Predicting mortality with biomarkers: a population-based prospective cohort study for elderly Costa Ricans.
ABSTRACT: Little is known about adult health and mortality relationships outside high-income nations, partly because few datasets have contained biomarker data in representative populations. Our objective is to determine the prognostic value of biomarkers with respect to total and cardiovascular mortality in an elderly population of a middle-income country, as well as the extent to which they mediate the effects of age and sex on mortality.This is a prospective population-based study in a nationally representative sample of elderly Costa Ricans. Baseline interviews occurred mostly in 2005 and mortality follow-up went through December 2010. Sample size after excluding observations with missing values: 2,313 individuals and 564 deaths.prospective death rate ratios for 22 baseline biomarkers, which were estimated with hazard regression models.Biomarkers significantly predict future death above and beyond demographic and self-reported health conditions. The studied biomarkers account for almost half of the effect of age on mortality. However, the sex gap in mortality became several times wider after controlling for biomarkers. The most powerful predictors were simple physical tests: handgrip strength, pulmonary peak flow, and walking speed. Three blood tests also predicted prospective mortality: C-reactive protein (CRP), glycated hemoglobin (HbA1c), and dehydroepiandrosterone sulfate (DHEAS). Strikingly, high blood pressure (BP) and high total cholesterol showed little or no predictive power. Anthropometric measures also failed to show significant mortality effects.This study adds to the growing evidence that blood markers for CRP, HbA1c, and DHEAS, along with organ-specific functional reserve indicators (handgrip, walking speed, and pulmonary peak flow), are valuable tools for identifying vulnerable elderly. The results also highlight the need to better understand an anomaly noted previously in other settings: despite the continued medical focus on drugs for BP and cholesterol, high levels of BP and cholesterol have little predictive value of mortality in this elderly population.
Project description:OBJECTIVE:To determine the prognostic value of cortisol, Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone-sulfate (DHEAS), together with their ratios (cortisol/DHEA and cortisol/DHEAS), as independent predictors of mortality in septic patients. METHODS:Prospective cohort study of 139 consecutive patients with a diagnosis of severe sepsis or septic shock. Adrenal hormones were determined within the first 24 hours of the septic process. To determine and compare the predictive ability of each marker for the risk of unfavorable evolution (in-hospital, 28-day and 90-day mortality), ROC (Receiver Operating Characteristic) curves were constructed and the area under the curve (AUC) was determined. As measures of association, adjusted odds ratios (OR) with their 95% confidence intervals (95%CI) were estimated by unconditional logistic regression. Cortisol, DHEA and DHEAS results were compared to lactate, CRP, SOFA and APACHE II Scores. RESULTS:Cortisol showed the best predictive ability, with AUCs of 0.758, 0.759 and 0.705 for in-hospital mortality, and 28-day and 90-day mortality, respectively; whereas AUCs for 28 days mortality for SOFA and APACHE II scores, and other biomarkers studied, such as Lactate or CRP, were 0.644, 0.618, 0.643 and 0.647, respectively. Associations between high cortisol levels (>17.5 ?g/dL) and mortality were strong and statistically significant for in-hospital and 28-day mortality: adjusted ORs 10.13 and 9.45 respectively, and lower for long term mortality (90 days): adjusted OR 4.26 (95% CI 1.34-13.56), p trend 0.014. Regarding adrenal androgens, only positive associations were obtained for DHEAS and most of these positive associations did not yield statistical significance. Regarding Cortisol/DHEA and cortisol/DHEAS ratios, they did not improve the predictive ability of cortisol. The only exception was the cortisol/DHEAS ratio, which was the best predictor of mortality at 90 days (AUC 0.737), adjusted OR for highest cortisol/DHEAS ratio values 6.33 (95%CI 1.77-22.60), p trend 0.002. CONCLUSION:Basal cortisol measured within the first 24 hours of the septic process was the best prognostic factor for in-hospital and 28-day mortality, even superior to the Sequential Organ Failure Assessment (SOFA) or Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. The cortisol/DHEAS ratio was an independent predictor of long-term mortality.
