Are varicose veins a marker for susceptibility to coronary heart disease in men? Results from the Normative Aging Study.
ABSTRACT Clinical observations suggest that varicose veins (VV) are less frequent in patients undergoing infrainguinal bypass surgery for femoral artery occlusive disease. While some previous studies support this relationship, others report that VV are more prevalent in coronary heart disease patients (CHD). This study used the Normative Aging Study (NAS) population to examine the association between VV and symptomatic CHD. The incidence of CHD over 35 years of follow-up was determined in the 2280 initially healthy male volunteers enrolled in the NAS. The incidence of CHD in the VV population and the subjects without VV were compared using Kaplan-Meier survival curves and the log-rank test. A time-dependent proportional hazards regression method was used to further explore the relationship between VV disease and subsequent development of CHD after adjusting for other cardiovascular risk factors. A total of 569 subjects (24.9%) were diagnosed with VV prior to the development of symptomatic CHD, and 1708 (75.1%) were not. Over 35 years of follow-up, 98 subjects with VV developed symptomatic CHD (17.2%), while 363 of those without VV subsequently developed symptomatic CHD (21.2%). Kaplan-Meier survival curves suggested a reduced risk of symptomatic CHD for subjects with VV (p = 0.0001). Further exploration of this relationship in a proportional hazards multivariate model showed VV to be associated with a 36% decreased risk of symptomatic CHD after adjusting for other recognized cardiovascular risk factors. In the NAS population, men with VV were less likely to develop symptomatic CHD over the 35+ years of follow-up than were subjects without VV.
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ABSTRACT: Genes functioning in folate-mediated 1-carbon metabolism are hypothesized to play a role in cardiovascular disease (CVD) risk beyond the current narrow focus on the MTHFR 677 C→T (rs1801133) polymorphism. Using a cohort study design, we investigated whether sequence variants in the network of folate-related genes, particularly in genes encoding proteins related to SHMT1, predict CVD risk in 1131 men from the Normative Aging Study. A total of 330 single nucleotide polymorphisms (SNPs) in 52 genes, selected for function and gene coverage, were assayed on the Illumina GoldenGate platform. Age- and smoking-adjusted genotype-phenotype associations were estimated in regression models. Using a nominal P ≤ 5.00 × 10(-3) significance threshold, 8 SNPs were associated with CVD risk in single locus analyses. Using a false discovery rate (FDR) threshold (P-adjusted ≤1.00 × 10(-1)), a SNP in the GGH gene remained associated with reduced CVD risk, with a stronger association in early onset CVD cases (<55 y). A gene × folate interaction (MAT2B) and 2 gene × vitamin B-12 interactions (BHMT, SLC25A32) reached the FDR P-adjusted ≤2.00 × 10(-1) threshold. Three biological hypotheses related to SHMT1 were explored and significant gene × gene interactions were identified for TYMS by UBE2N, FTH1 by CELF1, and TYMS by MTHFR. Variations in genes other than MTHFR and those directly involved in homocysteine metabolism are associated with CVD risk in non-Hispanic white males. This work supports a role for SHMT1-related genes and nuclear folate metabolism, including the thymidylate biosynthesis pathway, in mediating CVD risk.Journal of Nutrition 05/2012; 142(7):1272-9. DOI:10.3945/jn.111.157180 · 4.23 Impact Factor
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ABSTRACT: V aricose veins and haemorrhoids both involve the venous circulatory system, but it is unclear whether they are predictors of elevated rates of other circulatory diseases. Our aim was to determine whether they are. We analysed an epidemiological database of hospital admission and day-case statistics, constructing cohorts of people admitted for care for varicose veins or haemorrhoids, and comparing their experience of subsequent circulatory diseases with a control cohort. Compared with the control cohort, there was an elevated risk of deep vein thrombosis (DVT) in the varicose veins cohort (rate ratio 1.20; 95% confidence interval 1.08–1.33) but not in the haemorrhoids cohort (0.90; 0.78–1.03). No other circulatory diseases showed significantly elevated risks associated with varicose veins or haemorrhoids. The rate ratio for coronary heart disease in the varicose veins cohort was 0.91 (95% confidence interval 0.88– 0.95) and that in the haemorrhoids cohort was 0.98 (0.94–1.03). We conclude that neither varicose veins nor haemorrhoids showed strong association, either positive or negative, with other circulatory diseases. There was a significant, but numerically modest, elevated risk of DVT associated with varicose veins. The risk of coronary heart disease in people with varicose veins was, if anything, a bit low.