Categories Of hs-CRP Research Articles

Food insecurity, inflammation, and immune function among older US adults: Findings from the health and Retirement study

BackgroundFood insecurity (FI) is a pressing public health concern among older adults and has been associated with adverse cardiovascular outcomes. Greater systemic inflammation may provide a pathway to explain these associations, but few studies have examined the link between FI and markers of inflammation. Thus, the objective of the present study was to evaluate the associations between FI and multiple inflammatory and immune functioning biomarkers using a nationally representative study of US adults aged > 50 years. MethodParticipants (n = 3,924) were drawn from the longitudinal Health and Retirement Study (HRS). Household FI was assessed using the six-item Short Form Food Security Survey Module from the 2013 HRS Health Care and Nutrition Study. Markers of inflammation (neutrophil–lymphocyte ratio, albumin, hs-CRP, IL6, IL10, IL-1Ra, sTNFR-1, and TGFβ-1) and immune functioning (CMV) were collected during the 2016 HRS Venous Blood Study. Multivariate logistic and linear regression models were used to evaluate associations between household FI and inflammatory and immune functioning biomarkers, adjusting for individual and household sociodemographic characteristics. ResultsThe weighted prevalence of FI was 18.8 %. Age and sex-adjusted mean showed that FI was associated with higher levels of inflammation and impaired immune functioning (Ps-value < 0.05). Older adults with FI had higher mean levels of albumin, hs-CRP, IL6, IL10, IL-1Ra, TGFß-1, and CMV seronegative and borderline (Ps-value < 0.05). Multivariate-adjusted regression model showed that FI was associated with high-risk categories of hs-CRP (OR 1.34, 95 % CI 1.06, 1.68), IL-6 (OR 1.66, 95 % CI 1.28, 2.14), IL-1Ra (OR 0.67, 95 % CI 0.48, 0.93), TGFß-1 (OR 1.87, 95 % CI 1.45, 2.42), seronegativity for CMV (OR 0.48, 95 % CI 0.35, 0.64). ConclusionIn this nationally representative sample of older adults, FI was positively associated with multiple markers of systemic inflammation and impaired immune functioning. Public health efforts that directly work to reduce FI among older adults are warranted and may result in further improvements in their health and well-being.

Abstract 16779: Tirzepatide Reduces High-Sensitivity C-reactive Protein in Patients With Type 2 Diabetes and High Cardiovascular Risk: A Post Hoc Analysis of the SURPASS-4 Trial

Background: People with type 2 diabetes (T2D) who have elevated levels of high-sensitivity C-reactive protein (hsCRP) face a greater risk of myocardial infarction and coronary death. Early data for tirzepatide (TZP), a GIP/GLP-1 receptor agonist, suggest a hsCRP lowering effect. Here, we compare the effect of TZP and insulin glargine (iGlar) on hsCRP in patients with T2D and established or high risk for cardiovascular (CV) disease. Methods: hsCRP concentration was quantified by immunoassay (Roche, Indianapolis, IN) with lower limits of detection at concentrations of 0.15 mg/L. Plasma was collected from 1995 fasted participants at baseline (329, 328, 338, and 1000 on 5, 10, 15 mg TZP and on iGlar, respectively) and 52 weeks in SURPASS-4. The % changes of hsCRP from baseline were estimated by mixed model with repeated measures. The shifts in hsCRP risk categories (hsCRP &gt;3 mg/L or 1-3 mg/L versus &lt;1 mg/L) from baseline to 52 weeks are reported. The linear relationship between % change from baseline of hsCRP and change in body mass index (BMI) was analyzed using Pearson correlation coefficient. Results: Baseline hsCRP (mean ± SD, 5.6 ± 12.5 mg/L) was elevated in this study population. Among the participants, 48%, 36%, and 16% were in the &gt;3, 1-3 and &lt;1 mg/L hsCRP categories, respectively. Participants in the elevated hsCRP categories had higher body weight and BMI at baseline. After 52 weeks of treatment, the 5, 10, 15 mg TZP and iGlar groups resulted in -38.0%, -44.2%, -47.8%, and 0.6% changes in the concentration of hsCRP, respectively. More TZP-treated patients improved their hsCRP categories when compared with iGlar-treated participants (Table). The reduction in hsCRP in the pooled TZP groups correlated with the reduction of BMI (r=0.07, p=0.049). Conclusions: Tirzepatide treatment significantly lowers hsCRP in patients with T2D and increased CV risk versus baseline and iGlar. Substantially more participants shift to a lower hsCRP category when compared with insulin glargine.

