Serum leptin, C-reactive protein, and cancer mortality in the NHANES III.
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ABSTRACT:
SUBMITTER: Wulaningsih W
PROVIDER: S-EPMC4708908 | biostudies-other | 2016 Jan
REPOSITORIES: biostudies-other
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Project description:Multi-systemic biological risk (MSBR), a proxy for allostatic load, is a composite index of biomarkers representing dysregulation due to responses to chronic stress. This study examined the association of an MSBR index with cancer mortality. The sample included n = 13,628 adults aged 20-90 from the NHANES III Linked Mortality File (1988-1994). The MSBR index included autonomic (pulse rate, blood pressure), metabolic (HOMAir, triglycerides, waist circumference), and immune (white blood cell count, C-reactive protein) markers. We fit Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of overall cancer mortality risk, according to quartiles (q) of the index. In multivariable models, compared to those in q1, q4 had a 64% increased risk for cancer mortality (HR = 1.64, 95% CI:1.13-2.40). The immune domain drove the association (HR per unit = 1.19, 95% CI:1.07-1.32). In stratified analyses, the HR for those with a BMI ≥ 25 was 1.12 per unit (95% CI:1.05-1.19) and those with a BMI < 25 was 1.04 per unit (95% CI:0.92-1.18). MSBR is positively associated with risk for cancer mortality in a US sample, particularly among those who are overweight or obese. The utilization of standard clinical measures comprising this index may inform population cancer prevention strategies.
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Project description:Pre-clinical studies link cannabinoid-1 receptor activation to inflammation and atherosclerotic effects; anti-inflammation and immunosuppression seem to be mediated by cannabinoid-2 receptor activation. In this epidemiological study, we aim to present estimates on suspected cannabis-attributable immunomodulation as manifest in serum C-reactive protein (CRP) levels as non-specific inflammatory markers with interpretable clinical values. With strength of data from recent large nationally representative community sample surveys, the research approach illustrates value of a quantile regressions approach in lieu of the commonly used but relatively arbitrary cutpoints for CRP values.The study population encompasses 20-59 year old participants from the National Health and Nutrition Examination Surveys, 2005-2010 (n=1115 recently active cannabis smokers and 8041 non-smokers, identified via confidential Audio Computer Assisted Self-Interviews). Age, sex, race, education, income-poverty ratio, alcohol consumption, and tobacco smoking also were measured, together with body mass index (BMI), which actually might be on a mediational path. Quantile regressions, with bootstrapping for variance estimation, made it possible to hold these covariates constant while estimating cannabis-CRP associations.Evidence suggesting possible cannabis-attributable immunomodulation emerges at CRP levels below the median (p<0.05). Whereas BMI might help explain a cannabis link with serum CRP, but BMI-stratified analyses disclosed no appreciable variation of the cannabis-CRP relationship across BMI subgroups.Extending pre-clinical research on cannabis-attributable immunomodulation, this study's CRP evidence points toward possible anti-inflammatory effects of cannabis smoking. More definitive evidence can be derived by combining pre-clinical research, studies of patients, and epidemiological research approaches.
