Abstract 25: Six-year Change in C-reactive Protein Levels and Risk of Incident Diabetes, Cardiovascular Events and Mortality

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Christina M Parrinello ◽  
Pamela L Lutsey ◽  
Christie M Ballantyne ◽  
Aaron R Folsom ◽  
James S Pankow ◽  
...  

Background: High levels of C-reactive protein (CRP) are associated with cardiovascular disease, diabetes and mortality. It is unclear whether changes in CRP or persistently high CRP are associated with these outcomes beyond the baseline measure. Methods: We conducted a prospective cohort analysis of 10,229 participants from the ARIC Study with two measurements of CRP six years apart (at visits 2 and 4, 1990-92 and 1996-98, respectively). CRP was categorized into two groups using a standard cut-point for defining high levels (≥3 vs. <3 mg/L). Six-year change in CRP was categorized as: persistently not high (<3 mg/L), decreasing (≥3 to <3 mg/L), increasing (<3 to ≥3 mg/L), and persistently high (≥3 mg/L). Cox proportional hazards models were used to assess the association between visit 2 CRP, visit 4 CRP and six-year change in CRP and each of the following outcomes from visit 4 through 2010: diabetes, coronary heart disease, ischemic stroke, heart failure and all-cause mortality. Models were adjusted for traditional risk factors at visit 2. Sensitivity analyses additionally adjusted for visit 4 covariates. Results: Persons with CRP ≥3 mg/L at visit 2 or 4 had higher risk of each outcome compared to those with CRP <3 mg/L ( Table ). We observed higher risk of all outcomes in persons with persistently high CRP, and of all outcomes except stroke in persons with increasing CRP, compared to those with CRP <3 mg/L at both visits ( Table ). Persons whose CRP decreased from high to <3 mg/L did not have significantly increased risk of cardiovascular outcomes or diabetes compared to those with CRP persistently <3 mg/L. Results were similar after adjusting for visit 4 covariates. Conclusions: Persons with sustained high levels of CRP or whose CRP increased to high levels had higher risk of diabetes, cardiovascular disease, and death, while those whose levels decreased from high to moderate or low were at lower risk. Multiple measures of CRP may better characterize inflammatory status and provide more comprehensive information regarding long-term risk.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1508-1508
Author(s):  
Mengjie Yuan ◽  
R Taylor Pickering ◽  
Martha Singer ◽  
Lynn l Moore

Abstract Objectives Few studies have estimated the independent effects of butter and margarine on risk of cardiovascular disease (CVD). Our goal was to examine these effects as well as that of other fats and oils on risk of CVD and markers of cardiometabolic risk in subjects in the prospective Framingham Offspring Study. Methods Data from 2038 adults, who were free of CVD and diabetes through exam 5 were included. Intakes of butter, margarine, mayonnaise, oils, and shortening were assessed using 3-day diet records at exams 3 and 5. Concentrations of low-density lipoproteins (LDL), high-density lipoproteins (HDL), and their particle sizes were analyzed cross-sectionally at exam 5. Subjects were followed from exam 5 to 9 for incident CVD and type 2 diabetes (T2DM) (median follow-up, 16.9 years). Cox proportional hazards models were used to estimate risk of CVD and T2DM and generalized linear models were used to evaluate effects on other cardiometabolic outcomes, while adjusting for age, sex, pack-years of smoking, BMI, physical activity, intakes of other fats, hypertension and use of lipid-lowering medication. Intake of each type of dietary fat was categorized as low, moderate, or high using sensitivity analyses. Results Intake of &gt;5 g/day of butter (vs. non-consumers) had no effect on CVD risk but was associated with a non-statistically significant 24% lower risk of T2DM. In men, higher butter intake was linked with larger LDL and HDL particles sizes (P &lt; 0.01 for both) and a lower LDL: HDL ratio (P &lt; 0.01). Consuming &gt;7 g/day (vs. ≤2) of margarine was associated with a 48% (95% CI: 1.03–2.13) increased risk of CVD and a 68% (95% CI: 1.00–2.82) higher risk of T2DM in women. In men, higher margarine intake was associated with much weaker, non-statistically significant increased risks of CVD and T2DM. Finally, total intake of oils (&gt;7 vs. ≤2 g/day) was associated with a strong reduced risk of T2DM (HR: 0.55; 95% CI: 0.36–0.85) in men but not women. There was no effect of margarine or oils on lipid particle sizes in either men or women. Conclusions While butter intake had no adverse effect on risk of CVD in either men or women, it was beneficially associated with lipid profiles in men. In women, higher intakes of margarine but not butter were associated with increased risks of both CVD and T2DM. Finally greater oil consumption led to lower risks of T2DM in men. Funding Sources NHLBI National Dairy Council.


