) than individuals with the normal genotype. A difference between genotypes was not seen among individuals with folate levels > or = 15.4 nmol/L. CONCLUSIONS: Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocysteine concentrations; folate supplementation may be necessary to prevent fasting hyperhomocysteinemia in such persons.

Adult↗
PubMed1996

Folate status is the major determinant of fasting total plasma homocysteine levels in maintenance dialysis patients.

Limited data are available on the determinants of homocysteinemia or the association between plasma homocysteine (Hcy) levels and prevalent cardiovascular disease (CVD) in maintenance dialysis patients. We assessed etiology of renal failure, residual renal function and dialysis adequacy-related variables, and vitamin status, as determinants of fasting total plasma homocysteine (Hcy) in 75 maintenance dialysis patients. We also assessed the potential interactive effect on plasma Hcy of folate status and a common mutation (ala to val; homozygous val-val frequency approximately 10%) in methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme crucial for the remethylation of homocysteine (Hcy) to methionine. Lastly, we evaluated whether the Hcy levels differed amongst these patients in the presence or absence of prevalent CVD, after adjustment for the traditional CVD risk factors. Fasting total plasma Hcy, folate, pyridoxal 5'-phosphate (PLP; active B6), B12, creatinine, glucose, total and HDL cholesterol levels, and presence of the ala to val MTHFR mutation were determined, and clinical CVD and CVD risk factor prevalence were ascertained. General linear modelling/analysis of covariance revealed: (1) folate status and serum creatinine were the only significant independent predictors of fasting Hcy; (2) there was a significant interaction between presence of the val mutation and folate status, i.e., among patients with plasma folate below the median (< 29.2 ng/ml), geometric mean Hcy levels were 33% greater (29.0 vs. 21.8 microM, P = 0.012) in the pooled homozygotes (val-val) and heterozygotes (ala-val) for the ala to val mutation, vs. normals (ala-ala); (3) there was no association between prevalent CVD and plasma Hcy. Given potentially intractable survivorship effects, prospective cohort studies will be required to clarify the relationship between plasma Hcy or any putative CVD risk factor, and incident CVD in dialysis patients. If a positive association between plasma Hcy and incident CVD can be established in maintenance dialysis patients, the current data provide a rationale for additional folic acid supplementation in this patient population.

Adult↗