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Project description:A reliable, widely available method to detect osteoporosis prior to fracture is needed. Serum levels of C-reactive protein may independently predict low bone mineral density (BMD) and high fracture risk. Existing empirical data focus on sexually and/or racially homogenous populations. This study tests the hypotheses that: C-reactive protein (1) negatively correlates with BMD and (2) fracture history, and (3) independently predicts BMD and fracture history in a diverse population. NHANES 2017-2020 pre-pandemic cycle data were analyzed in R studio. Strength and direction of relationships (-1 to +1) between variables were determined using Kendall's rank correlation coefficient (τ). Linear models were optimized to predict femoral neck or lumbar spine BMD. C-reactive protein positively correlated with femoral (τ = 0.09, p<0.0001) and spine BMD (τ = 0.10, p<0.0001). Individuals identifying as female demonstrated more robust, but still weak, correlations between C-reactive protein and femoral neck (τ = 0.15, p<0.0001; male, τ = 0.06, p = 0.051) and spine BMD (τ = 0.16, p<0.0001; male, τ = 0.06, p = 0.04). C-reactive protein positively correlated with fracture history (τ = 0.083, p = 0.0009). C-reactive protein significantly predicted femoral neck (R2 = 0.022, p = 0.0001) and spine BMD (R2 = 0.028, p<0.0001) and fracture history (R2 = 0.015, p<0.0001). Exploratory analyses identified weight was the single best predictor for femoral neck (R2 = 0.24, p<0.0001) and spine BMD (R2 = 0.21, p<0.0001). In sum, C-reactive protein statistically correlates with and predicts femoral neck and spine BMD, but the magnitude is too low to be biologically meaningful. While weight is a more robust predictor, individuals who are overweight or obese account for nearly half of all osteoporotic fractures, limiting the predictive power of this variable at identifying individuals at risk for osteoporosis. Identification of a robust predictor of fracture risk in a diverse population and across of range of body weights and compositions is needed.
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Project description:BackgroundC-reactive protein (CRP) is an acute phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker used for following the progression and resolution of infection. We aimed to determine the association of baseline CRP level and the temporal change in CRP over time with cryptococcal meningitis outcome.MethodsWe reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline plasma CRP collected within 5 days of meningitis diagnosis was categorized into quartiles. We compared baseline CRP with 18-week survival using time-to-event analysis.ResultsOf 168 participants, the baseline first quartile of serum CRP was <29.0 mg/L, second quartile 29.0-49.5 mg/L, third quartile 49.6-83.6 mg/L, and fourth quartile >83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by CRP quartile. Participants with CRP >49.5 mg/L more likely presented with Glasgow Coma Scale (GCS) <15 (P?=?.03). The 18-week mortality rate was 55% (46/84) in the highest 2 quartile CRP groups (>49.5 mg/L), 41% (17/42) in the mid-range CRP group (29.0-49.5 mg/L), and 14% (6/42) in the low-CRP group (<29.0 mg/L; P?<?.001). After adjustment for possible confounding factors including GCS?<15, CRP remained significantly associated with mortality (adjusted hazard ratio, 1.084 per 10 mg/L; 95% CI, 1.031-1.139; P?=?.0016).ConclusionsHigher baseline CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. CRP could be a surrogate marker for undiagnosed coinfections or may reflect immune dysregulation, leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis.
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Project description:BackgroundThere is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortality, while taking into account demographic and lifestyle factors and significant other diseases which are known to be associated with poorer outcome.MethodsThe main outcomes of our study were all-cause mortality, cardiovascular mortality, and cancer-related mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2015. The association of serum B12 concentrations and vitamin B12 supplement intake with mortality was assessed with Cox proportional hazard (PH) models, with adjustment for a number of relevant demographic and lifestyle factors and comorbidity.ResultsThe final study population of 24,262 participants had a mean age of 48 (SD 19) years; 50.1% were males. The median follow-up duration was 109 months (range 1-201 months). On the census day of December 31, 2015, 3023 participants were determined as deceased (12.5%). The fully adjusted Cox PH model indicated that low serum B12 concentrations < 140 pmol/l were associated with a small increase in all-cause (hazard ratio, HR 1.39, 95% CI 1.08-1.78, p = 0.011) and cardiovascular (HR 1.64, 95% CI 1.08-2.47, p = 0.020) mortality. Similarly, high serum B12 concentrations > 700 pmol/l were associated with an increase in cardiovascular mortality only (HR 1.45, 95% CI 1.01-2.06, p = 0.042). Participants with a diagnosis of hypertension, dyslipidemia, CVD, and cancer more frequently used vitamin B12-containing supplements than those without these diagnoses. We could not demonstrate an association between vitamin B12 supplement intake and mortality, when adjusted for comorbidity.ConclusionsIn the general population of NHANES, low serum B12 concentrations were associated with a moderate increase in all-cause mortality. There was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. High intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe.
