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Biomedical subjects

P F Jacques

Publications and source records attributed to P F Jacques.

At least 19 recordsLinked to original sources
PubMed2005

Phylloquinone intake as a marker for coronary heart disease risk but not stroke in women.

OBJECTIVE: To examine the feasibility of using phylloquinone intake as a marker for coronary heart disease (CHD) and stroke risk in women. DESIGN AND SETTING: Nurses' Health Study, a prospective cohort study during 1984-2000. Dietary data were collected in 1984, 1986, 1990, and 1994 using a validated semiquantitative food frequency questionnaire. SUBJECTS: A total of 72 874 female nurses, aged 38-65 y, without previously diagnosed angina, myocardial infarction (MI), stroke, or cancer at baseline. MAIN OUTCOME MEASURES: Incidence of nonfatal MI, CHD deaths, total CHD events, ischemic, and total strokes. RESULTS: There were 1679 CHD events (1201 nonfatal) and 1009 strokes (567 ischemic). After adjustment for age and lifestyle factors associated with cardiovascular disease risk, the multivariate relative risks (RR) (95% CI) of total CHD from the lowest to the highest quintile category of phylloquinone intake were 1 (reference), 0.80 (0.69-0.94), 0.86 (0.74-1.00), 0.77 (0.66-0.99), and 0.79 (0.68-0.92), P for trend=0.01. Further adjustment for dietary intakes of saturated fat, polyunsaturated fat, trans fatty acids, eicosapentaenoic, and docosahexaenoic acids, cereal fiber, and folate attenuated the association (RR comparing extreme quintiles 0.84 [0.71-1.00], P for trend=0.12). Incidence rates of total or ischemic strokes were not associated with phylloquinone intake. CONCLUSION: The data suggest that high phylloquinone intake may be a marker for low CHD risk. Dietary and lifestyle patterns associated with phylloquinone intakes, rather than intake of the nutrient itself, might account for all or part of the weak association. .

Adult↗
PubMed2004

Correlates of total homocysteine plasma concentration in type 2 diabetes.

BACKGROUND: Although well-defined in the general population, correlates of total homocysteine (tHcy) plasma concentration have not been sufficiently evaluated in diabetes. We investigated factors potentially associated with tHcy concentration in a cohort of type 2 diabetic subjects. MATERIALS AND METHODS: The common methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism, fasting tHcy, vitamin B12 and folate plasma levels were assessed in 312 diabetic subjects, whose clinical, metabolic and lifestyle information was also available. RESULTS: The MTHFR genotype distribution was comparable to the Hardy-Weinberg equilibrium, with an overall TT homozygous frequency of 22%. Fasting tHcy concentration was significantly higher in men than in women (P < 0.001). Multivariate-adjusted tHcy concentration was significantly different across the quartiles of age (P < 0.001), folate (P = 0.01), vitamin B12 (P = 0.03), creatinine concentrations (P = 0.001) and smoking (P = 0.02). Overall, significant trends were noted for creatinine clearance (P for trend = 0.02) and systolic blood pressure (BP) (unadjusted P for trend = 0.01), whereas no differences were noted according to BMI, diastolic BP, presence of hypertension, and diabetes-related variables, such as diabetes duration, fasting glucose and glycated haemoglobin concentrations, current treatment and diabetes long-term complications. Total homocysteine levels significantly correlated with age, systolic BP, vitamin B12, creatinine and creatinine clearance, but only age, creatinine, folate and vitamin B12 levels were independently associated with tHcy concentration in stepwise regression analysis. CONCLUSIONS: Age, creatinine, folate, vitamin B12, and to a minor extent, sex, smoking, TT genotype and systolic BP were significantly associated with Hcy plasma concentration in type 2 diabetes, whereas no significant associations were noted with diabetes-related variables.

Adult↗
PubMed2002

Plasma homocysteine and parental myocardial infarction in young adults in Jerusalem.