Asupan vitamin A, vitamin C, vitamin E, BCAA dan kaitannya dengan kadar hs-CRP pada member fitness center dewasa

Excessive physical exercise can stimulate proinflammatory cytokines expressions and increases high sensitivity C-Reactive Protein (hs-CRP). Branched Chain Amino Acids (BCAA) and vitamins A, C, and E are antioxidant mechanisms to reduce oxidative stress. This study analyzes the correlation between vitamin A, C, E, and BCAA intake with hs-CRP. The study design was cross-sectional, which was conducted in Semarang. Participants were 48 men aged 20-43 years. Sampling used consecutive sampling. Data were collected using food recall 3x24h to assess dietary intake and laboratory tests using the Immunoturbidimetric method to determine hs-CRP levels. Data were statistically analyzed using Spearman-Rank and multiple linear regression. The result showed that the subject with high-risk categories of hs-CRP was 18,8%. The intake of BCAA was 10,8% from supplements. Most subjects had an excessive intake of vitamin A but did not meet the needs of vitamins C and E. There was no correlation between BCAA intake (p= 0,681) and vitamin C intake (p= 0,137) with hs-CRP levels. However, there was a negative correlation between vitamin A (p= 0,003) and vitamin E (p= 0,013) intake with hs-CRP levels. Multivariate analysis showed that the intake of vitamin A associated with hs-CRP levels of 8,1% (p= 0,028). In conclusion, vitamin A intake is the most influential factor in hs-CRP levels in fitness center members.

Abstract 11263: Multiple Inflammation Biomarkers and Incident Coronary Heart Disease Risk Among Black and White US Adults: The REGARDS Study

Introduction: Inflammation biomarkers have been individually associated with increased risk of coronary heart disease (CHD). However, little is known of the association between multiple inflammation biomarker counts in the high-risk category and incident CHD risk. Methods: We used data from the REasons for Geographic and Racial Differences in Stroke study, an ongoing national cohort of 30,239 Black and White US adults aged ≥45 years recruited in 2003-2007. Baseline levels of C-reactive protein (hsCRP), white blood cell count (WBC) and serum albumin were divided into tertiles. High-risk categories of hsCRP and WBC were defined as levels above the 3 rd tertile (3.75 mg/dL and 6.31 x 10 9 cells/L, respectively) and albumin levels below the 1 st tertile (4.0 g/dL). Four mutually exclusive groups were derived corresponding to having 0, 1, 2 or 3 biomarkers in the high-risk category. Outcome was a composite of incident non-fatal myocardial infarction and fatal CHD. Results: Of 15,738 participants free of CHD at baseline (mean age 63.1 years, 65.3% female, 40.8% black), 38.9% (n = 6,121) had 0, 36.6% (n = 5,765) had 1, 19.7% (n = 3,107) had 2, 4.7% (n = 745) had 3 inflammation biomarkers in the elevated levels. With median follow-up of 10.5 years, 902 (5.7%) participants had incident CHD. The rates of incident CHD and 95% confidence intervals (CI) per 1000 person years increased progressively for individuals with 0, 1, 2, and 3 inflammation biomarkers in the high-risk category: 4.4 (95% CI: 3.9-5.0), 6.3 (95% CI: 5.7-7.0), 8.9 (95% CI: 7.8-10.0), and 10.3 (95% CI: 7.7-12.8), respectively. The fully adjusted hazard ratios (95% CI) for incident CHD associated with 1, 2 and 3 versus no inflammation biomarker in the high-risk category were 1.28 (1.08-1.51), 1.71 (1.42-2.06), and 1.90 (1.43-2.54), respectively (P trend &lt; 0.001) (Table). Conclusions: The count of inflammation biomarkers in the high-risk category is associated with increased risk of CHD independent of traditional risk factors.

Association between a metabolic syndrome score and high sensitivity C-reactive protein in European children: the IDEFICS study