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Project description:Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case-control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the ORs and 95% confidence intervals (CI) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 cases and 706 controls were matched on ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, hours fasting before blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin [ORQ4 vs. Q1, 1.94 (1.37-2.75); Ptrend ? 0.001), the leptin:adiponectin ratio [OR, 1.91 (1.36-2.68); Ptrend = 0.005], and CRP [OR, 1.41 (1.01-1.96); Ptrend = 0.014] were associated with an increased risk of postmenopausal breast cancer. The positive associations for these markers remained after adjustment for body mass index (BMI). No associations were detected for adiponectin. These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI. Further prospective studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted. Cancer Prev Res; 6(3); 188-95. ©2013 AACR.
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Project description:Higher serum total alkaline phosphatase (AP) levels are associated with increased serum C-reactive protein (CRP) levels and mortality in the general and CKD populations. It is unclear to what extent these associations are related to bone disease.In a nationally representative sample of 10,707 adult participants from the 1999-2004 National Health and Nutrition Examination Survey, serum nonskeletal AP levels were estimated from the measured serum skeletal and total AP levels. The associations of serum skeletal AP and nonskeletal AP levels with elevated serum CRP concentrations (>3 mg/L) and mortality were examined in multivariable models.Skeletal AP was not associated with elevated CRP (for each doubling in non-CKD: odds ratio [OR], 1.00; 95% confidence interval [95% CI], 0.90-1.11; in CKD: OR, 1.19; 95% CI, 0.83-1.70) or mortality (for each doubling in non-CKD: hazard ratio [HR], 1.10; 95% CI, 0.94-1.29; in CKD: HR, 0.98; 95% CI, 0.75-1.28). In contrast, nonskeletal AP was associated with elevated CRP (for each doubling in non-CKD: OR, 4.51; 95% CI, 3.80-5.35; in CKD: OR, 5.98; 95% CI, 3.40-10.51). Nonskeletal AP was associated with mortality in non-CKD (for each doubling: HR, 1.96; 95% CI, 1.37-2.80) but not in CKD (for each doubling: HR, 0.92; 95% CI, 0.51-1.67) (interaction P=0.03).Bone disease is unlikely to account for the known associations of serum total AP with increased inflammation and mortality.
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Project description:Elevated levels of serum leptin are associated with increased adiposity and production of pro-inflammatory cytokines. Both cytokines and body adiposity have been shown to predict cardiovascular events and mortality. The primary objective of the present study is to explore the associations between serum leptin and all-cause mortality and mortality from cardiovascular disease (CVD) over a span of 10 years, controlling for body adiposity and proinflammatory cytokines.The Health, Aging and Body Composition (Health ABC) study is a prospective cohort of 3,075 older adults aged 70 to 79 years. This analysis includes 2,919 men and women with complete serum leptin and vital status data. Data on all-cause mortality and incident cardiovascular events (including Coronary Heart Disease and Congestive Heart Failure) were collected over 10 years of follow-up (mean 8.4 years).Women with leptin in quartile 2 and 3 were at lower risk of all-cause mortality, and those with leptin in quartile 2 were at lower risk of mortality from CVD as compared to women with lowest leptin values when adjusted for age, race, site, years of education, alcohol use, smoking, and physical activity. When these associations were additionally adjusted for body fat, C-reactive protein and pro-inflammatory cytokines, women with leptin values in quartile 3 were at lower risk of all-cause mortality and women with leptin in quartile 2 and 3 were at lower risk of mortality from CVD than women with lowest leptin values. These associations were not significant among men after adjusting for body fat and cytokines.The present study suggests that moderately elevated concentrations of serum leptin are independently associated with lower risk of all-cause mortality and CVD-related mortality among older women. Among men, serum leptin is not associated with reduced risk of all-cause and CVD mortality after controlling for body fat and cytokines.
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