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Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

ABSTRACT: Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.

SUBMITTER: Kaysen GA

PROVIDER: S-EPMC6071781 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

Kaysen George A GA Ye Xiaoling X Raimann Jochen G JG Wang Yuedong Y Topping Alice A Usvyat Len A LA Stuard Stefano S Canaud Bernard B van der Sande Frank M FM Kooman Jeroen P JP Kotanko Peter P

Journal of lipid research 20180612 8

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysi ...[more]

PMID: 29895699

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Project description:Purpose: We aimed to assess the associations of handgrip strength (HS) with cardiovascular and all-cause mortality and whether adding data on HS to cardiovascular disease (CVD) risk factors is associated with improvement in CVD mortality prediction.Design: Handgrip strength was assessed in a population-based sample of 861 participants aged 61-74 years at baseline. Relative HS was obtained by dividing the absolute value by body weight.Results: During a median (interquartile range) follow-up of 17.3 (12.6-18.4) years, 116 fatal coronary heart diseases (CHDs), 195 fatal CVDs and 412 all-cause mortality events occurred. On adjustment for several risk factors, the hazard ratios (95% confidence intervals (CIs)) for fatal CHD, fatal CVD and all-cause mortality were 0.59 (0.37-0.95), 0.59 (0.41-0.86) and 0.66 (0.51-0.84), respectively, comparing extreme tertiles of relative HS. Adding relative HS to a CVD mortality risk prediction model containing established risk factors did not improve discrimination or reclassification using Harrell's C-index (C-index change: 0.0034; p = .65), integrated-discrimination-improvement (0.0059; p = .20) and net-reclassification-improvement (-1.31%; p = .74); however, there was a significant difference in -2 log likelihood (p < .001).Conclusions: Relative HS is inversely associated with CHD, CVD and all-cause mortality events. Adding relative HS to conventional risk factors improves CVD risk assessment using sensitive measures of discrimination.KEY MESSAGESHandgrip strength (HS) assessment is simple, inexpensive and it takes only a few minutes to measure in clinical practice; however, its prognostic role for fatal cardiovascular outcomes on top of traditional risk factors in apparently healthy populations is uncertain.In a population-based prospective cohort study, good HS adjusted for body weight was associated with lower risk of fatal cardiovascular outcomes and the associations remained consistent across several clinically relevant subgroups.Handgrip strength may be a useful prognostic tool for fatal CHD and CVD events, in the general population.

Project description:Examination of host genome-wide changes upon encounters with pathogens provides insight into the pathogenesis of infection and disease. When performed comparatively, it may shed light on the mechanisms underlying host susceptibility. In this study, gene expression in the mouse colon was investigated in two cognate lines of mice that differ in their response to Citrobacter rodentium infection; susceptible inbred FVB/N (FVB) and resistant outbred Swiss Webster (SW) mice. Gene expression in the distal colon was investigated prior to infection and at 4 and 9 days post-inoculation using a whole mouse genome Affymetrix array. Computational analysis identified 462 (1%) probe sets differentially expressed by more than 2-fold between uninoculated SW and FVB mice. In response to C. rodentium infection, 5,123 probe sets (11.4%) were significantly modulated in one or both lines of mice. Microarray data were validated by quantitative real time RT-PCR on 35 selected genes (r = 0.87, p < 0.001) and were found to have a 94% concordance. Transcripts represented by 1,547 probe sets (3.4%), were differentially expressed between FVB and SW mice regardless of infection status (host effect). Genes associated with transport were over-represented to a greater extent than immune response-related genes (25% vs. 11% of enrichment, respectively). Electrolyte analysis revealed hypochloremia and hyponatremia in susceptible animals. The results support the hypothesis that mortality in C. rodentium-infected FVB mice is associated with impaired ion transport and development of fatal hypovolemia. These studies contribute to our understanding of the pathogenesis of C. rodentium and suggest novel strategies for the prevention and treatment of diarrhea associated with bacterial infections of the intestinal tract. Experiment Overall Design: Global gene expression analysis was performed on the distal colon with 2-3 mice per group. Because no difference for any parameters was observed in uninfected mice at 4 or 9 dpi, the animals were pooled into an uninoculated control groups for each line of mouse. The selection of representative samples for microarray analysis was based on known infection status and colonic lesions. The final number of biological replicates for each condition was n = 5 for uninoculated FVB mice (âFpâ group), n = 4 for uninoculated SW mice (âSpâ group), and n = 3 for infected animals from each line at each time point (âFi4â, âSi4â, âFi9â, and âSi9â respectively).