AbstractIntroductionMetabolic syndrome (MetS) is a combination of risk factors that may be present already in childhood. MetS has been associated with inflammatory biomarkers such as high sensitivity C-reactive protein (hsCRP) in aduls. In 2014, Ahrens et al, published reference standards for a paediatric MetS score based on reference values from European children. The aim of this study is to assess longitudinally the relationship between a MetS score and hsCRP in a sample of European children.Materials and MethodsOut of the baseline sample of the IDEFICS Study, 2913 children aged 2–9 years were included in this study. Inclusion criteria was having available data of waist circumference (WC), diastolic and systolic blood pressure (DBP, SBP), high density lipoprotein (HDL) cholesterol, triglycerides (TG), glucose and insulin, to calculate the homeostasis model assessment index (HOMA); and hs-CRP as a marker of inflammation, at baseline (T0) and two years later (T1). hs-CRP was categorized into two categories as some children had lower concentration than the detection limit of 0.02mg/dL. Student t-test and logistic regression were used to assess these associations. Logistic regression was adjusted by age, sex, body mass index (BMI), socioeconomic level and country.ResultsDifferences of mean values of the components of the MetS and the two categories of hs-CRP were observed between both time points. Mean values of SBP, DBP, WC, TG and HOMA were significantly higher in children with a higher category of hsCRP (p &lt; 0.005). In addition, MetS score was significantly higher in those with a higher category of hs-CRP (p &lt; 0.001) at both measurement points, T0 and T1. Finally, logistic regression between components of MetS and categories of hs-CRP, at both time points, showed significant associations (p &lt; 0.001) for WC (OR = 1.06 at T0 and OR = 1.04 at T1) and HDL (OR = 0.98 at T0 and OR = 0.98 at T1) and the MetS score (OR = 1.07) score at T1.DiscussionThe association between MetS and inflammation is already present in children. Out of the components of the MetS, WC and HDL were the ones more associated with an inflammatory state at two times points. Also the MetS score, but only at the follow-up, was associated with the hs-CRP. Therefore, in order to prevent the inflammatory state in childhood, efforts to improve the metabolic profile, specially WC and HDL, need to be made.

Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease

BackgroundThere is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is associated with CAD, and the effects of testosterone on CAD as reported in literature have been considered as anti-atherosclerotic. The present study aimed to examine the possible association between serum GDF-15 and testosterone in male CAD patients.MethodsGDF-15 and testosterone concentrations were determined in blood samples of 426 male patients with CAD and 220 male controls. Serum concentrations of hs-CRP, and other baseline characteristics were also measured.ResultsSerum levels of GDF-15 were higher in CAD patients when compared to controls, and testosterone concentrations were lower (p < 0.001). Patients with low testosterone levels had higher concentrations of GDF-15 (p < 0.001). In stratified analyses, inverse relations between GDF-15 levels and testosterone were noted for almost all strata, stratified by categories of hs-CRP, leukocytes, neutrophils, neutrophil to lymphocyte ratio, glucose, HDL-c, and LDL-c, and whether had hypertension, diabetes, and underwent percutaneous coronary intervention (PCI). Furthermore, in the linear regression models with bootstrap resampling with 1000 replications, high GDF-15 levels were independently associated with testosterone deficiency in male patients with CAD.ConclusionsIn male patients with CAD, high GDF-15 levels were associated with testosterone deficiency. These results support that upregulation of GDF-15 in the presence of low testosterone levels during CAD progression is a potential mechanism by which GDF-15 affects CAD.

Associations between very low concentrations of low density lipoprotein cholesterol, high sensitivity C-reactive protein, and health outcomes in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study.

Recent findings have demonstrated the important contribution of inflammation to the risk of cardiovascular disease (CVD) in individuals with optimally managed low density lipoprotein cholesterol (LDL-C). We explored relationships between LDL-C, high sensitivity C-reactive protein (hs-CRP), and clinical outcomes in a free-living US population. We used data from the REasons for Geographical And Racial Differences in Stroke (REGARDS), and selected individuals at 'high risk' for coronary events with a Framingham Coronary Risk Score of ≥10% or atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% in order to explore relationships between low LDL-C [<70 mg/dL (1.8 mmol/L) in comparison to ≥70 mg/dL (1.8 mmol/L)]; hs-CRP <2 compared with ≥2 mg/L and clinical outcomes [all-cause mortality, incident coronary heart disease (CHD), and incident stroke]. To assess the association between the LDL-C and hs-CRP categories and each outcome, a series of incremental Cox proportional hazards models were employed on complete cases. To account for missing observations, the most adjusted model was used to interrogate the data using multiple imputation with chained equations (MICE). In this analysis, 6136 REGARDS high-risk participants were included. In the MICE analysis, participants with high LDL-C (≥70 mg/dL) and low hs-CRP (<2 mg/L) had a lower risk of incident stroke [hazard ratio (HR) 0.69, 0.47-0.997], incident CHD (HR 0.71, 0.53-0.95), and CHD death (HR 0.70, 0.50-0.99) than those in the same LDL-C category high hs-CRP (≥2 mg/L). In participants with high hs-CRP (≥2 mg/dL), low LDL-C [<70 mg/dL (1.8 mmol/L)] was not associated with additional risk reduction of any investigated outcome, but with the significant increase of all-cause mortality (HR 1.37, 1.07-1.74). In this high-risk population, we found that low hs-CRP (<2 mg/L) appeared to be associated with reduced risk of incident stroke, incident CHD, and CHD death, whereas low LDL-C (<70 mg/dL) was not associated with protective effects. Thus, our results support other data with respect to the importance of inflammatory processes in the pathogenesis of CVD.

