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Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.
Kim, JY, Park, JT, Kim, HW, Chang, TI, Kang, EW, Ahn, C, Oh, KH, Lee, J, Chung, W, Kim, YS, et al
Journal of the American Heart Association. 2021;(16):e021731
Abstract
Background The function of high-density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high-density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high-density lipoprotein cholesterol (HDL-C) level. Presence of inflammation was defined by hs-CRP (high-sensitivity C-reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person-years of follow-up, overall incidence of the primary outcome was 15.8 per 1000 person-years. In multivariable Cox analysis after adjusting for confounders, HDL-C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL-C for risk of extended major adverse cardiovascular events (P=0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL-C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. Conclusions The association between HDL-C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.
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High-Sensitivity C-Reactive Protein Discordance With Atherogenic Lipid Measures and Incidence of Atherosclerotic Cardiovascular Disease in Primary Prevention: The ARIC Study.
Quispe, R, Michos, ED, Martin, SS, Puri, R, Toth, PP, Al Suwaidi, J, Banach, M, Virani, SS, Blumenthal, RS, Jones, SR, et al
Journal of the American Heart Association. 2020;(3):e013600
Abstract
Background Inflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high-sensitivity C-reactive protein) is prognostic across various levels of atherogenic lipid measures such as low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high-density lipoprotein cholesterol in primary prevention is unknown. Methods and Results We studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996-1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low-density lipoprotein cholesterol + non-high-density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high-density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow-up of 18.4 (12.8-19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09-1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18-1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (≥7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use. Conclusions Our findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.
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Prospective association of physical activity and inflammatory biomarkers in older adults from the PREDIMED-Plus study with overweight or obesity and metabolic syndrome.
Fuentes, GC, Castañer, O, Warnberg, J, Subirana, I, Buil-Cosiales, P, Salas-Salvadó, J, Corella, D, Serra-Majem, L, Romaguera, D, Estruch, R, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(10):3092-3098
Abstract
BACKGROUND There is limited prospective evidence on the association between physical activity (PA) and inflammation in older adults. Our aim was to assess the associations between changes in PA and changes in the inflammatory profile in older individuals who are overweight or obese. METHODS This prospective study included 489 men and women, aged 55-75 years, from the PREDIMED-Plus trial. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), monocyte chemo-attractant protein-1 (MCP-1), C-peptide, high-sensitivity C-reactive protein (hs-CRP), leptin, and regulated on activation, normal T-cell expressed and secreted chemokine (RANTES) were obtained from fasting blood samples and a composite inflammatory score based on these biomarkers was calculated. Physical activity was measured by a validated questionnaire. All measures were taken at baseline and one-year follow-up. RESULTS Multiple linear regression models showed an association between an increase in total PA and a decrease in the inflammatory score (p = 0.012), which was particularly driven by a decrease in C-peptide (p = 0.037). Similarly, the inflammatory score decreased with increasing moderate PA (p = 0.001), and moderate-to-vigorous PA (p = 0.006). CONCLUSIONS Increases in total PA, moderate and moderate-to-vigorous PA were associated with a decrease in the inflammatory profile of obese or overweight older individuals. This finding is relevant for PA recommendations and public health strategies. CLINICAL TRIAL REGISTRY Clinical trial identifier: International Standard Randomized Controlled Trial 89898870.
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Inflammatory responses relate to distinct bronchoalveolar lavage lipidome in community-acquired pneumonia patients: a pilot study.