BACKGROUND: A causal role for mildly elevated plasma homocysteine (tHcy) in cardiovascular disease remains undetermined. To address the unresolved issue of the antecedent-consequent directionality of the relationship, we assessed the familial association of tHcy with parental myocardial infarction (MI) in young Israeli men and women. We also compared tHcy concentrations in Jerusalem, where rates of coronary heart disease (CHD) are high, with the United States Third National Health and Examination Survey (NHANES III). METHODS AND RESULTS: A total of 8646 17-year-olds and 6952 parents were examined from 1976 to 1979 in Jerusalem. At ages 28 to 32 years, offspring of parents who experienced a documented MI during a 10-year follow-up (n=133 men, 62 women; 72% response) and offspring of CHD-free parents (n=389 men, 208 women; 71% response) were reexamined. tHcy levels were determined by the same laboratory for the NHANES non-Hispanic white population aged 25 to 34 years (n=379) and the Jerusalem population sample (n=858). Men from Jerusalem, but not women, had clearly higher tHcy levels than the sample from the United States (90th percentile, 23 versus 14 micromol/L). This difference was largely attributable to lower plasma vitamin B12 levels in the Israeli population. Male case offspring had higher adjusted tHcy than did controls (1.9 micromol/L, P=0.002). Logistic modeling revealed a graded increase in risk of parental MI across quintiles of offspring tHcy, with an adjusted odds ratio of 2.7 in the 5th quintile (P=0.0026 for trend). CONCLUSIONS: The higher tHcy in young male offspring of parents with CHD suggests that elevated tHcy precedes manifestation of CHD. The elevated population tHcy in men may contribute to the high incidence of CHD in Israel.

Adolescent↗
PubMed2001

Power Shortage: clinical trials testing the "homocysteine hypothesis" against a background of folic acid-fortified cereal grain flour.

Large randomized, controlled trials of total homocysteine-lowering therapy for the potential reduction of cardiovascular disease outcomes are ongoing in the United States and Canada. These trials are the Vitamin Intervention for Stroke Prevention (VISP) trial, the Women's Antioxidant Cardiovascular Disease Study (WACS), and the Heart Outcomes Prevention Evaluation (HOPE-2). However, the dramatic effect of policies mandating fortification of cereal grain flour products with folic acid may reduce the statistical power of these trials. All three trials assume that the active treatment groups will achieve the same mean effects of total homocysteine-lowering therapy as those reported in the absence of folic acid-fortified cereal grain flour. This paper examines this assumption using data from studies of total homocysteine-lowering therapy in U.S. and Canadian patients with cardiovascular disease who were exposed to products made with folic acid-fortified cereal grain flour. These data showed that the VISP trial, HOPE-2, and WACS will probably achieve only approximately 20% to 25% of the projected treatment effects of mean total homocysteine-lowering therapy (1.0 to 1.5 micromol/L vs. 4.0 to 6.0 micromol/L). As a result, all three trials will be substantially underpowered to test the specific hypotheses of total homocysteine-lowering therapy identified a priori. In contrast, renal transplant recipients have a persistent excess prevalence of hyperhomocysteinemia in the era of fortification but remain very responsive to supraphysiologic doses of folic acid-based supplementation (mean reduction in total homocysteine level, 5.0 to 6.0 micromol/L). Therefore, unlike other populations with normal renal function that are at high risk for cardiovascular disease but are profoundly affected by fortification efforts, renal transplant recipients continue to merit serious consideration for a controlled trial of the "homocysteine hypothesis."

Arteriosclerosis↗
PubMed2001

Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels.

BACKGROUND: Lower vitamin B(6) concentrations are reported to confer an increased and independent risk for cardiovascular disease (CVD). The mechanism underlying this relationship, however, remains to be defined. Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B(6) levels. Despite a clear distinction in pathophysiology, inflammatory reaction may be the major link between these diseases. We hypothesized a relationship between pyridoxal 5'-phosphate (PLP), the active form of vitamin B(6), and the marker of inflammation C-reactive protein (CRP). We also evaluated whether total plasma homocysteine (tHcy), a well-defined risk factor for CVD and a major determinant of plasma PLP levels, had a possible role as a mediator of this hypothesized relationship. METHODS AND RESULTS: Data from 891 participants from the population-based Framingham Heart Study cohort were analyzed. Subjects were divided into 2 groups according to normal or elevated CRP values: group 1, CRP <6 mg/L; group 2, CRP >/=6 mg/L. Plasma PLP levels were substantially lower in group 2 than in group 1 (mean values in group 2, 36.5 nmol/L versus 55.8 nmol/L in group 1, P<0.001). In a multiple logistic regression model adjusted for tHcy, the association of PLP with CRP remained highly significant (P=0.003). CONCLUSIONS: Low plasma PLP is associated with higher CRP levels independently of tHcy. This observation may reflect a vitamin B(6) utilization in the presence of an underlying inflammatory process and represent a possible mechanism to explain the decreased vitamin B(6) levels in CVD.

