Adjustment For C-reactive Protein Research Articles

Job Strain–Associated Inflammatory Burden and Long-Term Risk of Coronary Events

We examined the association between job strain and coronary heart disease (CHD) and investigated the role of markers of inflammation and endothelial dysfunction as possible mediators of job strain-associated CHD risk. The sample (n = 1027) included employed participants (35-64 years old, 68% male) from the population-based MONICA/KORA (Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg) studies. At baseline Karasek's Job Strain Index was assessed during standardized personal interviews, and nine biological markers were measured (1984-1995). Participants were followed (average, 12 years) to assess incident events (sudden cardiac death or fatal and nonfatal myocardial infarction). In this case-cohort design, the final sample contained 114 cases and 913 noncases. Baseline distributions of cardiometabolic risk factors were significantly different between cases and noncases, with no detectable job strain-specific differences. However, cases with high job strain had higher monocyte chemoattractant protein-1, interleukin (IL)-8, and IL-18 compared with noncases with high job strain. High-sensitivity C-reactive protein, IL-6, and soluble intercellular adhesion molecule-1 were increased in cases versus noncases, regardless of work stress. Job strain was associated with incident coronary events in Cox proportional hazards models adjusted for age, sex, and survey (hazard ratio = 2.57, 95% confidence interval = 1.09-6.07) and after adjustment for CHD risk factors (2.35, 1.003-5.49). Adjustment for monocyte chemoattractant protein-1 or IL-8 increased this risk estimate by 14.5% or 9.4%, respectively, whereas adjustment for C-reactive protein and soluble intercellular adhesion molecule-1 led to decreased hazard ratios (-9.9% and -5.5%, respectively). Job strain increased CHD risk in healthy workers; the associated inflammatory burden may contribute to stress-related coronary pathogenesis.

Leptin and its Association with Somatic Depressive Symptoms in Patients with the Metabolic Syndrome

This study aimed to determine the association between circulating leptin levels and total depressive symptoms as well as depressive symptom dimensions (cognitive and somatic) after controlling for important confounding factors. The study sample was comprised of 135 participants with the metabolic syndrome. Depressive symptoms were measured using the Beck Depression Inventory-II. Leptin was measured using a leptin-specific enzyme immunoassay. Inflammation was assessed using C-reactive protein and interleukin-6 levels. Leptin was significantly associated with somatic depressive symptoms (β = 0.33, P = 0.018), but not total depressive symptoms (β = 0.27, P = 0.067) or cognitive depressive symptoms (β = 0.21, P = 0.182), after controlling for age, gender, body mass index, and insulin resistance. Further adjustment for C-reactive protein and interleukin-6 levels did not alter the relationship (β = 0.32, P = 0.023) between circulating leptin levels and somatic depressive symptoms. Leptin is independently associated with somatic depressive symptoms in patients with the metabolic syndrome.

Plasma bicarbonate and risk of type 2 diabetes mellitus

Several biomarkers of metabolic acidosis, including lower plasma bicarbonate and higher anion gap, have been associated with greater insulin resistance in cross-sectional studies. We sought to examine whether lower plasma bicarbonate is associated with the development of type 2 diabetes mellitus in a prospective study. We conducted a prospective, nested case-control study within the Nurses' Health Study. Plasma bicarbonate was measured in 630 women who did not have type 2 diabetes mellitus at the time of blood draw in 1989-1990 but developed type 2 diabetes mellitus during 10 years of follow-up. Controls were matched according to age, ethnic background, fasting status and date of blood draw. We used logistic regression to calculate odds ratios (ORs) for diabetes by category of baseline plasma bicarbonate. After adjustment for matching factors, body mass index, plasma creatinine level and history of hypertension, women with plasma bicarbonate above the median level had lower odds of diabetes (OR 0.76, 95% confidence interval [CI] 0.60-0.96) compared with women below the median level. Those in the second (OR 0.92, 95% CI 0.67-1.25), third (OR 0.70, 95% CI 0.51-0.97) and fourth (OR 0.75, 95% CI 0.54-1.05) quartiles of plasma bicarbonate had lower odds of diabetes compared with those in the lowest quartile (p for trend = 0.04). Further adjustment for C-reactive protein did not alter these findings. Higher plasma bicarbonate levels were associated with lower odds of incident type 2 diabetes mellitus among women in the Nurses' Health Study. Further studies are needed to confirm this finding in different populations and to elucidate the mechanism for this relation.