Project description:Few studies have evaluated the relationships between intake of sugar-sweetened beverages (SSB) and intermediate biomarkers of cardiometabolic risk. Associations between artificially sweetened beverages (ASB) and fruit juice with cardiometabolic biomarkers are also unclear. We investigated habitual SSB, ASB and fruit juice intake in relation to biomarkers of hepatic function, lipid metabolism, inflammation and glucose metabolism. We analysed cross-sectional data from 8492 participants in the Nurses' Health Study who were free of diabetes and CVD. Multivariate linear regression was used to assess the associations of SSB, ASB and fruit juice intake with concentrations of fetuin-A, alanine transaminase, ?-glutamyl transferase, TAG, HDL-cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein (CRP), intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1, adiponectin, insulin and HbA1c as well as total cholesterol:HDL-cholesterol ratio. More frequent intake of SSB was significantly associated with higher concentrations of fetuin-A, TAG, CRP, ICAM-1, adiponectin and insulin, a higher total cholesterol:HDL-cholesterol ratio, and a lower concentration of HDL-cholesterol (P trend ranges from <0·0001 to 0·04) after adjusting for demographic, medical, dietary and lifestyle variables. ASB intake was marginally associated with increased concentrations of CRP (P trend=0·04) and adiponectin (P trend=0·01). Fruit juice intake was associated with increased concentrations of TAG and HbA1c and a lower concentration of adiponectin (P trend ranges from <0·0001 to 0·01). In conclusion, habitual intake of SSB was associated with adverse levels of multiple cardiometabolic biomarkers. Associations between ASB and fruit juice with cardiometabolic risk markers warrant further exploration.
Project description:Although age-related declines in dehydroepiandrosterone sulfate (DHEAS) and testosterone are associated with cardiovascular risk, it remains to be determined whether replacement of these hormones improves cardiovascular risk factors.This study sought to determine the effect of long-term replacement of dehydroepiandrosterone (DHEA) in elderly men and women and testosterone in elderly men on lipid and lipoprotein concentrations and particle sizes.A 2-yr randomized, placebo-controlled, double-blind study was conducted in 87 elderly men with low levels of DHEAS and bioavailable testosterone and 57 elderly women with low levels of DHEAS. Among elderly men, 29 received DHEA (75 mg/d), 27 received testosterone (5 mg/d), and 31 received placebo. Among the elderly women, 27 received DHEA (50 mg/d), and 30 received placebo. Baseline lipoprotein profiles in the elderly were compared to healthy younger participants. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle sizes and concentrations were quantified using nuclear magnetic resonance spectroscopy.The elderly had higher concentrations of total cholesterol, triglycerides, LDL cholesterol, total LDL particles, and small, dense LDL particles than the young. In men, neither DHEA nor testosterone affected LDL or HDL particle concentrations. In women, DHEA reduced HDL cholesterol [median difference (95% confidence intervals), -5.0 (-8.0, -2.0) mg/dl; P = 0.002] and the number of large HDL particles [-1.0 (-1.8, -0.2) micromol/liter; P = 0.003].Long-term DHEA and testosterone had no significant effect on plasma lipoproteins in elderly men, but elderly women showed a lowering of the large HDL particles that may have potential adverse clinical implications.
Project description:The association of hypertension and mortality is attenuated in elderly adults. Walking speed, as a measure of frailty, may identify which elderly adults are most at risk for the adverse effects of hypertension. We hypothesized that elevated blood pressure (BP) would be associated with a greater risk of mortality in faster-, but not slower-, walking older adults.Participants included 2340 persons 65 years and older in the National Health and Nutrition Examination Survey, 1999-2000 and 2001-2002. Mortality data were linked to death certificates in the National Death Index. Walking speed was measured over a 20-ft (6 m) walk and classified as faster (? 0.8 m/s [n = 1307]), slower (n = 790), or incomplete (n = 243). Potential confounders included age, sex, race, survey year, lifestyle and physiologic variables, health conditions, and antihypertensive medication use.Among the participants, there were 589 deaths through December 31, 2006. The association between BP and mortality varied by walking speed. Among faster walkers, those with elevated systolic BP (? 140 mm Hg) had a greater adjusted risk of mortality compared with those without (hazard ratio [HR], 1.35; 95% CI, 1.03-1.77). Among slower walkers, neither elevated systolic nor diastolic BP (? 90 mm Hg) was associated with mortality. In participants who did not complete the walk test, elevated BP was strongly and independently associated with a lower risk of death: HR, 0.38; 95% CI, 0.23-0.62 (systolic); and HR, 0.10; 95% CI, 0.01-0.81 (diastolic).Walking speed could be a simple measure to identify elderly adults who are most at risk for adverse outcomes related to high BP.