Inflammatory and Cholesterol Risk in the FOURIER Trial.

In the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. It is not known whether the efficacy of evolocumab is modified by baseline inflammatory risk. We explored the efficacy of evolocumab stratified by baseline high-sensitivity C-reactive protein (hsCRP). We also assessed the importance of inflammatory and residual cholesterol risk across the range of on-treatment LDL-C concentrations. Patients (n=27 564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8-2.5). The effects of evolocumab on the primary end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization, and the key secondary end point of cardiovascular death, myocardial infarction, or stroke were compared across strata of baseline hsCRP (<1, 1-3, and >3 mg/dL). Outcomes were also assessed across values for baseline hsCRP and 1-month LDL-C in the entire trial population. Multivariable models adjusted for variables associated with hsCRP and 1-month LDL-C were evaluated. A total of 7981 (29%) patients had a baseline hsCRP<1 mg/L, 11 177 (41%) had a hsCRP 1 to 3 mg/L, and 8337 (30%) had a hsCRP >3 mg/L. Median (interquartile range) baseline hsCRP was 1.8 (0.9-3.6) mg/L and levels were not altered by evolocumab (change at 48 weeks of -0.2 mg/dL [-1.0 to 0.4] in both treatment arms). In the placebo arm, patients in higher baseline hsCRP categories experienced significantly higher 3-year Kaplan-Meier rates of the primary and key secondary end points: 12.0%, 13.7%, and 18.1% for the primary end point (Ptrend<0.0001) and 7.4%, 9.1%, and 13.2% for the key secondary end point (Ptrend<0.0001) for categories of <1, 1 to 3, and >3 mg/dL, respectively. The relative risk reductions for the primary end point and key secondary end point with evolocumab were consistent across hsCRP strata (P-interactions>0.15 for both). In contrast, the absolute risk reductions with evolocumab tended to be greater in patients with higher hsCRP: 1.6%, 1.8%, and 2.6% and 0.8%, 2.0%, and 3.0%, respectively, for the primary and key secondary end points across hsCRP strata. In adjusted analyses of the association between LDL-C and hsCRP levels and cardiovascular risk, both LDL-C and hsCRP were independently associated with the primary outcome (P<0.0001 for each). LDL-C reduction with evolocumab reduces cardiovascular events across hsCRP strata with greater absolute risk reductions in patients with higher-baseline hsCRP. Event rates were lowest in patients with the lowest hsCRP and LDL-C. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.

Usefulness of Lipoprotein-Associated Phospholipase A2 Activity and C-Reactive Protein in Identifying High-Risk Smokers for Atherosclerotic Cardiovascular Disease (from the Atherosclerosis Risk in Communities Study)

Despite the causal role of cigarette smoking in atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms are not fully understood. We evaluated the joint relation between smoking and inflammatory markers with ASCVD risk. We tested cross-sectional associations of self-reported smoking status (never, former, current) and intensity (packs/day) with lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and high-sensitivity C-reactive protein (hsCRP) in 10,506 Atherosclerosis Risk in Communities participants at Visit 4 (1996 to 1998). Using Cox hazard models adjusted for demographic and traditional ASCVD risk factors, we examined the associations of smoking status and intensity with incident adjudicated ASCVD events (n = 1,745 cases) over an average of 17 years, stratified by Lp-PLA2 and hsCRP categories. Greater packs/day smoked was linearly associated with higher levels of both Lp-PLA2 and hsCRP among current smokers. Compared with never smokers, the hazard ratio for incident ASCVD in current smokers was 2.04 (95% CI 1.76 to 2.35). Among current smokers, the risk for ASCVD per 1 pack/day greater was 1.39 (1.10 to 1.76). Both Lp-PLA2 activity ≥253 nmol/min/ml and hsCRP >3 mg/L identified current smokers at the highest risk for incident ASCVD, with similar hazard ratios. hsCRP risk-stratified current smokers better based on intensity. Among current smokers, hsCRP improved ASCVD prediction beyond traditional risk factors better than Lp-PLA2 (C-statistic 0.675 for hsCRP vs 0.668 for Lp-PLA2, p = 0.001). In this large cohort with long follow-up, we found a dose-response relation between smoking intensity with Lp-PLA2 activity, hsCRP, and ASCVD events. Although both Lp-PLA2 activity and hsCRP categories identified high risk among current smokers, hsCRP may better stratify risk of future ASCVD.