Inflammation, iron status, and growth of school‐age children: a prospective study

ObjectiveTo investigate associations of four markers of inflammation, C‐reactive protein (CRP), ferritin, white blood cell count (WBCC), and neutrophil count (NC), with changes in adiposity and linear growth in a longitudinal study of school‐age children from Bogotá, Colombia.MethodsWe quantified CRP, ferritin, WBCC, and NC from samples collected among 2708 children aged 5–12 y at baseline. Anthropometric characteristics were measured periodically for a median of 30 months. We estimated mean change in age‐ and sex‐standardized BMI‐ and height‐for‐age Z‐scores and waist circumference according to quartiles of each inflammatory marker at baseline using multivariable mixed effects linear regression models.ResultsThere were no associations between any of the subclinical inflammation biomarkers and change in indicators of adiposity over follow‐up. However, ferritin serostatus was inversely related to linear growth after adjustment for CRP, an independent indicator of inflammation, and potential confounders. Compared to children in the lowest quartile of ferritin, those in the highest quartile had an annual change in height‐for‐age that was 0.03 Z lower (P trend=0.001).ConclusionCRP, ferritin, WBCC, and NC do not predict weight gain in school‐age children. However, high iron status, indicated by CRP‐adjusted ferritin concentrations, may be related to slower linear growth.Grant Funding Source : University of Michigan Center for Global Health

Abstract P117: Elevated Liver Transaminases are Associated with an Increased Risk of Atrial Fibrillation

Background: For the management of an initial episode of atrial fibrillation (AF), guidelines recommend assessment of liver function tests; nonetheless, the rationale and supporting evidence for the recommendation remain unclear. We tested the hypothesis that elevated liver transaminases, assessed by alanine transaminase (ALT) and aspartate transaminase (AST) are associated with the incidence of AF in a community-based cohort. Methods and Results: From the Framingham Heart Study Original and Offspring cohorts we investigated 3779 participants (mean age 65±10 years, 56.8% females). After up to 10 years of follow-up (29,099 person years), 383 individuals developed AF. We used Cox proportional hazards models to assess the association between liver transaminases and AF incidence, and adjusted the model for established AF risk factors and alcohol consumption. Both ALT and AST showed significant association with incident AF (Table). When we excluded participants with moderate / severe alcohol consumption, the associations for ALT and AST remained consistent (Table). Additional adjustment for C-reactive protein (inflammatory marker) only mildly lowered the effect estimates for both transaminases, but decreased the level of significance (Table). We additionally estimated the ability of transaminasess to predict AF risk. When assessed by the continuous net reclassification improvement, both ALT and AST marginally improved AF risk prediction [ALT: 0.18 (95% confidence interval, 0.07-0.29; p=0.002); AST: 0.16 (95% confidence interval, 0.04-0.28; p=0.003)]. Conclusions: Higher mean levels of ALT and AST, are associated with the incidence of AF, even when adjusted for various established AF risk factors. However, transaminases contribute only subtly towards an improvement in AF risk prediction. Pathophysiologic mechanisms explaining the association are uncertain and merit further investigation.

Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory mediator involved in atherosclerosis. Since aortic valve stenosis (AVS) is regarded as an atherosclerosis-like inflammatory disease, we sought to investigate whether AVS is associated with elevated Lp-PLA2. Plasma Lp-PLA2 levels were determined in 48 consecutive patients with severe AVS without atherosclerotic vascular disease and compared with the values obtained in 48 controls matched for age, sex and cardiovascular risk factors. Lp-PLA2 was higher in AVS than in controls (242.3±50.4 vs. 151.9±28.1 ng/mL, p<0.0001). Lp-PLA2 correlated inversely with aortic valve area (AVA) (r=-0.53; p=0.0001) and positively with mean pressure gradient (PG) (r=0.32; p=0.029). In multivariable analysis C-reactive protein (CRP) (OR=1.42; 95% CI 0.95-2.1; p=0.09) and AVA (OR=0.003; 95% CI 0.00004-0.23; p<0.01) were independently associated with Lp-PLA2 above a mean of 242 ng/mL. After adjustment for CRP, AVA was the only independent predictor of Lp-PLA2 in AVS patients (p<0.001). This study is the first to show that AVS is characterized by increased plasma Lp-PLA2 levels associated with the severity of AVS, which suggests active involvement of Lp-PLA2 in the pathogenesis of AVS.

Plasma resistin, adiponectin, and risk of incident atrial fibrillation: The Framingham Offspring Study

We sought to investigate whether higher concentrations of resistin and lower concentrations of adiponectin relate to incident atrial fibrillation (AF) and whether this association is mediated by AF risk factors and inflammation. Resistin and adiponectin are adipokines that have been associated with multiple known risk factors for AF including diabetes, obesity, inflammation, and heart failure. We studied the relations between circulating concentrations of both adipokines and incident AF in participants of the Framingham Offspring Study. Participants (n = 2,487) had a mean age of 61 ± 10 years, and 54% were women. During a mean follow-up of 7.6 ± 2.0 years, 206 (8.3%) individuals (96 women) developed incident AF. Plasma resistin concentration was significantly associated with incident AF (multivariable-adjusted hazard ratio [HR] 1.17 per SD [0.41 ng/mL] of natural logarithmically transformed resistin, 95% CI 1.02-1.34, P = .028). The resistin-AF association was attenuated after further adjustment for C-reactive protein (HR per SD increase resistin 1.14, 95% CI 0.99-1.31, P = .073). Adiponectin concentrations were not significantly associated with incident AF (multivariable-adjusted HR of 0.95 per SD [0.62 μg/mL] of logarithmically transformed adiponectin, 95% CI 0.81-1.10, P = .478). In our community-based longitudinal study, higher mean concentrations of resistin were associated with incident AF, but the relation was attenuated by adjustment for C-reactive protein. We did not detect a statistically significant association between adiponectin and incident AF. Additional studies are needed to clarify the potential role of adipokines in AF and mechanisms linking adiposity to AF.

Effect of Serum 25-Hydroxyvitamin D on Risk for Type 2 Diabetes May Be Partially Mediated by Subclinical Inflammation

OBJECTIVETo assess the association between serum 25-hydroxyvitamin D (25-OHD) and incident type 2 diabetes and to determine whether the association is mediated by subclinical inflammation.RESEARCH DESIGN AND METHODSUsing a case-cohort design, baseline levels of 25-OHD were measured in 416 case subjects with incident type 2 diabetes and 1,267 noncase subjects selected from a source population of 7,936 middle-aged participants in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) study.RESULTSA significant inverse association was observed between serum 25-OHD and incident type 2 diabetes after adjustment for diabetes risk factors and season. The hazard ratio (HR) and 95% CI comparing tertile extremes was 0.63 (0.44–0.90) (Ptrend = 0.010). Further adjustment for C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, and interferon-γ–inducible protein-10 attenuated this association by 16% (HR 0.73 [0.50–1.05], P = 0.090).CONCLUSIONSVitamin D status is inversely related to type 2 diabetes risk and our data suggest that this association may be partially mediated by subclinical inflammation.