Project description:A Follow-up of vitamin B12 and lipids status is essential in older people, being closely related to non-communicable diseases. Their relationships with cognitive and physical status are not clear. The aim was to analyze the evolution of vitamin B12 and related parameters, lipid and hematological profiles, and their relationships with cognitive and physical status among institutionalized elderly. Sixty residents, ranged from 62 to 99, were evaluated. Biomarkers (vitamin B12 and related parameters, lipid and hematological profiles), functional capacity (handgrip, arm and leg strength), and cognitive status (Mini-Mental State Examination) were evaluated four times at 4-month intervals. At the beginning of the study, 63% and 70% of the sample showed abnormal homocysteine and folate values, respectively. At the end of the year, abnormal homocysteine increased to 68%, abnormal folate values decreased to 50%. Throughout the year, serum folate showed a significant increase (14.9 vs. 16.3 nmol/L), (p < 0.05). Serum cobalamin (299 vs. 273 pmol/L). HDL-cholesterol (49.9 vs. 47.0 mg/dL) and triglyceride levels (102.4 vs. 123.2 mg/dL) showed a significant decrease and increase respectively in mean values (all p < 0.05). Serum cobalamin and HDL-cholesterol were the most important biomarkers associated with cognitive function (both p < 0.05). The most relevant biomarkers associated with poor physical strength depending on the body part analyzed were low concentrations of HDL-cholesterol, LDL-cholesterol, apolipoprotein A1, and albumin (all p < 0.05). The evolution of lipid biomarkers, their significance with cognitive values, and association with handgrip, point to the importance of the handgrip measurement, a very simple test, as an important health marker. Both serum albumin and physical strength are important health markers in older people.
Project description:AIMS/HYPOTHESIS:Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the ratio of DHEAS to DHEA, and risk of type 2 diabetes. METHODS:We used data on serum levels of DHEA, DHEAS and androstenedione from 5189 middle-aged and elderly men and women from the prospective population-based Rotterdam Study. Type 2 diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a non-fasting blood glucose ≥11.1 mmol/l. RESULTS:During a median follow-up of 10.9 years, 643 patients with incident type 2 diabetes were identified. After adjusting for age, sex, cohort, fasting status, fasting glucose and insulin, and BMI, both serum DHEA levels (per 1 unit natural log-transformed, HR 0.76, 95% CI 0.67, 0.87) and serum DHEAS levels (per 1 unit natural log-transformed, HR 0.82, 95% CI 0.73, 0.92) were inversely associated with risk of type 2 diabetes in the total population. Further adjustment for alcohol, smoking, physical activity, prevalent cardiovascular disease, serum total cholesterol, use of lipid-lowering medications, systolic BP, treatment for hypertension, C-reactive protein, oestradiol and testosterone did not substantially affect the association between DHEA and incident type 2 diabetes (per 1 unit natural log-transformed, HR 0.80, 95% CI 0.65, 0.99), but abolished the association between DHEAS and type 2 diabetes. Androstenedione was not associated with risk of type 2 diabetes, nor was DHEAS to DHEA ratio. CONCLUSIONS/INTERPRETATION:DHEA serum levels might be an independent marker of type 2 diabetes.
Project description:OBJECTIVE:To evaluate achievement of comprehensive controls among patients with type 2 diabetes mellitus (T2DM) in different age groups. RESULTS:The elderly patients had higher control rates for BMI (44.36%), TC (50.83%) and LDL-C (48.27%) than those aged 60-80 years and younger patients (all P <0.05). Multiple logistic regression revealed that elderly patients were more likely to achieve control targets for HbA1c (odd ratio (OR) = 2.19), TC (OR = 1.32), HDL-C (OR = 1.35), and TG (OR = 1.74) than younger patients. This effect was stronger in males (ORHbA1c = 2.27; ORTC = 1.41; ORHDL-C = 1.51; ORTG = 1.80). By contrast, elderly females were only more likely to achieve HbA1c < 7.0% (OR=1.88). CONCLUSIONS:Our findings suggest that comprehensive control strategies still should be strengthened. METHODS:A total of 3126 T2DM patients were included, and detected blood pressure (BP), body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). We divided patients into three age groups (<60, 60-80 and ? 80 years), to assess the differences in achieving the control targets.