P627Associations between very low concentrations of LDL-cholesterol and health outcomes in the reasons for geographical and racial differences in stroke (REGARDS) Study

Introduction: Recent findings have demonstrated the important contribution of inflammation to the risk of cardiovascular disease (CVD) in individuals with optimally managed low density lipoprotein cholesterol (LDL-C). We explored relationships between LDL-C, high sensitivity C-reactive protein (hsCRP) and clinical outcomes in a free-living US population. Methods: We used data from the REasons for Geographical And Racial Differences in Stroke (REGARDS), and selected individuals at “high risk” for coronary events with a Framingham Coronary Risk Score of >10% or atherosclerotic cardiovascular disease (ASCVD) risk >7.5% in order to explore relationships between low LDL-C ( 70 mg/dl [1.8 mmol/L]); hs-CRP <2 compared to ≥2 mg/L and clinical outcomes (all-cause mortality, incident coronary heart disease [CHD] and incident stroke). To assess the association between the LDL-C and hs-CRP categories and each outcome, a series of incremental Cox proportional hazards models were employed on complete cases. To account for missing observations, the most adjusted model was used to interrogate the data using multiple imputation with chained equations (MICE). Results: In this analysis, 6136 REGARDS high risk participants were included. In the MICE analysis, participants with high LDL-C (>70 mg/dl) and low hs-CRP (<2 mg/L) had a lower risk of incident stroke (hazard ratio [HR] 0.69, 0.47-0.997) incident CHD (HR 0.71, 0.53- 0.95) and CHD death (HR 0.70, 0.50-0.99) than those in the same LDL-C category high hs- CRP (≥2 mg/L). In participants with high hsCRP (≥2 mg/dL), low LDL-C (<70 mg/dL [1.8 mmol/L]) was not associated with additional risk reduction of any investigated outcome, but with the significant increase of all-cause mortality (HR 1.37, 1.07-1.74). Conclusions: In this high-risk population, we found that low hsCRP (<2mg/L) appeared to be associated with reduced risk of incident stroke, incident CHD and CHD death, whereas low LDL-C (<70 mg/dL) was not associated with protective effects. Thus, our results support other data with respect to the importance of inflammatory processes in the pathogenesis of CVD.

Abstract 991: Association of high-sensitivity C-reactive protein with health-related quality of life among breast cancer survivors

Abstract Backgrounds/Aims Decline in health-related quality of life (HRQoL) is associated with worse prognosis among patients with breast cancer. Increased risk of inflammation with cancer-related symptoms such as low physical function, depression and pain could be a potential mechanism. We aimed to examine whether high-sensitivity C-reactive protein (hs-CRP) were related to HRQoL among breast cancer survivors. Methods This cross-sectional study of Korean breast cancer survivors included a total of 165 women aged 29 to 63 years who had been diagnosed with stage I to III breast cancer and survived six months or more after surgery. Post-diagnostic HRQoL levels were measured using the 36-Item Short Form Health Survey (SF-36) containing eight components: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotional, and mental health. The higher scores indicated better HRQoL. Circulating levels of hs-CRP were measured using particle-enhanced immunoturbidimetric assay. We categorized hs-CRP levels to four groups; &amp;lt;0.4, 0.4-&amp;lt;0.6, 0.6-&amp;lt;1.0 mg/L (low risk), and ≥1.0 mg/L (average or high risk) on the basis of the Centers for Disease Control/American Heart Association criteria (low risk; &amp;lt;1.0 mg/L, average risk; 1.0-3.0 mg/L, and high risk; &amp;gt;3.0 mg/L). We calculated the least square means (LS-means) and 95% confidence intervals (CIs) using generalized linear models (GLM) to examine the associations of each component with categories of hs-CRP according to HRQoL levels. We adjusted for age at diagnosis, body mass index at diagnosis, weight change, income level, stage at diagnosis, time since surgery, tumor size and plasma vitamin D levels. Results We found that increasing levels of physical functioning and role-physical components were associated with decreasing levels of hs-CRP; according to &amp;lt;0.4, 0.4-&amp;lt;0.6, 0.6-&amp;lt;1.0, and ≥1.0 mg/L of hs-CRP, LS-means (95% CIs) were 78.1 (73.2-83.0), 75.2 (69.6-80.8), 76.1 (69.5-82.7), 70.1 (64.5-75.7), respectively (p for trend = 0.05) for physical functioning and 77.5 (70.6-84.4), 81.0(73.2-88.8), 79.4(70.2-88.7), 66.6(58.7-74.4), respectively (p for trend = 0.05) for role-physical. Higher scores of mental components were also associated with lower levels of hs-CRP; LS-means (95% CIs) of &amp;lt;0.4 and ≥1.0 mg/L of hs-CRP levels were 84.6 (77.8-91.4) and 67.1 (59.4-74.9; p for trend = 0.002) for role-emotional, 87.4 (82.3-92.6) and 77.4 (71.5-83.4; p for trend = 0.03) for social functioning, 62.4 (56.4-68.4) and 53.3 (46.5-60.2; p for trend = 0.05) for vitality. Conclusions High circulating levels of hs-CRP, an inflammation biomarker, were associated with lower levels of HRQoL among Korean breast cancer survivors. Funding information This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT &amp; Future Planning (NRF-2014R1A2A2A01007794) Citation Format: Hyun Jeong Cho, Zisun Kim, Hyun Jo Youn, Jihyoung Cho, Jung Eun Lee. Association of high-sensitivity C-reactive protein with health-related quality of life among breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 991. doi:10.1158/1538-7445.AM2017-991

