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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.

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.

SUBMITTER: Kim JY

PROVIDER: S-EPMC8475026 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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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 Jae Young JY Park Jung Tak JT Kim Hyung Woo HW Chang Tae-Ik TI Kang Ea Wha EW Ahn Curie C Oh Kook-Hwan KH Lee Joongyub J Chung Wookyung W Kim Yong-Soo YS Kim Soo Wan SW Yoo Tae-Hyun TH Kang Shin-Wook SW Han Seung Hyeok SH

Journal of the American Heart Association 20210807 16

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 hi ...[more]

PMID: 34369187

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Project description:Background Conventional "low-density lipoprotein cholesterol (LDL-C)" assays measure cholesterol content in both low-density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of "LDL-C" and corrected LDL-C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline-recommended LDL-C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from "LDL-C" to obtain corrected LDL-C values (LDL-Ccorr30). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual-patient-data meta-analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow-up). When comparing top versus bottom quartiles, the multivariable-adjusted hazard ratio for cardiovascular disease was significant for "LDL-C" (1.17; 95% CI, 1.05-1.31; P=0.005) but not for LDL-Ccorr30 (1.07; 95% CI, 0.93-1.22; P=0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline-recommended LDL-C categories when using LDL-Ccorr30 was assessed. In "LDL-C" categories of 70 to <100, 100 to <130, 130 to <190, and ≥190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL-C categories when LDL-Ccorr30 was used: 30.2% (30.0%-30.4%), 35.1% (34.9%-35.4%), 32.9% (32.6%-33.1%), and 41.1% (40.0%-42.2%), respectively. Conclusions "LDL-C" was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL-C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.

Project description:BackgroundThe ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is a novel marker related to atherosclerosis, but its role in diabetic kidney disease (DKD) remains unclear. This study investigated the relationship between NHHR and DKD risk in patients with type 2 diabetes mellitus (T2DM) and evaluated its potential as a marker for early DKD screening.MethodsData from adults with T2DM participating in the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2018 were analyzed. Demographic information, laboratory tests, and other relevant information were collected. To evaluate the correlation between NHHR levels and DKD risk, weighted multivariable logistic regression and weighted restricted cubic spline (RCS) analyses were employed. Furthermore, threshold effect analysis was employed to further explore the relationship at different NHHR levels, and subgroup analyses validated the results.ResultsThe study enrolled a total of 3,243 participants, comprising 1,258 individuals with DKD (38.79%) and 1,985 individuals without DKD (61.21%). The multivariable logistic regression analysis showed that T2DM patients with higher NHHR levels exhibited a 45% reduction in the risk of developing DKD in comparison to those with lower NHHR levels (Q2 vs. Q1: OR 0.55, 95% CI 0.40-0.76). The weighted RCS analysis revealed a nonlinear correlation between NHHR and the risk of DKD in patients with T2DM (P for nonlinear = 0.003), with the RCS plot exhibiting an L-shaped association. A negative association was observed between NHHR levels and the risk of DKD when NHHR was ≤2.82 (OR 0.63, 95% CI 0.49-0.83). A statistically significant correlation between NHHR and DKD risk was not observed when NHHR was >2.82. The subgroup analyses indicated that age may have an interaction effect on this association at higher NHHR levels (p for interaction<0.05).ConclusionOur findings revealed a non-linear relationship between the NHHR levels and the risk of DKD in adult T2DM patients in the United States. Managing the NHHR levels in the right range in T2DM patients can help reduce the risk of DKD. This suggests that NHHR may be a valuable and easily measurable biomarker for identifying those at risk for DKD, thereby promoting early intervention and improved disease management.

Dataset Information

Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.

Publications

Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.

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