Project description:BackgroundElevated serum phosphorus is associated with all-cause mortality, but little is known about risk associated with dietary phosphorus intake.ObjectiveWe investigated the association between phosphorus intake and mortality in a prospective cohort of healthy US adults (NHANES III; 1998-1994).DesignStudy participants were 9686 nonpregnant adults aged 20-80 y without diabetes, cancer, or kidney or cardiovascular disease. Exposure to dietary phosphorus, which was assessed by using a 24-h dietary recall, was expressed as the absolute intake and phosphorus density (phosphorus intake divided by energy intake). All-cause and cardiovascular mortality was assessed through 31 December 2006.ResultsMedian phosphorus intake was 1166 mg/d (IQR: 823-1610 mg/d); median phosphorus density was 0.58 mg/kcal (0.48-0.70 mg/kcal). Individuals who consumed more phosphorus-dense diets were older, were less often African American, and led healthier lifestyles (smoking, physical activity, and Healthy Eating Index). In analyses adjusted for demographics, cardiovascular risk factors, kidney function, and energy intake, higher phosphorus intake was associated with higher all-cause mortality in individuals who consumed >1400 mg/d [adjusted HR (95% CI): 2.23 (1.09, 4.5) per 1-unit increase in ln(phosphorus intake); P = 0.03]. At <1400 mg/d, there was no association. A similar association was seen between higher phosphorus density and all-cause mortality at a phosphorus density amount >0.35 mg/kcal [adjusted HR (95% CI): 2.27 (1.19, 4.33) per 0.1-mg/kcal increase in phosphorus density; P = 0.01]. At <0.35 mg/kcal (approximately the fifth percentile), lower phosphorus density was associated with increased mortality risk. Phosphorus density was associated with cardiovascular mortality [adjusted HR (95% CI): 3.39 (1.43, 8.02) per 0.1 mg/kcal at >0.35 mg/kcal; P = 0.01], whereas no association was shown in analyses with phosphorus intake. Results were similar by subgroups of diet quality and in analyses adjusted for sodium and saturated fat intakes.ConclusionsHigh phosphorus intake is associated with increased mortality in a healthy US population. Because of current patterns in phosphorus consumption in US adults, these findings may have important public health implications.

Project description:BackgroundHigh concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ?80 y (oldest old) remains unclear.ObjectiveWe investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ?80 y.DesignThe present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs.ResultsThe median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases.ConclusionsA higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ?80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.

Project description:BackgroundFew longitudinal studies have investigated the association between foods/dietary pattern and mortality risk in the Asian population. We investigated the prospective association between foods/dietary pattern and risk of death among ethnic Chinese adults in Taiwan.MethodsThe study population included 2475 young and middle-aged adults (aged 18-65 years at baseline) who completed the questionnaires and physical examinations in the Nutrition and Health Survey in Taiwan from 1993 to 1996. A food frequency questionnaire was administered to assess food consumption habits in a face-to-face interview. With survey data linked to the Taiwanese Death Registry, Cox proportional hazard model was used to identify the foods associated with all-cause mortality(followed until 2012), which were then tallied to calculate a dietary pattern score called Taiwanese Eating Approach(TEA) score. The TEA scores were then associated with various kinds of mortality outcomes. In addition, data from 431 elders (aged≥65 yrs) with 288 death endpoints were used to conduct a sensitivity analysis.ResultsA total of 385(15.6%) participants died (111 cardiovascular related deaths and 122 cancer related deaths) during the 17.8-year follow-up period(41274 person-years). Twelve foods (9 inverse [vegetables/fish/milk/tea](+1) and 3 positive[fatty meats/fermented vegetables/sweet drinks](-1)) were significantly associated with all-cause mortality risk. All adults were grouped by their cumulative food score into three diet groups: poor diet(29.3% of all subjects), average diet(44.0%), and healthy diet(26.70%). The better the diet, the lower the total, cardiovascular, and other cause mortality outcomes (trend-p < .001). The hazard ratio for the healthy diet was 0.64 (95% confidence interval:0.47-0.87) for total mortality, and 0.52(0.28-0.95) for cardiovascular death, compared with the poor diet in the multivariable models. This phenomenon was also seen in older adults for all-cause, cancer, and other cause mortalities.ConclusionConsuming a healthy Taiwanese Eating Approach (TEA) diet is negatively associated with all-cause, cardiovascular, and other-cause mortalities in Taiwan.

Dataset Information

Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

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Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

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