High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men

We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP) levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD) in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138) of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001). As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range) may require appropriate follow-up and management to prevent NAFLD development.

Abstract P023: Subclinical Inflammation and Weight Change in Middle-aged and Older Adults

Introduction: C-reactive protein (CRP) is a marker of inflammation that is associated with obesity; inflammation also plays a role in the onset of cachexia. CRP and its relationship with weight change (gain and loss) is less well understood, particularly in studies including both middle-aged and older adults. Hypothesis: Elevated CRP is associated with both subsequent body mass index (BMI) gain and even more strongly associated with subsequent BMI loss in middle-aged and older adults. Methods: We analyzed BMI (kg/m2) changes in 11,136 ARIC participants followed since Visit 2 (1990 - 92) when CRP was measured (Table 1). BMI change between study visits was categorized as stable (&lt;+/-2 kg/m2, average of &lt;+/-13 lbs.), gain or loss (&gt;+/-2 kg/m2). High sensitivity CRP (hs-CRP) was classified according to AHA/CDC guidelines for CVD risk. Multinomial logistic regression was used to characterize the association of BMI change with categories of hs-CRP. Results: Table 1 shows BMI change and its associations with categories of hs-CRP. Multinomial logistic regression demonstrated that individuals who had high CRP in midlife at visit 2 had increased odds of both subsequent BMI gain and loss both in the next 6 years (visit 2 to visit 4) and in the following 15 years (visit 4 to visit 5). Inflammation in late midlife (visit 4, median age: 62) was also predictive of subsequent BMI gain and loss (to visit 5, median age: 75). Similar associations were seen after further adjustment for diabetes, hypertension, physical activity and smoking (p&lt;0.05). Conclusion: Elevated CRP was associated with subsequent BMI gain, but was more strongly associated with subsequent BMI loss in both midlife and older age. These findings suggest that inflammation is a marker associated with weight change that may help distinguish between healthy and unhealthy weight loss in middle-aged and older adults.

Whole-blood fatty acids and inflammation in European children: the IDEFICS Study.

Fatty acids are hypothesized to influence cardiovascular disease risk because of their effect on inflammation. The aim of this study is to assess the relationship between whole-blood fatty acids (WBFAs) and high-sensitivity C-reactive protein (hs-CRP) in European children. A total of 1401 subjects (697 boys and 704 girls) aged between 2 and 9 years from the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects in Children and infantS) study were measured in this cross-sectional analysis. The sample was divided into three categories of hs-CRP. Associations between WBFA and hs-CRP were assessed by logistic regression models adjusting for body mass index (BMI), country, age, breastfeeding, mother's education and hours of physical activity. Linoleic acid (LA) (P=0.013, 95% confidence interval (CI): 0.822-0.977) and sum of n-6 WBFA (P=0.029, 95% CI: 0.866-0.992) concentrations were associated with lower concentrations of hs-CRP in boys. In girls, a high ratio of eicosapentaenoic acid (EPA)/arachidonic acid (AA) was associated (P=0.018, 95% CI: 0.892-0.989) with lower hs-CRP concentrations. In contrast, sum of blood n-6 highly unsaturated fatty acids (P=0.012, 95% CI: 1.031-1.284), AA (P=0.007, 95% CI: 1.053-1.395) and AA/LA ratio (P=0.005, 95% CI: 1.102-1.703) were associated (P<0.05) with higher concentrations of hs-CRP in girls. The n-6 WBFAs (sum of n-6 FA and LA) were associated with lower hs-CRP in boys and with higher hs-CRP in girls (AA, sum of n-6 highly unsaturated and AA/LA ratio). More studies are needed to identify the optimal levels of WBFAs to avoid low-grade inflammation in children considering the differences by sex and BMI.