Aged↗
PubMed2001

Long-term nutrient intake and early age-related nuclear lens opacities.

OBJECTIVE: To assess the relation between usual nutrient intake and subsequently diagnosed age-related nuclear lens opacities. SUBJECTS: Four hundred seventy-eight nondiabetic women aged 53 to 73 years from the Boston, Mass, area without previously diagnosed cataracts sampled from the Nurses' Health Study cohort. METHODS: Usual nutrient intake was calculated as the average intake from 5 food frequency questionnaires that were collected during a 13- to 15-year period before the evaluation of lens opacities. The duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined nuclear opacities as a nuclear opalescence grade of 2.5 or higher using the Lens Opacification Classification System III. RESULTS: The prevalence of nuclear opacification was significantly lower in the highest nutrient intake quintile category relative to the lowest quintile category for vitamin C (P<.001), vitamin E (P =.02), riboflavin (P =.005), folate (P =.009), beta-carotene (P =.04), and lutein/zeaxanthin (P =.03). After adjustment for other nutrients, only vitamin C intake remained significantly associated (P =.003 for trend) with the prevalence of nuclear opacities. The prevalence of nuclear opacities was significantly lower (P<.001) in the highest vitamin C intake quintile category relative to the lowest quintile category (odds ratio, 0.31; 95% confidence interval, 0.16-0.58). There were also statistically significant trends of decreasing prevalence of nuclear opacities with increasing duration of use of vitamin C (P =.004 for trend), vitamin E (P =.03 for trend), and multivitamin (P =.04 for trend) supplements, but only duration of vitamin C supplement use remained significantly associated with nuclear opacities after mutual adjustment for use of vitamin E (P =.05 for trend) or multivitamin (P =.02 for trend) supplements. The prevalence of nuclear opacities was significantly lower (P =.004) for women who used a vitamin C supplement for 10 or more years relative to women who never used vitamin C supplements (odds ratio, 0.36; 95% confidence interval, 0.18-0.72). Plasma measures of vitamins C and E taken at the eye examination were also inversely associated with the prevalence of nuclear opacities. CONCLUSION: These results provide additional evidence that antioxidant nutrients play a role in the prevention of age-related nuclear lens opacities.

Aged↗
PubMed2001

Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey.

Hypothyroid (thyroid stimulating hormone (TSH)> or =20 mIU/l; N=32) participants in the third National Health and Nutrition Examination Survey, Phase 2 (1991-1994) were compared with non-hypothyroid subjects (0.5 mIU/l 12 micromol/l) and hypercholesterolemia (serum total cholesterol>6.2 mmol/l). After controlling for age, gender, and race ethnicity, the odds ratios (95% confidence interval (CI)) relating hypothyroidism to hyperhomocysteinemia and high total cholesterol were 4.9 (1.8-14.0) and 8.0 (2.9-21.9), respectively. Based on 26 hypothyroid and 5811 non-hypothyroid subjects with triglyceride concentration < or =2.82 mmol/l, the odds ratio for the relationship between hypothyroidism and high low-density lipoprotein (LDL)-cholesterol (>4.6 mmol/l by the Friedewald equation) was 5.3 (95% CI, 1.3-20.9). Adding additional terms to the multivariate logistic regression model had little effect on the odds ratios relating hypothyroidism to high total or LDL-cholesterol, but adding terms for serum creatinine concentration >123.8 micromol/l and for red blood cell folate and serum vitamin B-12 concentrations resulted in an attenuated, but still significant (P<0.05), odds ratio relating hypothyroidism to hyperhomocysteinemia (2.5; 95% CI, 1.0-6.1). Controlling for cigarette smoking, heart attack/stroke history, body mass index, and serum albumin concentration did not affect the odds ratios. Hyperhomocysteinemia and hypercholesterolemia could help to explain the increased risk for arteriosclerotic coronary artery disease in hypothyroidism.

