Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study

Bots, Michiel L.; Launer, Lenore J.; Lindemans, Jan; Hofman, Albert; Grobbee, D.E.

doi:10.1046/j.1365-2796.1997.00239.x

Cited by 103 publications

(57 citation statements)

References 25 publications

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“…32 Weak associations, but usually only in certain subpopulations, were found in vascular disease patients and in population-based studies. [15][16][17][33][34][35][36] In our study, we found a borderline statistically significant effect of log tHcy levels on CIMT, so they are still in line with a small effect.…”

Section: Discussionsupporting

confidence: 64%

“…[12][13][14] Atherosclerosis may be another pathway by which tHcy is linked with arterial disease. In general, the evidence of a relationship between tHcy levels and CIMT as a measure of generalized atherosclerosis varies, with some studies reporting this association [15][16][17][18] while others do not. 12,14,[19][20][21] To gain more insight into the association of circulating tHcy with PWV and CIMT, we studied their associations in a population-based sample of 376 men.…”

Section: Introductionmentioning

confidence: 99%

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Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

et al. 2007

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Elevated plasma homocysteine (tHcy) is considered as a risk factor for cardiovascular events, and has been associated with arterial stiffness and subclinical atherosclerosis in subjects with classical cardiovascular risk factors. The aim of this study is to investigate the association of plasma tHcy with functional and structural changes in the large arteries by measuring aortic pulsewave velocity (PWV) and carotid artery intima-media thickness (CIMT). In a population-based sample of 376 middle-aged and elderly men, tHcy levels were measured by using fluorescence polarization immunoassay. Aortic stiffness was assessed non-invasively by measuring carotid-femoral PWV with the use of applanation tonometry. CIMT was measured by ultrasonography. We used multivariate linear regression analysis with the logtransformed value of tHcy as the determinant, and aortic PWV and CIMT as outcomes. In the univariate model, PWV increased with increasing tHcy concentration; PWV increased by 2.64 m/s (95% confidence interval (CI) 1.74; 3.54) per unit change in log tHcy. After adjustment for confounders, no statistically significant association remained; PWV increased by 0.42 m/s (95% CI À0.27; 1.11) per unit change in log tHcy. Furthermore, in the univariate model, CIMT increased significantly with increasing tHcy concentration; CIMT increased by 0.19 mm (95% CI 0.11; 0.26) per unit increase log tHcy. This association was attenuated and did not remain significant after additional adjustment for age and cardiovascular confounders (b ¼ 0.06 (95% CI À0.01; 0.13)). The results of this study do not support the presence of an independent relationship between circulating tHcy levels and large artery stiffness and thickness.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

et al. 2007

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“…20,21 More recently, in the Rotterdam cohort, a positive association between homocysteine and stroke has also been reported. 22 In this study, however, the relation was non-linear with a two-fold increase in risk in the upper quintile relative to rest of the distribution. Additional support for the homocysteine stroke hypothesis is provided by cross-sectional studies, showing independent associations between homocysteine concentrations and carotid atherosclerosis.…”

Section: Recent Prospective Studiescontrasting

confidence: 67%

“…13 There are additional concerns regarding unmeasured and residual confounding due to dietary and other lifestyle factors associated with hyperhomocysteinaemia. 14,15 The findings from the small number of prospective studies that have addressed associations between tHcy concentrations and incident coronary heart diseases (CHD) or stroke are inconsistent [16][17][18][19][20][21][22] Homozygosity for a defective thermolabile variant of MTHFR, a common genetic polymorphism which results in hyperhomocysteinemia, has not been consistently linked with cardiovascular disease endpoints. 23,24 Although the importance of gene markers will vary depending on relevant environmental exposures, diet in this instance, the findings from gene association studies conducted to-date are distinctly unimpressive.…”

Section: Thcy and Cardiovascular Diseasementioning

confidence: 99%

Homocysteine, hypertension and stroke

Perry

1999

J Hum Hypertens

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The balance of evidence from observational studies suggests that elevated homocysteine levels are associated with increased risk of carotid artery disease and stroke. There is however a paucity of prospective studies. There are also concerns regarding confounding due to factors associated with hyperhomocysteinemia, including renal impairment, an atherogenic diet and cigarette smoking. Homozygosity for a defective thermolabile variant of MTHFR, a common genetic polymorphism which results in hyperhomocysteinemia, has not been consistently linked with stroke or other vascular disease. There is a need for additional prospective studies with data on relevant confounders, sufficient power to characterise the form of the association between homocysteine concentrations and stroke risk, whether linear or threshold, and power to study interactions between homocysteine, other dietary markers and established stroke risk factors such as smoking and

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“…Folate intake is associated with homocysteine levels, a well-known risk factor for vascular disease [30][31][32][33][34][35]. It is possible that homocysteine levels contribute to vascular disease through a direct effect on vascular endothelial cells [36].…”

Section: Discussionmentioning

confidence: 99%

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

Corrada

Kawas

Hallfrisch

et al. 2005

Alzheimer's & Dementia

137

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Background-Study findings have suggested an association between Alzheimer's disease (AD) risk and several vitamins and have speculated about their use as preventive agents. Here, we examine whether total intake (intake from diet plus supplements) of antioxidant vitamins (E, C, carotenoids) and B vitamins (folate, B 6 , and B 12 ) is associated with a reduced risk of AD.Methods-Participants were 579 nondemented elderly volunteers from the Baltimore Longitudinal Study of Aging who completed dietary diaries and recorded supplement intake for a 7-day period. Cox regression was used to estimate the relative risk (RR) of AD associated with total vitamin intake categorized into levels above or below the Recommended Dietary Allowance (RDA).Results-After a mean follow-up of 9.3 years, AD developed in 57 participants. Higher intake of folate (RR, 0.41; 95% confidence interval [CI], 0.22 to 0.76), vitamin E (RR, 0.56; 95% CI, 0.30 to 1.06), and vitamin B 6 (RR, 0.41; 95% CI, 0.20 to 0.84) were associated individually with a decreased risk of AD after adjusting for age, gender, education, and caloric intake. When these 3 vitamins were analyzed together, only total intake of folate at or above the RDA (RR, 0.45; 95% CI, 0.21 to 0.97) was associated with a significant decreased risk of AD. No association was found between total intake of vitamins C, carotenoids, or vitamin B 12 and risk of AD.Conclusions-These findings suggest that total intake of folate at or above the RDA is associated with a reduced risk of AD. Additional studies are necessary to further investigate whether folate or other(s) unmeasured factor(s) may be responsible for this reduction in risk.

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Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study

Abstract: In subjects aged 55-74 years elevated tHcy is associated with an increased risk of atherosclerosis and cardiovascular disease. The lack of association in those aged > or = 75 years most probably reflect selective mortality.

Cited by 103 publications

References 25 publications

Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men

Homocysteine, hypertension and stroke

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

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