Citations

Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.

We hypothesized that demographic/anthropometric parameters can be used to estimate effective reflecting distance (EfRD), required to derive aortic pulse wave velocity (APWV), a prognostic marker of cardiovascular risk, from peripheral waveforms and that such estimates can discriminate differences in APWV and EfRD with aging and habitual endurance exercise in healthy adults. Ascending aortic pressure waveforms were derived from peripheral waveforms (brachial artery pressure, n = 25; and finger volume pulse, n = 15) via a transfer function and then used to determine the time delay between forward- and backward-traveling waves (Δ tf-b). True EfRDs were computed as directly measured carotid-femoral pulse wave velocity (CFPWV) × ½Δ tf-b and then used in regression analysis to establish an equation for EfRD based on demographic/anthropometric data (EfRD = 0.173·age + 0.661·BMI + 34.548 cm, where BMI is body mass index). We found good agreement between true and estimated APWV (Pearson's R2 = 0.43; intraclass correlation = 0.64; both P < 0.05) and EfRD ( R2 = 0.24; intraclass correlation = 0.40; both P < 0.05). In young sedentary (22 ± 2 years, n = 6), older sedentary (62 ± 1 years, n = 24), and older endurance-trained (61 ± 2 years, n = 14) subjects, EfRD (from demographic/anthropometric parameters), APWV, and ½Δ tf-b (from brachial artery pressure waveforms) were 52.0 ± 0.5, 61.8 ± 0.4, and 60.6 ± 0.5 cm; 6.4 ± 0.3, 9.6 ± 0.2, and 8.1 ± 0.2 m/s; and 82 ± 3, 65 ± 1 and 76 ± 2 ms (all P < 0.05), respectively. Our results demonstrate that APWV derived from peripheral waveforms using age and BMI to estimate EfRD correlates with CFPWV in healthy adults. This method can reliably detect the distal shift of the reflecting site with age and the increase in APWV with sedentary aging that is attenuated with habitual endurance exercise.

Recently, several high-impact reviews suggest that regular aerobic exercise is beneficial for maintaining cognitive function in aging adults. Higher cerebral blood flow and/or cerebrovascular reactivity may explain the favorable effect of exercise on cognition. In addition, prostaglandin-mediated vasodilator responses may be influenced by regular exercise. Therefore, our purpose was to evaluate middle cerebral artery (MCA) vasodilator responses in healthy adults before and after cyclooxygenase inhibition. A total of 16 young (26 ± 6 yr; 8 males, 8 females) and 13 older (64 ± 6 yr; 7 males, 6 females) healthy adults participated in the study. Aerobic fitness was determined by maximal aerobic capacity (V̇o2max) on a cycle ergometer. MCA velocity (MCAv) was measured at baseline and during stepped hypercapnia (2%, 4%, and 6% FiCO2) before and after cyclooxygenase inhibition using indomethacin. To account for differences in blood pressure, cerebrovascular conductance index (CVCi) was calculated as MCAv/mean arterial pressure. Cerebrovascular reactivity slopes were calculated from the correlation between either MCAv or CVCi and end-tidal CO2. Young adults demonstrated greater MCAv reactivity (1.61 ± 0.17 vs. 1.06 ± 0.15 cm·s−1·mmHg−1; P < 0.05) and CVCi reactivity (0.015 ± 0.002 vs. 0.007 ± 0.002 cm·s−1·mmHg−1; P < 0.05) compared with the older adults. There was no association between cerebrovascular reactivity and V̇o2maxin the combined group of subjects; however, in older adults MCAv reactivity was correlated with maximal aerobic fitness ( r = 0.64; P < 0.05). Furthermore, the change in MCAv reactivity (between baseline and indomethacin trials) was also associated with V̇o2max( r = 0.59; P < 0.05) in older adults. Cerebral vasodilator responses to hypercapnia were associated with maximal aerobic capacity in healthy older adults. These results may explain the physiological link between regular aerobic exercise and improved cognitive function in aging adults.

Background —The impact of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) on long-term mortality rates in the presence of various demographic, clinical, and angiographic factors is uncertain in the population of patients suitable for both procedures. Methods and Results —In the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial and registry, 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992. Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality, with particular attention to factors that interact with treatment. Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG (relative risk [RR] 1.78 and 2.63, respectively, P <0.001), and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA (RR 4.08, P <0.001). Factors most strongly associated with high overall mortality rates were insulin-treated diabetes, congestive heart failure, kidney failure, and older age. Black race was also associated with higher mortality rates (RR 1.49, P =0.019). Conclusions —A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization.

BACKGROUND Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart. METHODS AND RESULTS We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF. CONCLUSIONS These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.