Soluble P-Selectin Levels Are Associated with Cardiovascular Mortality and Sudden Cardiac Death in Male Dialysis Patients

Background/Aims: P-selectin is released by activated platelets and endothelium contributing to inflammation and thrombosis. We evaluated the association between soluble P-selectin and atherosclerotic cardiovascular disease (ASCVD) in dialysis patients. Methods: We measured soluble P-selectin in serum from 824 incident dialysis patients. Using Cox proportional hazards models, we modeled the association of P-selectin levels with ASCVD events, cardiovascular mortality and sudden cardiac death. Results: After adjustment for demographics, comorbidity and traditional cardiovascular risk factors, higher P-selectin levels were associated with increased risk of ASCVD and cardiovascular mortality among males (p = 0.02 and p = 0.01, respectively), but not females (p = 0.52 and p = 0.31, respectively; p interaction = 0.003), over a median of 38.2 months. Higher P-selectin was associated with a greater risk of sudden cardiac death among males (p = 0.05). The associations between increasing P-selectin and cardiovascular mortality as well as sudden cardiac death in males persisted after adjustment for C-reactive protein, interleukin-6, serum albumin and platelet count (p = 0.01 and p = 0.03, respectively). The risk for sudden cardiac death was more than 3 times greater for males in the highest tertile of soluble P-selectin compared with the lowest tertile after adjustment (HR: 3.19; 95% CI: 1.18 – 8.62; p = 0.02). Conclusion: P-selectin is associated with ASCVD, cardiovascular mortality and sudden cardiac death among male dialysis patients.

Association of Serum Procalcitonin With Cardiovascular Prognosis in Coronary Artery Disease

Procalcitonin (PCT) is an established biomarker for the diagnosis of sepsis. Evidence is growing that PCT concentration correlates with the extent of atherosclerosis and prognosis in patients with coronary artery disease (CAD). A total of 2,131 patients with CAD were followed up for a median of 3.6 years. During follow-up, death from cardiovascular causes was registered in 95 patients and non-fatal myocardial infarction in 85 patients. Median and quartile 1 and 3 are reported for PCT concentration. Patients who died of cardiovascular causes had higher PCT concentrations [0.021 (0.012/0.036) ng/ml vs. 0.015 (0.010/0.023) ng/ml; P<0.0001]. Patients with acute coronary syndrome had increased concentrations of PCT in relation to patients with stable angina [0.016 (0.011/0.027) ng/ml vs. 0.014 (0.009/0.014) ng/ml; P for trend <0.0001]. PCT concentration across quartiles was associated with the event rate (P=0.026; log-rank test) and mortality (P=0.00018). On Cox regression analysis, elevated PCT concentration was related to cardiovascular mortality [hazard ratio (HR), 1.34; 95% confidence interval (CI): 1.08-1.65, P=0.0070], but not to cardiovascular events (HR, 1.09; 95%CI: 0.93-1.28, P=0.28). After adjustment for C-reactive protein (CRP), PCT did not provide additional prognostic information. PCT is associated with future cardiovascular mortality in patients with CAD, but PCT is not superior to CRP for prediction of outcome.

Resistin, exercise capacity, and inducible ischemia in patients with stable coronary heart disease: Data from the Heart and Soul study

Objective Resistin is an adipocytokine involved in insulin resistance, inflammation, and atherosclerosis. Its role in the development and progression of coronary heart disease (CHD) is not yet well-characterized. We performed a cross-sectional study to evaluate the association between serum resistin levels, exercise capacity, and exercise-induced cardiac ischemia among patients with stable CHD. Methods and results We measured serum resistin concentrations and determined treadmill exercise capacity and inducible ischemia by stress echocardiography in 899 outpatients with documented CHD. Of these, 215 (24%) had poor exercise capacity (<5 metabolic equivalent tasks), and 217 (24%) had inducible ischemia. As compared with participants who had resistin levels in the lowest quartile, those with resistin levels in the highest quartile were more likely to have poor exercise capacity (33% versus 16%, odds ratio [OR] 2.68, P < 0.0001) and inducible ischemia (30% versus 17%, OR 2.08, P = 0.001). Both associations remained robust after adjusting for numerous clinical risk factors, metabolic variables, and markers of insulin resistance (poor exercise capacity adjusted OR 1.73, P = 0.04; inducible ischemia adjusted OR 1.82, P = 0.01). However, further adjustments for C-reactive protein, interleukin-6, and tumor necrosis factor-α eliminated the association with poor exercise capacity (adjusted OR 1.50, P = 0.14) and substantially weakened the association with inducible ischemia (adjusted OR 1.72, P = 0.03). Conclusions Elevated serum resistin is associated with poor exercise capacity and exercise-induced cardiac ischemia in patients with stable coronary disease. Adjustment for inflammatory markers attenuated these associations, suggesting a possible role for resistin in inflammation and CHD pathophysiology.

