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The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality.

ABSTRACT: Moderately elevated levels of plasma plant sterols have been suspected to be causally involved in atherosclerosis. The aim of this study was to investigate whether plant sterols and other markers of sterol metabolism predicted all-cause and cardiovascular mortality in participants of the Ludwigshafen Risk and Cardiovascular health (LURIC) study. A total of 1,257 individuals who did not use statins and at baseline had a mean (+/- SD) age of 62.8 (+/- 11.0) years were included in the present analysis. Lathosterol, cholestanol, campesterol, and sitosterol were measured to estimate cholesterol synthesis and absorption. The mean (+/- SD) time of the follow-up for all-cause and cardiovascular mortality was 7.32 (+/- 2.3) years. All-cause (P = 0.001) and cardiovascular (P = 0.006) mortality were decreased in the highest versus the lowest lathosterol to cholesterol tertile. In contrast, subjects in the third cholestanol to cholesterol tertile had increased all-cause (P < 0.001) and cardiovascular mortality (P = 0.010) compared with individuals in the first tertile. The third campesterol to cholesterol tertile was associated with increased all-cause mortality (P = 0.025). Sitosterol to cholesterol tertiles were not significantly related to all-cause or cardiovascular mortality. The data suggest that high absorption and low synthesis of cholesterol predict increased all-cause and cardiovascular mortality in LURIC participants.

SUBMITTER: Silbernagel G

PROVIDER: S-EPMC2903788 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality.

Silbernagel Guenther G Fauler Guenter G Hoffmann Michael M MM Lütjohann Dieter D Winkelmann Bernhard R BR Boehm Bernhard O BO März Winfried W

Journal of lipid research 20100314 8

Moderately elevated levels of plasma plant sterols have been suspected to be causally involved in atherosclerosis. The aim of this study was to investigate whether plant sterols and other markers of sterol metabolism predicted all-cause and cardiovascular mortality in participants of the Ludwigshafen Risk and Cardiovascular health (LURIC) study. A total of 1,257 individuals who did not use statins and at baseline had a mean (+/- SD) age of 62.8 (+/- 11.0) years were included in the present analy ...[more]

PMID: 20228406

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Project description:The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols.We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method.The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker.Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol absorption inhibition with STAEST. Serum plant sterol concentrations decrease dose-dependently in response to plant stanols suggesting that the higher the plant stanol dose, the more cholesterol absorption is inhibited and the greater the reduction in LDL cholesterol level is that can be achieved.Clinical Trials Register # NCT00698256 [Eur J Nutr 2010, 49:111-117].

Project description:ImportanceCholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial.ObjectiveTo determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality.Design, setting, and participantsIndividual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol.ExposuresDietary cholesterol (mg/day) or egg consumption (number/day).Main outcomes and measuresHazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors.ResultsThis analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, -0.47% [95% CI, -1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, -0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption.Conclusions and relevanceAmong US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

Project description:BackgroundBlood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target <120 mmHg. However, all-cause mortality by attained BP in routine care in frail adults aged above 75 is unclear.ObjectivesTo estimate observational associations between baseline BP and mortality/cardiovascular outcomes in a primary-care population aged above 75, stratified by frailty.MethodsProspective observational analysis using electronic health records (clinical practice research datalink, n = 415,980). We tested BP associations with cardiovascular events and mortality using competing and Cox proportional-hazards models respectively (follow-up ≤10 years), stratified by baseline electronic frailty index (eFI: fit (non-frail), mild, moderate, severe frailty), with sensitivity analyses on co-morbidity, cardiovascular risk and BP trajectory.ResultsRisks of cardiovascular outcomes increased with SBPs >150 mmHg. Associations with mortality varied between non-frail <85 and frail 75-84-year-olds and all above 85 years. SBPs above the 130-139-mmHg reference were associated with lower mortality risk, particularly in moderate to severe frailty or above 85 years (e.g. 75-84 years: 150-159 mmHg Hazard Ratio (HR) mortality compared to 130-139: non-frail HR = 0.94, 0.92-0.97; moderate/severe frailty HR = 0.84, 0.77-0.92). SBP <130 mmHg and Diastolic(D)BP <80 mmHg were consistently associated with excess mortality, independent of BP trajectory toward the end of life.ConclusionsIn representative primary-care patients aged ≥75, BP <130/80 was associated with excess mortality. Hypertension was not associated with increased mortality at ages above 85 or at ages 75-84 with moderate/severe frailty, perhaps due to complexities of co-existing morbidities. The priority given to aggressive BP reduction in frail older people requires further evaluation.

Project description:Background and objectivesFluid removal via ultrafiltration is a primary function of hemodialysis, and inadequate volume control is associated with significant morbidity and mortality among chronic dialysis patients. Treatment-to-treatment fluid removal goals are typically calculated on the basis of interdialytic weight gain and prescribed target weight. The clinical effect of frequent missed target weights is unclear. This study was designed to evaluate the associations of postdialysis weights above and below the prescribed target weight (separately) and outcomes.Design, setting, participants, & measurementsData were taken from a national cohort of 10,785 prevalent, thrice-weekly, in-center hemodialysis patients dialyzing from 2005 to 2008 (median time at risk, 2.1 [25th percentile, 75th percentile] years) at a single dialysis organization. Patients were characterized as having an above target weight miss if their postdialysis weight was >2 kg above target weight in at least 30% of baseline treatments (14.6% of cohort), or they were characterized as control otherwise. Below target weight miss characterization was analogous for patients with postdialysis weight >2 kg below target weight (6.6% of cohort). Coprimary endpoints were all-cause and cardiovascular mortality.ResultsAbove target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.28; 95% confidence interval, 1.15 to 1.43); and below target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05 to 1.40). Both above and below target weight misses were also significantly associated with greater cardiovascular mortality. Secondary analyses demonstrated dose-response relationships between target weight misses and mortality. Results from sensitivity analyses considering the difference in postdialysis and target weights as a proportion of body weight were analogous to the primary results.ConclusionsPostdialysis weights >2 kg above and below target weight are associated with higher all-cause and cardiovascular mortality. Consistent target weight achievement is a viable target for improving fluid management.

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The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality.

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The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality.

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