2018 ◽  
Vol 3 (1) ◽  
pp. 46 ◽  
Author(s):  
Fred Richard Sattler ◽  
Daniel Chelliah ◽  
Xingye Wu ◽  
Alejandro Sanchez ◽  
Michelle A. Kendall ◽  
...  

Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death.Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3. The case-cohort sample consisted of 51 randomly selected participants, whose stored plasma was tested for C-reactive protein, cytokines, chemokines, and nutritional markers. Cox proportional hazards models were used to assess the association of nutritional, inflammatory, and immunomodulatory markers for survival.Results: The case-cohort sample was similar to the 282 participants within the parent cohort with CD4 < 50 cells/mm3. In the case cohort, 7 (14%) had BMI < 16.5 (kg/m2) and 17 (33%) had BMI 16.5-18.5(kg/m2). Risk of death was increased per 1 IQR width higher of log10 transformed level of C-reactive protein (adjusted hazard ratio (aHR) = 3.42 [95% CI = 1.33-8.80],P = 0.011), interferon gamma (aHR = 2.46 [CI = 1.02-5.90], P = 0.044), MCP-3 (3.67 [CI = 1.08-12.42], P = 0.037), and with IL-15 (aHR = 2.75 [CI = 1.08-6.98], P = 0.033) and IL-17 (aHR = 3.99 [CI = -1.06-15.07], P = 0.041). BMI, albumin, hemoglobin, and leptin levels were not associated with risk of death.Conclusions: Unlike patients only infected with M. tuberculosis for whom malnutrition and low BMI increase the risk of death, this relationship was not evident in our dually infected patients. Risk of death was associated with significant increases in markers of global inflammation along with soluble biomarkers of innate and adaptive immunity.


2020 ◽  
Vol 9 (11) ◽  
pp. 3616
Author(s):  
Carolina Gracia-Iguacel ◽  
Emilio González-Parra ◽  
Ignacio Mahillo ◽  
Alberto Ortiz

Background: In hemodialysis patients, extracellular water (ECW) overload predicts all-cause and cardiovascular mortality. The primary aim of the present study was to analyze changes in post-dialysis (i.e., following removal of excess ECW) ECW, intracellular water (ICW), and the overhydration (OH) parameter over time. Additionally, the association of these parameters with mortality was explored. Patients and methods: Prospective study of prevalent hemodialysis patients (n = 124) followed for a median of 20 (interquartile range (IQR) 8–31) months. In three visits, inflammation (C-reactive protein) and post-dialysis fluid status (bioimpedance, BIS) were assessed. Results: During follow-up, the overhydration (OH) parameter increased (−0.696 ± 1.6 vs. 0.268 ± 1.7 L; p = 0.007) at the expense of a decrease in intracellular water (ICW) (19.90 ± 4.5 vs. 18.72 ± 4.1 24 L; p = 0.006) with a non-significant numerical increase in ECW/ICW ratio (0.795 ± 0.129 vs. 0.850 ± 0.143; p = 0.055). Baseline ICW positively correlated with muscle mass and energy intake and negatively with C-reactive protein and it was lower in those who died than in survivors (15.09 ± 2.36 vs. 18.87 ± 4.52 L; p = 0.004). In Kaplan–Meier analysis, patients with low baseline ICW (≤17 L) and high ECW/ICW ratio (≥0.84) were at an increased risk of death. Baseline ICW was also associated with the risk of death in adjusted Cox proportional hazards models (HR 0.62 (0.40–0.98) p = 0.04). Conclusions: In hemodialysis patients, the post-dialysis OH parameter increased over time while ICW decreased, without changes in ECW. Low baseline post-dialysis ICW correlated with muscle wasting and inflammation and was an independent risk factor for mortality.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wei Zhang ◽  
Jaime L Speiser ◽  
Miguel Cainzos Achirica ◽  
Khurram Nasir ◽  
Michael Tsai ◽  
...  