Low Serum Levels of Dehydroepiandrosterone Sulfate Predict All-Cause and Cardiovascular Mortality in Elderly Swedish Men

The age-related decline in dehydroepiandrosterone (DHEA) levels is thought to be of importance for general and vascular aging. However, data on the association between DHEA and mortality are conflicting. We tested the hypothesis that low serum DHEA and DHEA sulfate (DHEA-S) levels predict all-cause and cardiovascular disease (CVD) death in elderly men. We used gas/liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based MrOS Sweden study (2644 men, aged 69-81 yr). Mortality data were obtained from central registers and analyzed using Cox proportional hazards regressions. All-cause and CVD mortality by serum DHEA(-S) levels. During a mean 4.5-yr follow-up, 328 deaths occurred. Low levels of DHEA-S (quartile 1 vs. quartiles 2-4), predicted death from all causes [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.21-1.96; adjusted for traditional cardiovascular risk factors], from CVD (n = 123 deaths; HR 1.61, 95% CI 1.10-2.37) and ischemic heart disease (n = 73; HR 1.67, 95% CI 1.02-2.74) but not cancer. Analyses with DHEA gave similar results. The association between low DHEA-S and CVD death remained after adjustment for C-reactive protein and circulating estradiol and testosterone levels. When stratified by the median age of 75.4 yr, the mortality prediction by low DHEA-S was more pronounced among younger (age adjusted HR for CVD death 2.64, 95% CI 1.37-5.09) than older men (HR 1.30, 95% CI 0.83-2.04). Low serum levels of DHEA(-S) predict death from all causes, CVD, and ischemic heart disease in older men.

Cigarette smoking and serum liver enzymes: the role of alcohol and inflammation

Smoking may affect the liver through inflammatory pathways and may aggravate the pathogenic effects of alcohol on the liver. We have examined the relationship between cigarette smoking and liver enzymes and the role of alcohol and C-reactive protein (CRP), a marker of inflammation. The subjects consisted of 4595 men aged 40-59 y with no history of coronary heart disease drawn from general practices in 24 British towns. Cigarette smoking was significantly associated with increased levels of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) (P < 0.0001) and was inversely associated with increased aspartate aminotransferase (AST) after adjustment for alcohol intake, body mass index and physical activity. Compared with never smokers, heavy cigarette smokers (> or =40/day) were associated with increased odds of elevated GGT (> or =23 IU/L) (adjusted odds ratio [OR] 1.56 [1.08, 2.27]), which was abolished after adjustment for CRP (adjusted OR 1.27 [0.87, 1.86]). There was a significant interaction between smoking and alcohol on GGT. In the absence of heavy drinking, there was no association between smoking and GGT after adjustment for CRP. Among heavy drinkers, smoking was associated with increased levels of GGT independent of CRP. Smoking was associated with increased odds of elevated ALP (> or =11 IU/L) (adjusted OR 3.95 [2.77, 5.62]), which persisted after adjustment for CRP and white cell count (adjusted OR 2.90 [1.99-4.23]), possibly reflecting increased bone cell activity. The findings suggest that cigarette smoking does not cause liver injury, but may enhance the effects of alcohol on liver cell injury in heavy drinkers.