Adult↗
PubMed2001

The 1298A-->C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine.

A common mutation in methylenetetrahydrofolate reductase (MTHFR), 677C-->T, is associated with reduced enzyme activity, a thermolabile enzyme and mild hyperhomocysteinemia, a risk factor for vascular disease. Recently, a second common mutation (1298A-->C; glutamate to alanine) was reported, but this mutation was suggested to increase homocysteine only in individuals who carried the bp677 variant. To evaluate the functional consequences of this mutation, we performed site-directed mutagenesis and in vitro expression. For in vivo assessment of clinical impact, we examined the 1298A-->C genotypes and plasma homocysteine in 198 individuals from the NHLBI Family Heart Study that had previously been assessed for the 677 substitution. Site-directed mutagenesis of the human cDNA was performed to generate enzymes containing each of the two mutations, as well as an enzyme containing both substitutions. Enzyme activity and thermolability were assessed in bacterial extracts. The activity of the wild-type cDNA was designated as 100%; mutant enzymes containing the 1298 and 677 mutations separately had 68% (+/-5.0) and 45% (+/-10.8), respectively, of control activity while the enzyme containing both mutations had 41% (+/-12.8) of control activity. The 1298 mutation was not associated with a thermolabile enzyme. In the Family Heart Study, fasting homocysteine was significantly higher (P<0.05) in individuals heterozygous for both substitutions, compared to individuals who carried only the 677C-->T variant. This study suggests that two variants in MTHFR should be assessed as genetic risk factors for hyperhomocysteinemia.

Blotting, Western↗
PubMed2001

Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine: critical impact of true glomerular filtration rate.

Conflicting data have been reported concerning the independent association between proteinuria and plasma total homocysteine (tHcy) levels, particularly among chronic renal disease (CRD) patients with a normal range serum creatinine. Studies of this potential relationship have been limited by failure to assess true GFR, failure to assess proteinuria in a quantitative manner, or arbitrary restriction of the range of proteinuria examined. We examined the potential independent relationship between plasma tHcy levels and a wide range of quantitatively determined proteinuria (i.e., 0.000-8.340 g/day), among 109 CRD patients with a normal range serum creatinine (range; 0.8-1.5 mg/dl; median=1.2 mg/dl). Glomerular filtration rate (GFR) was directly assessed by iohexol clearance, and plasma status of folate, pyridoxal 5'-phosphate, and B12, along with serum albumin, were also determined. Linear modeling with ANCOVA revealed that proteinuria was not independently associated with tHcy levels (partial R=0.127; P=0.201), after adjustment for potential confounding by GFR (partial R=0.408; P<0.001), age, sex, plasma B-vitamin status, and serum albumin. Moreover, descending across quartiles (Q) [from Q4 to Q1] of GFR, ANCOVA-adjusted (i.e., for age, sex, and folate status) geometric mean tHcy levels (micromol/l) were significantly increased: tHcy Q4 GFR=9.6; tHcy Q3 GFR=10.5; tHcy Q2 GFR=11.9; tHcy Q4 GFR=14.5; P<0.001 for overall Q difference. We conclude that across a broad spectrum of quantitatively determined proteinuria, after adjustment for true GFR, in particular, there is no independent relationship between proteinuria and tHcy levels among CRD patients with a normal range serum creatinine.

Adult↗
PubMed2001

Rapid communication: L-folinic acid versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients.

BACKGROUND: The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid (FA). We evaluated whether a high-dose L-folinic acid-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients, as suggested by a recent uncontrolled report. METHODS: We block-randomized 48 chronic, stable hemodialysis patients based on their screening predialysis tHcy levels, sex, and dialysis center into two groups of 24 subjects treated for 12 weeks with oral FA at 15 mg/day or an equimolar amount (20 mg/day) of oral L-folinic acid (FNA) [L-5-formyltetrahydrofolate]. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12. RESULTS: The mean percentage (%) reductions (with 95% CIs) in predialysis tHcy were not significantly different [FNA = 22.1% (11.8 to 31.4%), FA = 20.7% (11.7 to 30.5%), P = 0.950 by paired t test]. Final on-treatment values (mean with 95% CI) were as follows: FNA, 15.9 micromol/L (14.0 to 18.0); FA, 16.9 micromol/L (14.8 to 18.8). Moreover, in those subjects with baseline tHcy levels >/=14 micromol/L, neither treatment resulted in "normalization" of tHcy levels (that is, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients [FNA = 2 out of 22 (9.1%); FA = 2 out of 24 (8.3%); Fisher's exact test of between groups difference, P = 1.000]. CONCLUSIONS: Relative to high-dose FA, high-dose oral L-folinic acid-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (that is,> 90%) exhibits mild hyperhomocysteinemia refractory to treatment with either regimen.