Introduction: Lipoprotein (a) (Lp(a)) and inflammation, as represented by elevated high-sensitivity C-reactive protein (hsCRP) concentration, are both considered as risk-enhancers in the 2018 AHA/ACC Cholesterol guidelines. However, little is known as to whether the association of Lp(a) with atherosclerotic cardiovascular disease (ASCVD) risk is modified by inflammation. Objective: We assessed whether hsCRP modifies the association of Lp(a) with ASCVD risk. Methods: MESA participants with baseline hsCRP and Lp(a) levels were included. Incident ASCVD events were ascertained from baseline through 2017. Time to incident ASCVD was analyzed using Kaplan Meir curves. Cox proportional hazards models were used to assess the association between Lp(a), hsCRP, and time to ASCVD events adjusting for covariates. Results: The study included 4,654 participants with mean age of 62 and 52.5% females (1,702 Caucasians, 557 Chinese Americans, 1,336 African Americans and 1,059 Hispanics). With a mean 13.6-year follow-up, 676 ASCVD events occurred among 4,609 participants (Figure 1). In participants with hsCRP <2mg/L, the association of Lp(a) (per 1 Log unit increase) and risk for ASCVD as represented by hazard ratio (HR) and 95%CI was 1.01 (0.79, 1.28). In subjects with hsCRP ≥2mg/L, the risk increased to 1.26 (1.01, 1.58). When compared to the reference group with Lp(a) <50mg/dL and hsCRP <2mg/L, the risk for ASCVD in participants with Lp(a) ≥50mg/dL and hsCRP <2mg/L was 1.13 (0.85, 1.50) and in those with Lp(a) <50mg/dL and hsCRP ≥2mg/L was 1.09 (0.92, 1.31). The risk increased significantly to 1.62 (1.26, 2.07) in participants with Lp(a) ≥50mg/dL and hsCRP ≥2mg/L. Conclusions: Lp(a)-related ASCVD risk is modified by hsCRP levels. The findings of this analysis suggest that Lp(a) may serve as a risk enhancing factor in individuals with hsCRP level ≥2mg/L. Future studies are needed to determine whether Lp(a) is associated with risk of ASCVD in the absence of subclinical inflammation.


2019 ◽  
Vol 149 (8) ◽  
pp. 1451-1459 ◽  
Author(s):  
Emiko Okada ◽  
Toru Shirakawa ◽  
Nitin Shivappa ◽  
Kenji Wakai ◽  
Koji Suzuki ◽  
...  

ABSTRACT Background The Dietary Inflammatory Index (DII) is a comprehensive, literature-derived index for assessing the effect of dietary constituents on inflammatory biomarkers. Several studies have shown an association between DII score and mortality, but there are limited prospective studies in Asian populations. Objectives The aim of this study was to investigate the association between DII score and risk of all-cause, total cardiovascular disease (CVD), stroke, coronary heart disease (CHD), total cancer, digestive cancer, and noncancer/non-CVD mortality in the Japanese population. Methods A total of 58,782 Japanese participants aged 40–79 y who were enrolled in the Japan Collaborative Cohort Study during 1988–1990 were included in the analysis. DII scores were calculated based on a food-frequency questionnaire. HRs and 95% CIs for mortality according to DII quintiles were estimated using Cox proportional hazards models. Results During the median follow-up period of 19.3 y, a total of 11,693 participants died. The multivariable HR for all-cause mortality for the highest compared with the lowest DII quintiles was 1.13 (95% CI: 1.05, 1.21). For CVD mortality, the highest multivariable HRs were 1.30 (95% CI: 1.13, 1.49), 1.29 (95% CI: 1.05, 1.59), and 1.30 (95% CI: 0.96, 1.76) for total CVD, stroke, and CHD, respectively. No significant associations were observed between DII and risk of total cancer, digestive cancer, and noncancer/non-CVD mortality. Conclusion Our findings suggest that a higher DII was associated with an increased risk of all-cause and CVD mortality among Japanese adults.