Comparison of two malnutrition risk screening methods (MNA and NRS 2002) and their association with markers of protein malnutrition in geriatric hospitalized patients

Malnutrition occurs frequently in the elderly and is associated with increased morbidity and mortality. The mini-nutritional assessment (MNA) has been used most frequently in the geriatric literature. The nutritional risk screening 2002 (NRS) has been proposed as universal screening method for hospitalized patients. The aim of our study was to compare both tools as they are correlated with protein malnutrition. MNA, NRS, and markers of protein malnutrition were measured in 104 consecutive inpatients admitted to an acute geriatric ward. The median age was 84 years (IQR: 78-89), 81 were females. The median body mass index was 23.1 kg/m(2) (IQR: 20-27.3), the median upper-arm and calf circumferences were 25 cm (IQR: 23-29) and 33 cm (IQR: 29-36). According to MNA, 23 patients were malnourished, 50 at risk of malnutrition, and 31 had a normal nutritional status. The NRS indicated that 35 were at moderate to severe risk of malnutrition and 69 at low risk. Serum prealbumin and retinol-binding protein concentrations were inversely associated with the severity of malnutrition as indicated by the NRS (P=0.06 and <0.01, respectively), whereas the MNA was not associated with these serum proteins. After adjustment for C-reactive protein and creatinine clearance, only retinol-binding protein concentrations were consistently associated with both malnutrition scores. The NRS seems to be superior compared with the MNA and serum proteins in identifying elderly patients at risk of malnutrition during acute intercurrent illness.

“Atherogenic index of plasma” (log10 triglyceride/high-density lipoprotein−cholesterol) predicts high blood pressure, diabetes, and vascular events

To determine the association of atherogenic index of plasma (AIP), the logarithm of molar ratio of triglyceridemia to high-density lipoprotein cholesterol (TG/HDL-cholesterol) with cardiometabolic disorders was investigated in a sample of the Turkish population. A total of 2676 middle-aged adults were prospectively evaluated with a clinical examination and laboratory tests during 7.8 years' follow-up. AIP was significantly associated in multiple linear regression analyses with greater apolipoprotein B and lower low-density lipoprotein (LDL)-cholesterol levels, reflecting the presence of smaller LDL particle size. Whereas in men insulin levels, obesity, and nonHDL-cholesterol were major determinants, C-reactive protein (CRP) was the strongest determinant of AIP among women, independent of body mass index. Top quartiles of AIP predicted significantly age-adjusted incident coronary heart disease (CHD) in both sexes, more strongly in women, in whom quartile 3 also was a predictor with a greater than 2-fold relative risk. Associations remained significant after adjustment for CRP and traditional risk factors. AIP significantly predicted diabetes and high blood pressure in both sexes after adjustment for age and CRP. With regard to incident high blood pressure, the risk ratio in men was attenuated when body mass index also was adjusted. High AIP, a surrogate of small LDL particle size, reflects obesity and hyperinsulinemia in men and high CRP status in women. It predicts CHD independently, type 2 diabetes mediated by obesity in men and in women, high blood pressure, metabolic syndrome, and CHD potentially mediated by involvement in a proinflammatory status reflected by CRP.

Lipoprotein-Associated Phospholipase A 2 and Risk of Congestive Heart Failure in Older Adults