Abstract 17: The Association Between Erythrocyte n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) Content and Inflammation in Male Patients With Peripheral Artery Disease (PAD)

Objectives Dietary intake of n-3 PUFAs has been associated with cardiovascular disease, though the relationship to PAD is unclear. PAD patients have an increased burden of systemic inflammation. In a cross-sectional PAD cohort study, we evaluated the relationship between n-3 PUFAs content of red blood cells (omega-3 index) and biomarkers of systemic inflammation. Methods This was a prospective cohort study of patients (n=83) presenting to vascular surgery clinic for evaluation of PAD. The omega-3 index was measured using gas chromatography and inflammatory markers (hsCRP, IL-6, TNF-α and ICAM-1) via ELISA kits. We used linear regression to evaluate the independent association between the omega-3 index and inflammation. Results 70 patients had PAD while 13 were found to have a normal ankle-brachial index (ABI). Mean (±SD) age was 67 ± 7 years. Mean ABI was 0.85 ± 0.23. The omega-3 index decreased across defined AHA hsCRP categories (Figure 1, p=0.04). One percentage point decrease in the omega-3 index was associated with increases in CRP (14%, 95% CI 0, 25, p=0.04), IL6 (8%, 95% CI 1, 15, p=0.02) and possibly ICAM-1 (4%, 95% CI -1, 12, p=0.13), but not TNF-α. After adjusting for age, race, HDL, smoking status, ABI and the body-mass index, the omega-3 index remained significantly (negatively) associated with systemic inflammation as measured by hsCRP in a male population at risk or suffering from PAD (p=0.05). Conclusions In a contemporary cohort of patients with PAD, the omega-3 index was negatively associated with biomarkers of inflammation. Our findings suggest a rationale for future studies of dietary manipulation of omega-3 index to reduce inflammation in patients with PAD.

Abstract MP11: Elevated High Sensitivity C-Reactive Protein as a Risk Marker of the Attenuated Relationship Between Serum Cholesterol and Coronary Heart Disease at Older Age - Atherosclerosis Risk in Communities Study

Introduction: The relationship between serum cholesterol and coronary heart disease (CHD) risk is attenuated at older age, making it difficult to estimate risk in this age group. Hypothesis: We hypothesized that high sensitivity C-reactive protein (hs-CRP) would identify two subgroups of older individuals (≥65 years): one in whom cholesterol is less predictive of CHD and one in whom it is equally predictive compared to younger individuals. Methods: We calculated crude incident rates per 1,000 person-years and used adjusted Cox proportional hazards models to analyze cholesterol as a predictor of CHD in 8,947 participants with no known history of CHD who were stratified by age (53-64 or 65-75 years) and hs-CRP level (&lt;2 or ≥2 mg/L) at baseline. Results: Among younger participants, total serum cholesterol was significantly associated with an increased risk of CHD regardless of hs-CRP group HR 1.39 (95% CI 1.20-1.61) for hs-CRP &lt;2 mg/L and HR 1.37 (95% CI 1.22-1.53) for hs-CRP ≥2 mg/L. Among older participants with a low hs-CRP, total cholesterol had a similar association with CHD, HR 1.46 (95% CI 1.24-1.71), as in younger individuals. In contrast, among older individuals with higher hs-CRP, the association of CHD with total cholesterol was attenuated, HR 1.14 (95% CI 1.00-1.29), p-value for interaction = 0.02. Similar trends were observed between age groups and hs-CRP categories for LDL cholesterol. Conclusions: Among individuals aged 65-75 years, the association of cholesterol with CHD was strong in those with a low hs-CRP and weak in those with an elevated hs-CRP. Thus, in addition to its use as a risk factor, an elevated hs-CRP could be useful for stratifying the elderly population to aid in the interpretation of serum cholesterol in the prediction of subsequent CHD risk.