Aged↗
PubMed2001

Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients.

BACKGROUND: Hyperhomocysteinemia, a putative atherothrombotic risk factor, is observed in at least 85% of patients undergoing maintenance hemodialysis (HD), as well as 65 to 70% of renal transplant recipients (RTRs). The hyperhomocysteinemia regularly found in HD patients is largely refractory to combined oral vitamin B supplementation featuring supraphysiological doses of folic acid (FA). Relative to their HD counterparts, the hyperhomocysteinemia of RTRs appears to be considerably less refractory to treatment with high-dose FA-based vitamin B supplementation regimens, although controlled comparison data are lacking. We evaluated whether improved total homocysteine (tHcy)-lowering efficacy could be achieved in chronic HD patients with a high-dose L-5-methyltetrahydrofolate (MTHF)-based regimen, as suggested by recent uncontrolled findings, and compared the relative responsiveness of RTRs and HD patients with equivalent baseline tHcy levels, to 12 weeks of tHcy lowering with combined folate-based vitamin B treatment. METHODS: First, we blocked randomized 50 chronic, stable HD patients based on their screening predialysis tHcy levels, sex, and dialysis center into two groups of 25 subjects treated for 12 weeks with oral FA at 15 mg/day, or an equimolar amount (17 mg/day) of oral MTHF. All 50 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12. RESULTS: The mean percentage (%) reductions (+/- 95% confidence intervals) in predialysis tHcy were not significantly different [MTHF 17.0% (12.0 to 22.0%), FA 14.8% (9.6 to 20.1%), P = 0.444 by matched analysis of covariance adjusted for pretreatment tHcy]. Final on-treatment values (mean with 95% confidence interval) were: MTHF, 20.0 micromol/L (18.8 to 21.2); and FA, 19.5 micromol/L (18.3 to 20.7). Moreover, neither treatment resulted in "normalization" of tHcy levels (that is, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients [MTHF, 2 out of 25 (8%); FA, 0 out of 25 (0%); Fisher's exact test of between groups difference, P = 0.490]. Second, we compared the relative responsiveness of (N = 10) RTRs and (N = 39) HD patients with equivalent baseline tHcy levels (RTR range of 14.2 to 23.6 micromol/L, and HD range of 14.4 to 24.9 micromol/L) to 12 weeks of tHcy-lowering treatment. The RTRs received 2.4 mg/day of FA, 50.0 mg/day of vitamin B6, and 0.4 mg/day of vitamin B12, while the HD patients received 15 mg/day of FA or an equimolar amount (17 mg/day) of the reduced folate, MTHF, in addition to 50.0 mg/day of vitamin B6 and 1.0 mg/day of vitamin B12. The mean percentage (%) reductions (+/- 95% confidence interval) in tHcy were as follows: RTR 28.1% (16.2 to 40.0%); HD 12.1% (6.6 to 17.7%, P = 0.027 for comparison of between groups differences by analysis of covariance adjusted for baseline tHcy levels). Moreover, 5 out of 10 (50.0%) of the RTR versus only 2 out of 39 (5.1%) of the HD patients had final on-treatment tHcy levels <12 micromol/L (P = 0.002 for comparison of between groups differences by Fisher's exact test). CONCLUSIONS: First, in comparison to high-dose FA, high-dose oral MTHF-based supplementation does not afford improved tHcy-lowering efficacy among HD patients. The preponderance of HD patients (that is,> 90%) exhibits mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution. Second, relative to RTR with comparable baseline tHcy levels, the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering vitamin B treatment regimens featuring supraphysiological amounts of FA or the reduced folate MTHF. Accordingly, RTRs are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering vitamin B intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease.