Author(s):  
Hao-Ming Li ◽  
Shi-Zuo Liu ◽  
Ying-Kai Huang ◽  
Yuan-Chih Su ◽  
Chia-Hung Kao

Appendicitis is a common surgical condition for children. However, environmental effects, such as piped water supply, on pediatric appendicitis risk remain unclear. This longitudinal, nationwide, cohort study aimed to compare the risk of appendicitis among children with different levels of piped water supply. Using data from Taiwan Water Resource Agency and National Health Insurance Research Database, we identified 119,128 children born in 1996–2010 from areas of the lowest piped water supply (prevalence 51.21% to 63.06%) as the study cohort; additional 119,128 children of the same period in areas of the highest piped water supply (prevalence 98.97% to 99.63%) were selected as the controls. Both cohorts were propensity-score matched by baseline variables. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of appendicitis in the study cohort compared to the controls by Cox proportional hazards regression. The study cohort had a raised overall incidence rates of appendicitis compared to the control cohort (12.8 vs. 8.7 per 10,000 person-years). After covariate adjustment, the risk of appendicitis was significantly increased in the study cohort (adjusted HR = 1.46, 95% CI: 1.35, 1.58, p < 0.001). Subgroup and sensitivity analyses showed consistent results that children with low piped water supply had a higher risk of appendicitis than those with high piped water supply. This study demonstrated that children with low piped water supply were at an increased risk of appendicitis. Enhancement of piped water availability in areas lacking adequate, secure, and sanitized water supply may protect children against appendicitis.


2019 ◽  
Vol 45 (1) ◽  
pp. 84-94
Author(s):  
Jingli Gao ◽  
Aitian Wang ◽  
Xiaolan Li ◽  
Junjuan Li ◽  
Hualing Zhao ◽  
...  

Background and Objectives: This study was to characterize the association of cumulative exposure to increased high-sensitivity C-reactive protein (hs-CRP) with chronic kidney diseases (CKD). Methods: We included 35,194 participants with hs-CRP measured at three examinations in 2006, 2008, 2010. Participants were classified into nonexposed group (hs-CRP <3.0 mg/L in all 3 examinations), 1-exposed group (hs-CRP ≥3.0 mg/L in 1 of the 3 examinations), 2-exposed group (hs-CRP ≥3.0 mg/L in 2 of the 3 examinations), and 3-exposed group (hs-CRP ≥3.0 mg/L in 3 examinations). Cox proportional hazards models were used to assess the association of cumulative hs-CRP with incident CKD. CKD includes an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or urinary protein positive. Results: The study showed the risk of CKD as the number of years of exposure to hs-CRP increases. Participants in 3-exposed group had significantly increased CKD risk with hazard ratio (HR) (95% confidence interval, CI) of 1.70 (1.49–1.93), in comparison with 1.47 (1.34–1.62) for participants in the 2-exposed group, and 1.08 (1.00–1.16) for those in the 1-exposed group (p < 0.01); meanwhile, the similar and significant associations were also observed for eGFR <60 mL/min/1.73 m2, proteinuria positive, in participants of the 3-exposed group in comparison with the nonexposed group, with respective HRs (95% CI) of 1.27 (1.01–1.58) and 2.27 (1.87–2.76). Conclusions: Cumulative exposure to hs-CRP was associated with a subsequent increased risk of CKD and was of great value to risk prediction.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7147
Author(s):  
Mirjam Bachler ◽  
Tobias Hell ◽  
Lukas Schausberger ◽  
Christine Schlömmer ◽  
Volker Schäfer ◽  
...  

BackgroundSepsis is characterized by a pro-inflammatory and pro-coagulatory shift which can induce life-threatening complications. Close monitoring and risk stratification of sepsis patients is crucial for proper treatment and consequently patient outcome. Therefore, this study focuses on the response patterns of inflammatory and coagulatory parameters used in clinical routines to estimate the course of sepsis.MethodsA total of 1,110 patients diagnosed with sepsis were retrospectively analyzed to identify response patterns for risk stratification of routine parameters measured at the peak level of C-reactive protein. Cluster analysis was used and the differences in the patient characteristics and 28-day survival were assessed. Cox proportional hazards regression model for survival stratified by the clusters was performed.ResultsThe analyses revealed the parameters to have five distinct response patterns. These clusters reflect the etiology as well as the course of sepsis associated with different mortalities. Here, impairment of the liver plays a crucial role in the ability to appropriately respond to sepsis. Of the routinely measured parameters, C-reactive protein and antithrombin seem to be unspecific for stratification of septic patients. Adjusted for the individual clusters, survival was associated with an increase in fibrinogen (p = 0.0042), platelets (p = 0.0003) and PT (p = 0.001) as well as a decrease in leukocytes (p = 0.034).ConclusionsThis study reveals that patients have distinct response patterns of inflammatory and coagulatory parameters depending on disease etiology. These patterns are associated with different mortalities although the patients have similar levels of C-reactive protein. Independently of the type of response, good coagulatory capacity seems to be crucial for patient survival.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Dongshan Zhu ◽  
Hsin-Fang Chung ◽  
Annette Dobson ◽  
Nirmala Pandeya ◽  
Gita Mishra

