A study of the average effect of the 3'APOB-VNTR polymorphism on lipidemic parameters could explain why the short alleles (<35 repeats) are rare in centenarians

BACKGROUND: In studies on the genetics of human aging, we observed an age-related variation of the 3'APOB-VNTR genotypic pool (alleles: Short, S, <35 repeats; Medium, M, 35–39 repeats; Long, L, >39 repeats) with the homozygous SS genotype showing a convex frequency trajectory in a healthy aging population. This genotype was rare in centenarians, thus indicating that the S alleles are unfavorable to longevity, while common in adults, thus indicating a protective role at middle age. This apparent paradox could be due to possible effects exerted by the above polymorphism on lipidemic parameters. Aim of the work was to get insights into these puzzling findings METHODS: We followed a double strategy. Firstly, we analyzed the average effects of S (α(S)), M (α(M)), and L (α(L)) alleles on lipidemic parameters in a sample of healthy people (409 subjects aged 20–102 years) recruited in Calabria (southern Italy). The (α(S)), (α(M)), and (α(L)) values were estimated by relating 3'APOB-VNTR genotypes to lipidemic parameters, after adjustment for age, sex and body mass index (multiple regression). Then, we analyzed the S alleles as susceptibility factors of Cardiovascular Atherosclerotic Disease (CD) in CD patients characterized either by low serum HDL-Cholesterol or by high serum LDL-Cholesterol (CD-H and CD-L patients, 40 and 40 subjects respectively). The Odds Ratios (OR) were computed for carriers of S alleles in CD-H and CD-L patients matched for origin, sex and age with controls extracted from the sample of healthy subjects. RESULTS: By the analysis of the healthy sample group we found that the S alleles lower the average values of serum Total Cholesterol (α(S )= -5.98 mg/dL with [-11.62 ÷ -0.74] 95% confidence interval) and LDL-Cholesterol (α(S )= -4.41 mg/dL with [-8.93 ÷ -0.20] 95% confidence interval) while the alleles M and L have no significant effect on the lipidemic phenotype. In line with these findings, the analysis of CD patients showed that the S alleles are protective as for CD-L (O.R. = 0.55 with [0.21 ÷ 0.98] 95% confidence interval) while neutral as for CD-H (O.R. = 0.75 with [0.32 ÷ 1.60] 95% confidence interval). CONCLUSION: On the whole, the S alleles would be advantageous in adults (by protecting from CD-L) while dangerous in the elderly, probably by lowering serum cholesterol below a critical threshold. This could explain the convex frequency trajectory of SS genotypes previously observed in a healthy aging population

Phenomenon of declining blood pressure in elderly - high systolic levels are undervalued with Korotkoff method

<p>Abstract</p> <p>Background</p> <p>Systolic blood pressure (SBP) decline has been reported in octogenarians. The aim was to study if it could be observed while measuring SBP with two methods: Korotkoff (K-BP) and Strain-Gauge-Finger-Pletysmography (SG-BP), and which of them were more reliable in expressing vascular burden.</p> <p>Methods</p> <p>A cohort of 703 men from a population of Malmö, Sweden, were included in "Men born in 1914-study" and followed-up at ages: 68 and 81 years. 176 survivors were examined with K-BP and SG-BP at both ages, and 104 of them with Ambulatory Blood Pressure at age 81/82. Ankle Brachial Index (ABI) was measured on both occasions, and Carotid Ultrasound at age 81.</p> <p>Results</p> <p>From age 68 to 81, mean K-BP decreased in the cohort with mean 8.3 mmHg, while SG-BP increased with 13.4 mmHg. K-BP decreased in 55% and SG-BP in 31% of the subjects. At age 81, K-BP was lower than SG-BP in 72% of subjects, and correlated to high K-BP at age 68 (r = --.22; p < .05). SG-BP at age 81 was correlated with mean ambulatory 24-h SBP (r = .480; p < .0001), daytime SBP (r = .416; p < .0001), nighttime SBP (r = .395; p < .0001), and daytime and nighttime Pulse Pressure (r = .452; p < .0001 and r = .386; p < .0001). KB-BP correlated moderately only with nighttime SBP (r = .198; p = .044), and daytime and nightime pulse pressure (r = .225; p = .021 and r = .264; p = .007). Increasing SG-BP from age 68 to 81, but not K-BP, correlated with: 24-h, daytime and nighttime SBP, and mean daytime and nighttime Pulse Pressure. Increasing SG-BP was also predicted by high B-glucose and low ABI at age 68, and correlated with carotid stenosis and low ABI age 81, and the grade of ABI decrease over 13 years.</p> <p>Conclusion</p> <p>In contrast to K-BP, values of SG-BP in octogenarians strongly correlated with Ambulatory Blood Pressure. The SG-BP decline in the last decade was rare, and increasing SG-BP better than K-BP reflected advanced atherosclerosis. It should be aware, that K-BP underdetected 46% of subjects with SG-BP equal/higher than 140 mmHg at age 81, which may lead to biased associations with risk factors due to differential misclassification by age.</p

Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.</p> <p>Methods</p> <p>We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.</p> <p>Results</p> <p>We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects ≥65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700000 subjects taking simvastatin and over 50000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44–0.48, <it>p </it>< 0.0001) and 0.91 (CI 0.80–1.02, <it>p </it>= 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4–0.55, <it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.</p

Cognitive health among older adults in the United States and in England

<p>Abstract</p> <p>Background</p> <p>Cognitive function is a key determinant of independence and quality of life among older adults. Compared to adults in England, US adults have a greater prevalence of cardiovascular risk factors and disease that may lead to poorer cognitive function. We compared cognitive performance of older adults in the US and England, and sought to identify sociodemographic and medical factors associated with differences in cognitive function between the two countries.</p> <p>Methods</p> <p>Data were from the 2002 waves of the US Health and Retirement Study (HRS) (n = 8,299) and the English Longitudinal Study of Ageing (ELSA) (n = 5,276), nationally representative population-based studies designed to facilitate direct comparisons of health, wealth, and well-being. There were differences in the administration of the HRS and ELSA surveys, including use of both telephone and in-person administration of the HRS compared to only in-person administration of the ELSA, and a significantly higher response rate for the HRS (87% for the HRS vs. 67% for the ELSA). In each country, we assessed cognitive performance in non-hispanic whites aged 65 and over using the same tests of memory and orientation (0 to 24 point scale).</p> <p>Results</p> <p>US adults scored significantly better than English adults on the 24-point cognitive scale (unadjusted mean: 12.8 vs. 11.4, P < .001; age- and sex-adjusted: 13.2 vs. 11.7, P < .001). The US cognitive advantage was apparent even though US adults had a significantly higher prevalence of cardiovascular risk factors and disease. In a series of OLS regression analyses that controlled for a range of sociodemographic and medical factors, higher levels of education and wealth, and lower levels of depressive symptoms, accounted for some of the US cognitive advantage. US adults were also more likely to be taking medications for hypertension, and hypertension treatment was associated with significantly better cognitive function in the US, but not in England (P = .014 for treatment × country interaction).</p> <p>Conclusion</p> <p>Despite methodological differences in the administration of the surveys in the two countries, US adults aged ≥ 65 appeared to be cognitively healthier than English adults, even though they had a higher burden of cardiovascular risk factors and disease. Given the growing number of older adults worldwide, future cross-national studies aimed at identifying the medical and social factors that might prevent or delay cognitive decline in older adults would make important and valuable contributions to public health.</p