Adult↗
PubMed2001

Serum cystatin C is an independent predictor of total homocysteine levels in stable Korean renal transplant recipients with normal serum creatinine.

OBJECTIVES: To examine the determinants of fasting plasma total homocysteine (tHcy) levels such as cystatin C, serum creatinine (SCr), estimated glomerular filtration rate (GFR) from Cockroft-Gault equation, albumin, plasma folate, vitamin B12, and pyridoxal-5'-phosphate (PLP) among Korean renal transplant recipients (RTR) with normal SCr levels (< or =1.4 mg/dL). DESIGN: Cross-sectional study. SETTING: Nephrology and Transplant Service, Catholic University Kangnam St. Mary's Hospital, Seoul, Korea. PARTICIPANTS: Fifty-one chronic stable Korean RTR with normal SCr levels (< or =1.4 mg/dL) 6 months or more following transplantation. MEASURES: Medical record review, anthropometric measurements, and overnight (10 to 14 hours) fasting blood samples for measurement of plasma tHcy, folate, vitamin B12, PLP, SCr, albumin, and cystatin C. RESULTS: General linear regression model including age, gender, vitamin status, and measurements of renal function showed that cystatin C and folate were independent predictors of tHcy levels. The partial regression coefficient for folate was -0.444 (P <.01) and for cystatin C, it was +0.334 (P <.05). SCr, estimated GFR, vitamin B12, PLP, age, and gender were not independent predictors of tHcy levels in this model. CONCLUSION: Both cystatin C and folate status were major independent determinants of fasting tHcy levels in the subgroup of Korean RTR with normal SCr.

Adult↗
PubMed2001

Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.

BACKGROUND: Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. OBJECTIVE: Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. DESIGN: We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. RESULTS: Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). CONCLUSIONS: Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations.

Adult↗
PubMed2001

Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores.

BACKGROUND: Although iron deficiency occurs commonly in vulnerable groups of women of reproductive age, infants, and children, less is known about the iron nutriture of the elderly. OBJECTIVE: Our objective was to evaluate the iron status of a noninstitutionalized, elderly US population, with a particular focus on 2 concerns unique to the elderly: 1) potential confounding effects of chronic disease on iron measures and 2) increased occurrence of elevated iron stores. DESIGN: Multiple iron measures, including serum ferritin (SF), transferrin saturation, mean cell volume, and hemoglobin, were used to evaluate the prevalence of iron deficiency (ID), iron deficiency anemia (IDA), and other measures of iron nutriture in 1016 elderly white Americans aged 67-96 y from the Framingham Heart Study. "Diseased" subjects were defined as those with possible pathologically altered iron measures due to inflammation, infection, elevated liver enzymes, hereditary hemochromatosis, or cancer. The effect of altered iron status on various prevalence estimates was assessed. RESULTS: The elderly subjects had a low prevalence of ID (2.7%), IDA (1.2%), and depleted iron stores (3%; SF < 12 microg/L). In contrast, 12.9% had elevated iron stores (SF > 300 microg/L in men and SF > 200 microg/L in women), of which only 1% was attributable to chronic disease. The prevalence of ID, IDA, and depleted iron stores was unaffected by the presence of chronic disease. CONCLUSIONS: The Framingham Heart Study cohort is an iron-replete elderly population with a high prevalence of elevated iron stores in contrast with a low prevalence of iron deficiency, with insignificant effects of chronic disease on these iron status estimates. The likely liability in iron nutriture in free-living, elderly white Americans eating a Western diet is high iron stores, not iron deficiency.

Aged↗
PubMed2001

Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey.

