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Associations of C-reactive protein (CRP) and fibrinogen with death may weaken over time. Combining both markers may improve prediction of death in older adults. In 5,828 Cardiovascular Health Study participants (United States, 1989–2000), 383 deaths (183 cardiovascular disease (CVD)) in years 1–3 (early) and 914 deaths (396 CVD) in years 4–8 (late) occurred. For men, when comparing highest to lowest quartiles, hazard ratios for early death were 4.1 (95% confidence interval (CI): 2.7, 6.3) for CRP and 4.1 (95% CI: 2.7, 6.4) for fibrinogen in models adjusted for CVD risk. For early CVD death, hazard ratios were 4.3 (95% CI: 2.2, 8.4) and 3.4 (95% CI: 1.8, 6.3), respectively. When comparing men in the highest quartiles of both biomarkers with those in the lowest, hazard ratios were 9.6 (95% CI: 4.3, 21.1) for early death and 13.5 (95% CI: 3.2, 56.5) for early CVD death. Associations were weaker for late deaths. For women, CRP (hazard ratio = 2.3, 95% CI: 1.4, 3.9), but not fibrinogen (hazard ratio = 1.3, 95% CI: 0.8, 2.2), was associated with early death. Results were similar for CVD death. Neither was associated with late deaths. CRP and fibrinogen were more strongly associated with death in older men than women and more strongly associated with early than late death. Combining both markers may identify older men at greatest risk of near-term death. [ABSTRACT FROM AUTHOR]

Recent developments in genetic sequencing technology now make it possible to genotype large numbers of single nucleotide polymorphisms (SNPs) in large samples. Many association studies using SNP data are now being carried out. Typically, these observational studies establish whether certain haplotypes or individual SNPs are associated with a health outcome. Few methods exist for finding interaction effects among multiple SNPs or between SNPs and environmental factors. In this paper, the authors describe logic regression, an exploratory method with which to identify interactions for further research. They illustrate this method using data from a US case-control study of myocardial infarction and stroke (1995–1999) carried out among 1,614 persons in Washington State who were genotyped for 32 SNPs on five genes in the renin-angiotensin system. [ABSTRACT FROM AUTHOR]

The telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD). Leukocyte telomere length, as expressed by mean terminal restriction fragment (TRF) length, was measured in 419 randomly selected participants from the Cardiovascular Health Study, comprising a community-dwelling cohort recruited in four US communities. The authors investigated associations between TRF length and selected measures of subclinical CVD/risk factors for CVD (data were collected at the 1992/1993 clinic visit) and incident CVD (ascertained through June 2002). In these participants (average age = 74.2 years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs (standard deviation, 0.62). Significant or borderline inverse associations were found between TRF length and diabetes, glucose, insulin, diastolic blood pressure, carotid intima-media thickness, and interleukin-6. Associations with body size and C-reactive protein were modified by gender and age, occurring only in men and in participants aged 73 years or younger. In younger (but not older) participants, each shortened kilobase pair of TRF corresponded with a threefold increased risk of myocardial infarction (hazard ratio = 3.08, 95% confidence interval: 1.22, 7.73) and stroke (hazard ratio = 3.22, 95% confidence interval: 1.29, 8.02). These results support the hypotheses that telomere attrition may be related to diseases of aging through mechanisms involving oxidative stress, inflammation, and progression to CVD. [ABSTRACT FROM AUTHOR]

Background Functional status limitations may be associated with both an increased risk of death and a decreased likelihood of influenza vaccination, and so may confound the association of influenza vaccination and risk of all cause mortality in seniors.Methods We conducted a nested case–control study of persons ≥65 years of age that included 252 cases who died during an influenza season and 576 age-matched controls. We identified functional limitations by medical record review, and compared the effect of adjustment for those factors with that of adjustment for disease covariates defined by diagnosis codes, using methods reported by previous influenza vaccine effectiveness studies, on the association of influenza vaccination and risk of death.Results Functional limitations, such as requiring assistance for bathing, were highly prevalent in cases, even in the subgroup defined as free of comorbidity by diagnosis code criteria, and were associated with a decreased likelihood of vaccination among controls. Adjustment for functional limitations resulted in an estimate of the relative risk of death in vaccinated persons compared with unvaccinated persons that was closer to the null [odds ratio (OR), 0.71; 95% confidence interval (95% CI), 0.47–1.06] than the unadjusted estimate (OR, 0.59; 95% CI, 0.41–0.83). In contrast, adjustment for diagnosis code covariates moved the estimate further from the null (OR, 0.45; 95% CI, 0.30–0.68).Conclusions Functional limitations appear to be important confounders of the association of vaccination and risk of death, while adjustment for diagnosis code covariates did not control for a healthy vaccinee bias. Further research is needed on methods to reduce the influence of bias in observational studies of influenza vaccine effectiveness. [ABSTRACT FROM AUTHOR]

The products of the renin-angiotensin system (RAS) play an important role in the pathogenesis of cardiovascular disease. Studies examining RAS gene variants and cardiovascular disease have focused on single-nucleotide polymorphisms (SNPs) rather than haplotypes, which better characterize the patterns of genetic variation. The authors conducted a population-based, case-control study at Group Health (Seattle, Washington) between 1995 and 1999 to determine whether common haplotypes in the angiotensinogen gene (AGT), the renin gene, the angiotensin-converting enzyme gene, and the angiotensin II receptor type 1 and receptor type 2 genes were associated with the risk of myocardial infarction and stroke among pharmacologically treated hypertensive patients. SNP discovery was done using 23 European-origin samples. Thirty tagSNPs (the minimum sets of SNPs that capture most of the haplotype diversity within a block) were genotyped in cases and controls. Haplotypes were inferred using the program PHASE (http://www.stat.washington.edu/stephens/software.html). The authors used weighted logistic regression to estimate associations and conducted a permutation test to estimate the probability of a chance finding. AGT haplotype B was associated with the risk of myocardial infarction (odds ratio = 1.58, 95% confidence interval: 1.06, 2.35); however, results were not statistically significant given the number of tests performed (permutation p = 0.17). In this case-control study, RAS gene haplotypes were not significantly associated with increased risks of myocardial infarction or stroke. [ABSTRACT FROM AUTHOR]