Effects of combination therapy with rosuvastatin and fenofibric acid in patients with mixed dyslipidemia and high-sensitivity C-reactive protein (≥2 mg/L)

Elevated levels of high-sensitivity C-reactive protein (hsCRP) correlate with an increased risk for cardiovascular events. Combination therapy with a statin and a fibrate may be more effective than statin monotherapy for reducing hsCRP, especially in patients with mixed dyslipidemia. To characterize the treatment effects of rosuvastatin and fenofibric acid combination therapy compared with individual monotherapies in mixed dyslipidemic patients with baseline hsCRP ≥2 mg/L versus <2 mg/L and to determine the effects of long-term treatment with rosuvastatin and fenofibric acid combination therapy on hsCRP and other lipids for patients with hsCRP ≥2 mg/L after treatment with rosuvastatin monotherapy. Data for the post hoc analysis were derived from two 12-week controlled studies and a 52-week extension study. Patients were treated with fenofibric acid 135 mg; rosuvastatin 5, 10, 20, or 40 mg; or rosuvastatin 5, 10, or 20 mg and fenofibric acid 135 mg in the controlled studies; and with rosuvastatin 20 mg and fenofibric acid 135 mg in the extension study. In this analysis, 65% (1416/2182) of patients had pretreatment baseline hsCRP ≥2 mg/L. Among all treatment groups, larger decreases in hsCRP were observed in patients with greater baseline hsCRP; however, improvements in other lipids/apolipoprotein were comparable between the baseline hsCRP categories. Among patients with high hsCRP (≥2 mg/L) remaining after 12 weeks of rosuvastatin 10, 20, or 40 mg monotherapy, hsCRP was reduced by ∼36% after switching to rosuvastatin 20mg and fenofibric acid 135 mg for up to 52 weeks, and ∼36% of patients shifted from hsCRP ≥2 mg/L to <2 mg/L. Combination therapy with rosuvastatin and fenofibric acid may be effective for improving the inflammatory biomarker, hsCRP as well as other lipid abnormalities in patients with mixed dyslipidemia and high hsCRP.

Sex related cardiovascular risk stratification based on quantification of atherosclerosis and inflammation

ObjectivesAn ongoing population-based cohort study was used to assess the prevalence of risk factors, signs of inflammation based on the degree of high sensitive C-reactive protein (hs-CRP) and subclinical atherosclerosis using electron beam computed tomography for detection of coronary artery calcification (CAC). We evaluated the sex related cardiovascular risk stratification based on quantification of subclinical atherosclerosis and inflammation. BackgroundThe National Cholesterol Education Program in Adult Treatment Panel III (NCEP ATP III) suggests using CAC and hs-CRP in individuals at intermediate risk. The effect on risk stratification was not yet tested in the general population. MethodsIn the Heinz Nixdorf Recall study 4066 (93.2%) subjects without and 280 (6.8%) of 4345 subjects with coronary artery disease (CAD) (age 45–75years) were screened in whom data for CAC, hs-CRP, and all risk factors for calculating the Framingham risk score (FRS) were available. This subset of participants was representative of the overall population. Age-adjusted prevalence rate ratios (RR) for prevalence of CAD in relation to risk factors were determined. Framingham risk score groups and NCEP ATP III-based risk categories were calculated. Alterations in risk classification were analyzed using three CAC and hs-CRP categories each: (1) CAC<100, 100–399 and ≥400 or >75th percentile, respectively, (2) hs-CRP≤1, 1–3, >3mg/L, and (3) a combined CAC and hs-CRP score. ResultsHighest RRs of CAD were found for high CAC versus low CAC in men (RR=18.2, 95% CI=10.6–31.3) and for the combined CAC+hs-CRP index in women (RR=11.0, 95% CI=5.1–23.6, both p<0.0001). For high versus low hs-CRP-values a significant RR was found for women only (RR=2.5, 95% CI=1.3–4.6, p<0.01). RRs for other risk factors like hyperlipidemia, HDL, smoking, BMI>30kg/m2 were much smaller showing sex differences as well. Thirty percent males and 71% females were classified as low NCEP ATP III risk, 38% and 20% as intermediate and 31% and 9% as high risk. Adding CAC and hs-CRP to NCEP ATP risk categories changed distribution of risk categories considerably with strong differences between sexes. This sex dependence in the magnitude of change in risk categories nearly vanished, when the combined index of CAC and hs-CRP was used. ConclusionsNCEP ATP III risk categories are significantly and sex-dependently altered using CAC and hs-CRP. CAC is suggested to be of highest value in men; hs-CRP seems to be of complementary value only in women. Measuring atherosclerotic inflammation may improve sex-related risk prediction in a general population.