Background— Inflammation may be a causative factor in congestive heart failure (CHF). Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is an inflammation marker associated with vascular risk. One previous study showed an association of Lp-PLA 2 activity with CHF risk, but there were only 94 CHF cases and Lp-PLA 2 antigen, which is available clinically in the United States, was not measured. Methods and Results— We measured baseline Lp-PLA 2 antigen and activity in 3991 men and women without baseline CHF or cardiovascular disease who were participating in the Cardiovascular Health Study, a prospective observational study of adults 65 years or older. Cox proportional hazards models adjusted for age, sex, clinic site, race, low-density and high-density lipoprotein cholesterol, body mass index, systolic and diastolic blood pressure, hypertension, smoking status, pack-years, and diabetes were used to calculate hazard ratios and 95% CIs for incident CHF. Further models adjusted for coronary disease events during follow-up and C-reactive protein. Eight hundred twenty-nine participants developed CHF during 12.1 years. Adjusted hazard ratios for CHF with Lp-PLA 2 in the fourth compared with the first quartile were 1.44 (95% CI, 1.16 to 1.79) for Lp-PLA 2 antigen and 1.06 (95% CI, 0.84 to 1.32) for activity. Adjustment for incident coronary disease attenuated the hazard ratio for Lp-PLA 2 antigen to 1.26 (95% CI, 1.02 to 1.57), adjustment for C-reactive protein had minimal impact. Conclusions— Lp-PLA 2 antigen was associated with risk of future CHF in older people, independent of CHF and coronary risk factors, and partly mediated by coronary disease events. Further clinical and basic research is needed to better understand the role of Lp-PLA 2 in CHF.

Relationship between serum progesterone concentrations and cardiovascular disease, diabetes, and mortality in elderly Swedish men and women: An 8-Year prospective study

The use of synthetic progesterone-like substances in hormone replacement therapy and birth control pills has been associated with increases in cardiovascular morbidity and the prevalence of diabetes. The primary aims of this study were to investigate whether physiologic concentrations of progesterone might also be associated with cardiovascular disease and diabetes, and to explore potential gender differences in these associations in elderly Swedish men and women. This prospective, longitudinal study was performed in a Swedish population-based sample of opposite-sex twins aged between 71 and 80 years who were not receiving sex hormone therapy. Serum concentrations of progesterone, estradiol, C-reactive protein (CRP), and urea were measured at baseline (1996) and at 8-year follow-up (2004), and serum concentrations of cystatin and insulin were measured only at follow-up. The outcomes of interest were cardiovascular morbidity (myocardial infarction, angina pectoris, peripheral arterial disease, stroke, congestive heart failure [CHF], cardiac arrhythmia, hypertension, and thromboembolism), diabetes, and mortality throughout the observation period. At baseline, the study sample included 230 men and 195 women (mean [SD] age, 74.6 [2.6] years). At follow-up, 132 men and 145 women (mean age, 82.4 [2.5] years) met the inclusion criteria, of whom 128 men and 112 women did so at both baseline and follow-up. Serum progesterone concentrations, which did not differ significantly from reported concentrations for the age group, were significantly associated with mortality across the observation period (P < 0.001). At follow-up, higher serum progesterone was significantly associated with the occurrence of CHF (P < 0.01); this association remained robust after adjustment for CRP, cystatin, and insulin levels. In these elderly Swedish men and women, increased physiologic concentrations of progesterone were found to be associated with an increased prevalence of CHF, independent of inflammatory factors, markers of renal function, and insulin metabolism.

Vitamin A deficiency and other factors associated with severe tuberculosis in Timor and Rote Islands, East Nusa Tenggara Province, Indonesia

Plasma zinc and vitamin A concentrations have been reported to be low in tuberculosis (TB) patients in some studies, although it is not clear whether this constitutes a risk for a more severe clinical presentation among TB patients. The acute phase reaction may also deplete zinc and vitamin A in the plasma. Therefore, we further studied these associations. We carried out a cross-sectional study among newly diagnosed sputum smear-positive TB patients in East Nusa Tenggara. The patients were categorized as either mild TB when Karnofsky Score (KS) > or =80 or severe TB (KS <80). Body mass index (BMI), mid upper arm circumference (MUAC), chest radiograph, and the results of hemoglobin, erythrocyte sedimentation rate, albumin, C-reactive protein (CRP), zinc and vitamin A in plasma were correlated with TB category. A total of 300 TB patients participated in the study (63% male and 37% female), and were categorized as mild TB (53%) or severe TB (47%). Vitamin A, hemoglobin and plasma albumin were significantly lower, and CRP was significantly higher, in severe TB than in mild TB, and the active lesion area on the chest radiograph was greater among severe TB patients. In a multiple regression analysis, after adjustment for CRP, low vitamin A (beta=3.2, 95%CI (confidence interval) 1.6-4.9, P=0.000) but not zinc, correlated with the severity of TB. MUAC was better than BMI as a predictor of TB severity (beta=1.3, 95%CI 0.6-6.2, P=0.000). Severe TB was associated with vitamin A deficiency. MUAC can be applied as a measure of TB severity.