Zheng, Y, Ning, P, Luo, Q, He, Y, Yu, X, Liu, X, Chen, Y, Wang, X, Kang, Y, Gao, Z
Respiratory research. 2019;(1):82
Abstract
BACKGROUND Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Antibiotics are losing their effectiveness due to the emerging infectious diseases, the scarcity of novel antibiotics, and the contributions of antibiotic misuse and overuse to resistance. Characterization of the lipidomic response to pneumonia and exploring the "lipidomic phenotype" can provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments. METHODS Lipid profiles of bronchoalveolar lavage fluid (BALF) samples were generated through untargeted lipidomic profiling analysis using high-performance liquid chromatography with mass spectrometry (HPLC-MS). Principal component analysis (PCA) was applied to identify possible sources of variations among samples. Partitioning clustering analysis (k-means) was employed to evaluate the existence of distinct lipidomic clusters. RESULTS PCA showed that BALF lipidomes differed significantly between CAP (n = 52) and controls (n = 68, including 35 healthy volunteers and 33 patients with non-infectious lung diseases); while no clear separation was found between severe CAP and non-severe CAP cases. Lactosylceramides were the most prominently elevated lipid constituent in CAP. Clustering analysis revealed three separate lipid profiles; subjects in each cluster exhibited significant differences in disease severity, incidence of hypoxemia, percentages of phagocytes in BALF, and serum concentrations of albumin and total cholesterol (all p < 0.05). In addition, SM (d34:1) was negatively related to macrophage (adjusted r = - 0.462, p < 0.0001) and PE (18:1p/20:4) was positively correlated with polymorphonuclear neutrophil (PMN) percentages of BALF (adjusted r = 0.541, p < 0.0001). The 30-day mortality did not differ amongst three clusters (p < 0.05). CONCLUSIONS Our data suggest that specific lower airway lipid composition is related to different intensities of host inflammatory responses, and may contribute to functionally relevant shifts in disease pathogenesis in CAP individuals. These findings argue for the need to tailor therapy based on specific lipid profiles and related inflammatory status. TRIAL REGISTRATION ClinicalTrials.gov (NCT03093220). Registered on 28 March 2017 (retrospectively registered).
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Mid-arm circumference, body fat, nutritional and inflammatory biomarkers, blood glucose, dialysis adequacy influence all-cause mortality in hemodialysis patients: A prospective cohort study.
Duong, TV, Wu, PY, Wong, TC, Chen, HH, Chen, TH, Hsu, YH, Peng, SJ, Kuo, KL, Liu, HC, Lin, ET, et al
Medicine. 2019;(12):e14930
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Abstract
Hemodialysis patients are at the high risk for morbidity and mortality. Evaluation and management of body composition and biochemical values are important to improve dialysis outcomes. We aimed to examine the effects of the mid-arm circumference, body fat, nutritional and inflammatory biomarkers, blood glucose, and dialysis adequacy on the mortality.A prospective cohort study was conducted on 375 patients from 7 hospital-based dialysis centers. At baseline between September 2013 and April 2017, we assessed patients' characteristics using chart review, body composition using the bioelectrical impedance analysis, and biochemical parameters using available laboratory tests. Patients were followed-up for all-cause mortality until April 2018. Kaplan-Meier Curves with Log-rank test, and Cox proportional hazards models were used to analyze the effects of assessed factors on the mortality.During the median of follow-up time of 1.4 (1.0-3.2) years, 47 (12.5%) patients died. In the multivariate analysis, mid-arm circumference (hazard ratio, HR, 0.90; 95% confidence interval, 95%CI, 0.82-0.99; P = .036), body fat mass (HR, 0.95; 95%CI, 0.91-1.00; P = .031), percent body fat (HR, 0.96; 95%CI, 0.92-0.99; P = .024), serum creatinine (HR, 0.81; 95%CI, 0.68-0.96; P = .015), and eKt/V (HR, 0.07; 95%CI, 0.01-0.33; P = .001) reduced the mortality risk. Inflammation (HR, 2.90; 95%CI, 1.59-5.27; P < .001), hyperglycemia (HR, 2.16; 95%CI, 1.06-4.40; P = .033), and low serum uric acid (HR, 2.22; 95%CI, 1.15-4.31; P = .018) increased the death risk.In hemodialysis patients, the higher values of the mid-arm circumference, body fat, serum creatinine, uric acid, and dialysis adequacy were associated with lower mortality, whereas, inflammation and hyperglycemia associated with higher mortality.