Introduction: Evidence from clinical trials and observational studies on the relationship between menopausal hormone therapy (MHT) and cardiovascular disease (CVD) risk has been discordant. Hypothesis: We hypothesized that the association between MHT and risk of CVD might be affected by both age at menopause and age when initiated MHT. Methods: We harmonised and pooled individual-level data from 15 studies across five countries/regions (Australia, Scandinavia, USA, Japan, and UK). Postmenopausal women who had reported their MHT status (user or non-user) and CVD status (occurred or not, including coronary heart disease (CHD) and stroke) were included. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the association between MHT use and incident CVD. We stratified the analyses by age when initiated MHT and age at natural menopause to examine the interaction between MHT, age initiated MHT, and age at menopause on incident CVD. Results: Overall, 190 625 postmenopausal women were included. We identified 10 601 incident CVD events, including 7615 CHD and 3543 strokes. Around 39% (74 585) women were MHT users. Compared to non-users of MHT, women who were MHT users had 10% higher risk of incident CVD (HR 1.10, 95% CI 1.06-1.14), with HR (95% CI) of (1.15, 1.10-1.20) for CHD and (1.02, 0.96-1.09) for stroke. After stratifying by age at natural menopause, women who experienced menopause after age 45 years and took MHT had around 15% higher risk of CHD, while the significant association with incident stroke was only observed in women who had menopause after 55 years (1.16, 1.01-1.33). After a further stratification by age initiated MHT, we found the significant associations between MHT users and incident CVD were only observed in women who experienced menopause after age 45 years and took MHT at age 60 years or old (Table 1). Conclusions: Postmenopausal women who experienced natural menopause after age 45 years and took MHT after age 60 years had increased risk of incident CVD.


2015 ◽  
Vol 95 (12) ◽  
pp. 1660-1667 ◽  
Author(s):  
A. Williams Andrews ◽  
Dongmei Li ◽  
Janet K. Freburger

Background Little is known about the use of rehabilitation in the acute care setting and its impact on hospital readmissions. Objective The objective of this study was to examine the association between the intensity of rehabilitation services received during the acute care stay for stroke and the risk of 30-day and 90-day hospital readmission. Design A retrospective cohort analysis of all acute care hospitals in Arkansas and Florida was conducted. Methods Patients (N=64,065) who were admitted for an incident stroke in 2009 or 2010 were included. Rehabilitation intensity was categorized as none, low, medium-low, medium-high, or high based on the sum and distribution of physical therapy, occupational therapy, and speech therapy charges within each hospital. Cox proportional hazards regression was used to estimate hazard ratios, controlling for demographic characteristics, illness severity, comorbidities, hospital variables, and state. Results Relative to participants who received the lowest intensity therapy, those who received higher-intensity therapy had a decreased risk of 30-day readmission. The risk was lowest for the highest-intensity group (hazard ratio=0.86; 95% confidence interval=0.79, 0.93). Individuals who received no therapy were at an increased risk of hospital readmission relative to those who received low-intensity therapy (hazard ratio=1.30; 95% confidence interval=1.22, 1.40). The findings were similar, but with smaller effects, for 90-day readmission. Furthermore, patients who received higher-intensity therapy had more comorbidities and greater illness severity relative to those who received lower-intensity therapy. Limitations The results of the study are limited in scope and generalizability. Also, the study may not have adequately accounted for all potentially important covariates. Conclusions Receipt of and intensity of rehabilitation therapy in the acute care of stroke is associated with a decreased risk of hospital readmission.


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