Project description:To quantify the association of self-reported walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality.A total of 230?670 women and 190?057 men free from prevalent cancer and cardiovascular disease were included from UK Biobank. Usual walking pace was self-defined as slow, steady/average or brisk. Handgrip strength was assessed by dynamometer. Cox-proportional hazard models were adjusted for social deprivation, ethnicity, employment, medications, alcohol use, diet, physical activity, and television viewing time. Interaction terms investigated whether age, body mass index (BMI), and smoking status modified associations. Over 6.3?years, there were 8598 deaths, 1654 from cardiovascular disease and 4850 from cancer. Associations of walking pace with mortality were modified by BMI. In women, the hazard ratio (HR) for all-cause mortality in slow compared with fast walkers were 2.16 [95% confidence interval (CI): 1.68-2.77] and 1.31 (1.08-1.60) in the bottom and top BMI tertiles, respectively; corresponding HRs for men were 2.01 (1.68-2.41) and 1.41 (1.20-1.66). Hazard ratios for cardiovascular mortality remained above 1.7 across all categories of BMI in men and women, with modest heterogeneity in men. Handgrip strength was associated with cardiovascular mortality in men only (HR tertile 1 vs. tertile 3?=?1.38; 1.18-1.62), without differences across BMI categories, while associations with all-cause mortality were only seen in men with low BMI. Associations for walking pace and handgrip strength with cancer mortality were less consistent.A simple self-reported measure of slow walking pace could aid risk stratification for all-cause and cardiovascular mortality within the general population.
Project description:It is unclear if changes in proposed circulating biomarkers of aging are strongly correlated to each other or functional change. We tested if biomarker changes track with each other and with functional measures over 9 years in older adults.Dehydroepiandrosterone sulfate (DHEAS), adiponectin, insulin-like growth factor 1 (IGF-1), IGF binding proteins 1 (IGFBP-1) and 3 (IGFBP-3), interleukin-6 (IL-6), cholesterol, and function (gait speed, grip strength, Modified Mini Mental Status Exam [3MSE] and Digit Symbol Substitution Test [DSST] scores) were measured in 1996-1997 and 2005-2006 in the Cardiovascular Health Study All Stars study (N = 901, mean [standard deviation, SD] age 85.3 [3.6] years in 2005-2006). Adjusted Pearson correlations illustrated if biomarkers tracked together. Multivariable linear regression demonstrated if biomarker changes tracked with functional changes.Correlations among biomarker changes were mostly <0.2. In models with each biomarker entered separately, a 1-SD increase biomarker change was associated with change in function as follows: grip strength (DHEAS β = 0.61kg, p = .001; IL-6 β = -0.46kg, p = .012; cholesterol men β = 0.79kg, p = .016); gait speed (DHEAS β = 0.02 meters per second, p = .039; IL-6 β = -0.018 meters per second, p = .049); and DSST score (DHEAS women β = 1.46, p = .004; IL-6 β = -0.83, p = .027). When biomarkers were entered in the same model, significant associations remaining were as follows: grip strength (DHEAS β = 0.54kg, p = .005; IL-6 β = -0.43kg, p = .022); 3MSE score (IGF-1 β = 0.96, p = .04; IGFBP-3 β = -1.07, p = .024); and DSST score (DHEAS women β = 1.27, p = .012; IL-6 β = -0.80, p = .04).Changes in biomarkers were poorly correlated, supporting a model of stochastic, independent change across systems. DHEAS and IL-6 tracked most closely with function, illustrating that changes in inflammation and sex steroids may play dominant roles in changes of these functional outcomes.
Project description:The relationship between physical fitness and risk markers for type 2 diabetes (T2D) in children and the contribution to ethnic differences in these risk markers have been little studied. We examined associations between physical fitness and early risk markers for T2D and cardiovascular disease in 9- to 10-year-old UK children.Cross-sectional study of 1445 9- to 10-year-old UK children of South Asian, black African-Caribbean and white European origin. A fasting blood sample was used for measurement of insulin, glucose (from which homeostasis model assessment [HOMA]-insulin resistance [IR] was derived), glycated hemoglobin (HbA1c), urate, C-reactive protein (CRP), and lipids. Measurements of blood pressure (BP) and fat mass index (FMI) were made; physical activity was measured by accelerometry. Estimated VO2 max was derived from a submaximal fitness step test. Associations were estimated using multilevel linear regression.Higher VO2 max was associated with lower FMI, insulin, HOMA-IR, HbA1c, glucose, urate, CRP, triglycerides, LDL-cholesterol, BP and higher HDL-cholesterol. Associations were reduced by adjustment for FMI, but those for insulin, HOMA-IR, glucose, urate, CRP, triglycerides and BP remained statistically significant. Higher levels of insulin and HOMA-IR in South Asian children were partially explained by lower levels of VO2max compared to white Europeans, accounting for 11% of the difference.Physical fitness is associated with risk markers for T2D and CVD in children, which persist after adjustment for adiposity. Higher levels of IR in South Asians are partially explained by lower physical fitness levels compared to white Europeans. Improving physical fitness may provide scope for reducing risks of T2D.