Red Meat Intake Is Associated with Metabolic Syndrome and the Plasma C-Reactive Protein Concentration in Women

Although red meat consumption has been related to the prevalence of diabetes, few data are available showing the relation among red meat intake, inflammation, and metabolic syndrome. We aimed to identify the association between red meat intake, metabolic syndrome, and circulating concentrations of C-reactive protein (CRP) as a surrogate measure of inflammation. In a cross-sectional study of 482 Tehrani female teachers aged 40-60 y, we used a FFQ to assess red meat intake. Anthropometric measures, blood pressure, fasting plasma glucose, lipid profiles, and plasma CRP concentrations were evaluated according to standard methods. Metabolic syndrome was defined as recommended by National Cholesterol Education Program Adult Treatment Panel III guidelines. Red meat intake (mean +/- SEM) was 45.9 +/- 3.0 g/d. After statistically controlling for potential confounders, geometric mean plasma CRP concentrations across increasing quintile categories of red meat intake were 1.46, 1.66, 1.73, 1.89 +/- 1.89, and 2.03 mg/L (P-trend < 0.01). In the crude model, individuals in the top quintile of red meat intake had greater odds of having metabolic syndrome compared with those in the bottom quintile [odds ratio (OR): 2.33; 95% CI: 1.24, 4.38, P-trend < 0.01]. This association remained significant even after adjustment for potential confounders (OR, 2.15; CI, 1.18, 4.01; P-trend <0.01). Adjustment for CRP did not affect this association (OR, 2.06; CI, 1.16, 3.98; P-trend <0.01). In conclusion, increased red meat consumption is cross-sectionally associated with greater risk of metabolic syndrome and inflammation. Further prospective investigations will be needed to confirm this finding.

Circulating TNFα levels in older men and women do not show independent prospective relations with MI or stroke

BackgroundTumour necrosis factor alpha (TNFα) is a pro-inflammatory cytokine implicated in atherosclerotic plaque formation. We investigated whether circulating TNFα is prospectively associated with myocardial infarction (MI) or stroke in the older general population, independently of established cardiovascular risk factors and other inflammatory markers related to CHD risk. MethodsWe measured baseline TNFα concentrations in stored serum samples of 362 incident MI and 299 incident stroke cases and controls (2 per case, frequency matched by age, gender and town) who were ‘nested’ in parallel prospective studies of 4252 men and 4286 women aged 60–79 years assessed in general practices in 24 British towns in 1998–2000 and followed up for an average 7 years for fatal and non-fatal MI and stroke. ResultsTNFα levels were 11.4% (95% CI 9.5, 13.3%) higher among MI cases than controls; geometric mean 1.84pg/mL compared to 1.63pg/mL, p (difference)<0.001. Participants in the top third of baseline TNFα levels had an age-adjusted odds ratio (OR) for MI of 1.75 (95%CI 1.22, 2.49) compared with those in the bottom third, which was reduced to 1.47 (95%CI 1.01, 2.14) after adjustment for established cardiovascular risk factors. However, further adjustment for C-reactive protein and interleukin-6 abolished the association OR 1.33 (95% CI 0.91, 1.66) and the linear trend. Excluding subjects with pre-existing CVD did not materially affect results. No significant association between TNFα and stroke was observed. ConclusionsThis study suggests that TNFα is not a strong independent risk marker for MI, and is not associated with risk of stroke.