BACKGROUND: High circulating total homocysteine (tHcy) concentrations are associated with stroke, which is a major cause of cognitive dysfunction. Blood homocysteine concentrations are inversely correlated with performance on some cognitive-function tests and a relation was recently shown between hyperhomocysteinemia and Alzheimer disease. OBJECTIVE: The objective was to evaluate the relation between serum tHcy concentrations and performance on short delayed-recall tests of elderly men and women participating in the third National Health and Nutrition Examination Survey, phase 2 (1991--1994). DESIGN: Subjects were aged > or =60 y. Subjects reported no previous stroke, completed > or =8 y of education, and took a test of delayed recall of story ideas (n = 1200) or words (n = 1270). RESULTS: After adjustment for sex, age, race-ethnicity, income, years of education, and serum creatinine concentration, subjects in the upper half of the folate distribution recalled, on average, >4 of 6 story ideas; subjects with lower folate status recalled significantly fewer ideas (P < 0.001). Of the subjects with low folate status, story recall was significantly poorer in those with serum tHcy concentrations above the 80th percentile of the distribution (13.7 micromol/L) than in those with lower tHcy concentrations (P < 0.03). The odds ratio relating hyperhomocysteinemia to recall of > or =1 of 3 previously learned words was 0.3 (95% CI: 0.2, 0.7) after adjustment for the 5 demographic factors alone and was 0.4 (0.2, 0.9) after further adjustment for serum folate concentration. CONCLUSION: Hyperhomocysteinemia is related to poor recall and this association was partially independent of folate status.

Age Factors↗
PubMed2001

Aspirin intake and the use of serum ferritin as a measure of iron status.

BACKGROUND: Atherosclerosis, a primary cause of myocardial infarction (MI), is an inflammatory disease. Aspirin use lowers risk of MI, probably through antithrombotic and antiinflammatory effects. Because serum ferritin (SF) can be elevated spuriously by inflammation, reported associations between elevated SF, used as an indicator of iron stores, and heart disease could be confounded by occult inflammation and aspirin use if they affect SF independently of iron status. OBJECTIVE: We tested the hypothesis that aspirin use is associated with reduced SF. DESIGN: We used analysis of covariance to investigate the relation between SF and categories of aspirin use in 913 elderly participants aged 67-96 y in the Framingham Heart Study. RESULTS: After adjustment for sex, age, body mass index, smoking, alcohol use, concentrations of C-reactive protein and liver enzymes, white blood cell count, and use of nonaspirin nonsteroidal antiinflammatory drugs and other medications, subjects who took >7 aspirins/wk had a significantly lower (by 25%) geometric mean SF than did nonusers, who took <1 aspirin/wk (71 compared with 95 microg/L, respectively; P for trend = 0.004). This effect of aspirin on SF was more marked in diseased subjects than in healthy subjects (mean SF was 50% lower compared with 21% lower, respectively). CONCLUSIONS: Aspirin use is associated with lower SF. We suggest this effect results from possible increased occult blood loss and a cytokine-mediated effect on SF in subjects with inflammation, infection, or liver disease. The relations between aspirin, inflammation, and SF may confound epidemiologic associations between elevated SF, as an indicator of iron stores, and heart disease risk.

Aged↗
PubMed2001

Folic acid fortification increases red blood cell folate concentrations in the Framingham study.

In 1996 the Food and Drug Administration (FDA) issued a regulation to take effect in January 1998 that all enriched cereal grain products include 140 microg of folic acid/100 g. The present cross-sectional study was undertaken to assess the effect of this fortification on RBC folate concentrations in the Framingham Offspring Cohort. Among those who did not take B-vitamin supplements, we compared RBC folate in 561 individuals who were examined before implementation of the FDA mandatory folic acid fortification (not exposed) vs. 354 individuals who were examined after implementation of fortification (exposed). We calculated the prevalence of deficient (<160 microg/L, 362.6 nmol/L) and acceptable (>200 microg/L, 453.2 nmol/L) RBC folate concentrations in both groups. Those exposed to folic acid fortification had a mean RBC folate of 450.0 microg/L (1019.7 nmol/L), a value 38% higher than the mean RBC folate of 325.3 microg/L (737.1 nmol/L) in those who were not exposed to fortification (P < 0.001). The prevalence of individuals with deficient RBC folate was 4.9% in the group not exposed to fortification compared with 1.9% in the group exposed to fortification (P < 0.02), and the prevalence of individuals with acceptable RBC folate was 87.0% in the group not exposed to fortification compared with 96.1% in the group exposed to fortification (P < 0.001). Similar results were seen in individuals who used supplements containing B-vitamins. The results of this study showed that in this cohort, the introduction of folic acid fortification significantly improved folate nutritional status measured as RBC folate.

Adult↗