Showing papers by "Philimon Gona published in 2008"
TL;DR: In middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD in multivariable models, supporting the concept that dynamic BP provides incremental information to BP at rest and suggesting that exercise diastsolic BP may be a better predictor than exercise systolic BP in this age group.
Abstract: Exaggerated systolic blood pressure (BP) augmentation with exercise has been associated with impaired endothelial function and cardiovascular risk. However, previous studies were largely restricted to men, did not evaluate diastolic BP, and focused on peak exercise measures, which are influenced by effort and fitness level. The aim of this study was to determine the association of exercise BP responses with risk of incident cardiovascular disease (CVD). BP was assessed during stage 2 of the Bruce protocol and during recovery in 3,045 Framingham Study subjects (mean age 43 years; 53% women). The association between exercise BP and CVD events during 20 years of follow-up was examined using Cox proportional hazards models. In age- and sex-adjusted analyses, exercise systolic and diastolic BP were associated with incident CVD (adjusted hazard ratios [HRs] for top quintile 1.55, 95% confidence interval [CI] 1.18 to 2.04; and 1.77, 95% CI 1.35 to 2.31, respectively, relative to the lower 4 quintiles; p <0.005). After adjustment for BP at rest and conventional risk factors, exercise diastolic BP (HR 1.41, 95% CI 1.01 to 1.95, p = 0.04), but not exercise systolic BP (HR 0.97, 95% CI 0.68 to 1.38, p = 0.86), remained a significant predictor of CVD. Similarly, in recovery responses after exercise, only diastolic BP (HR 1.53, 95% CI 1.08 to 2.18, p = 0.02) predicted incident CVD in multivariable models. In conclusion, in middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD. Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group.
113 citations
TL;DR: It is reported that exogenous-expression of PLS3 enhances apoptotic death induced by TRAIL by potentiating the mitochondrial arm of the death pathway and it is demonstrated that TRAIL-induced activation of PKC-delta mediates regulation of the P LS3-induced changes in cardiolipin.
Abstract: Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) initiate pathways of cell death in which caspase activation is mediated either directly (without mitochondrial amplification), or indirectly via the release of apoptogenic factors from mitochondria. Phospholipid scramblases (PLS) are enzymes that play a key role in cellular function by inducing bidirectional movement of membrane lipids. Changes in mitochondrial membrane lipids, cardiolipin, are critical for mediating apoptotic response in many cell-types. PLS3 is a phospholipid scramblase that is localized to mitochondria and is thought to be involved in the regulation of apoptotic signals. Here we report that exogenous-expression of PLS3 enhances apoptotic death induced by TRAIL. This is acheived by potentiating the mitochondrial arm of the death pathway. Thereby, PLS3 expression facilitates changes in mitochondrial membrane lipids that promote the release of apoptogenic factors and consequent full activation and processing of the caspase-9 and effector caspase-3. Moreover, we show that knock-down of endogenous PLS3 suppresses TRAIL-induced changes in cardiolipin. Finally, we demonstrate that TRAIL-induced activation of PKC-delta mediates regulation of the PLS3-induced changes in cardiolipin.
38 citations
TL;DR: Evidence is found that BP levels in the community have changed over time, coinciding with improved rates of hypertension control and attenuation of BP-mortality relations, consistent with the hypothesis that hypertension treatment in thecommunity has altered the natural history of BP progression and its relation to clinical outcome.
Abstract: Background Long-term blood pressure (BP) progression and its importance as a predictor of clinical outcome have not been well characterized across different periods. Methods We evaluated period trends for 3 BP variables (long-term slope and mean BP during a baseline period of 16 years, and last baseline value) in an earlier period (1953-1971; n = 1644, mean participant age, 61 years) and in a later period (1971-1990; n = 1040, mean participant age, 58 years) in participants in the Framingham Heart Study who initially did not have hypertension. In addition, we explored the relation of BP to cardiovascular disease incidence and all-cause mortality in the 2 periods, each with up to 16 years of follow-up. Results Long-term slope, mean, and last baseline BP measurements were significantly lower in the later period ( P P P = .03; hazard ratio for diastolic BP, 1.00 vs 1.23, P = .04). Conclusions We found evidence that BP levels in the community have changed over time, coinciding with improved rates of hypertension control and attenuation of BP-mortality relations. These findings are consistent with the hypothesis that hypertension treatment in the community has altered the natural history of BP progression and its relation to clinical outcome.
10 citations