High-density Lipoprotein Cholesterol Variability Research Articles

Greater variability in HDL-C was associated with an increased risk of cognitive decline in the middle- and elderly Chinese: A cohort study

BackgroundPrevious studies into relationship between high-density lipoprotein cholesterol (HDL-C) and cognitive decline were constrained to a single measurement, leaving the association between HDL-C variability and risk of cognitive decline unclear. MethodsWe identified 5930 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were devoid for stroke, dementia, and memory-related diseases at baseline and underwent a minimum of 2 sequential health examinations during 2011-2015. Variability in HDL-C was defined as (1) variability independent of the mean (VIM), (2) average real variability (ARV), and (3) standard deviation (SD) of HDL-C change from baseline and follow-up visits. Cognitive function was evaluated in 2018 by Mini-mental state examination (MMSE) in the Chinese version. Logistic regression was employed to explore the association between HDL-C variability and cognitive decline. Odd ratios (OR) and 95 % confidence intervals (CI) were reported. ResultsThe study included participants from CHARLS, mean age of 57.84±8.44 years and 44 % male. After adjustment for covariates, the highest quartile of VIM was associated with an increased risk of cognitive decline [OR:1.049, 95 %CI: 1.014-1.086] compared to the lowest quartile. For each SD increment of VIM, the OR was 1.015 (95 %CI:1.003-1.027). Strong dose-response relationships were identified (P for trend: 0.005). Consistent results were obtained for other measures of HDL-C variability (ARV and SD). Similar patterns were identified in different dimensions of cognition. ConclusionsElevated HDL-C variability was associated with increased cognitive decline risk. Strategies to reducing HDL-C variability may lower the risks of cognitive decline among the general population.

Abstract P264: HDL-C Variability and Peripheral Artery Disease

Background: Growing evidence has recognized the clinical implications of lipid variability in relation to cardiovascular disease and adverse outcomes. However, data on the association between lipid variability and the risk of incident peripheral artery disease (PAD) remain scarce compared to other manifestations like coronary artery disease and stroke. Methods: We conducted a study using data from the Chang Gung Research Database in Taiwan. A total of 93,948 patients diagnosed with hyperlipidemia between 2007 and 2013 who had at least one lipid measurement annually for four consecutive years were included in this study. Lipid levels, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides, as well as their visit-to-visit variability (average real variability, ARV), were calculated over the four-year period. Patients were followed up until December 31, 2019, for the development of incident PAD. Results: During a mean follow-up of 5.9 years, 2,735 (2.5%) of the patients had incident PAD. The mean levels of the four lipids were all significantly associated with the development of incident PAD. However, only HDL-C ARV showed a significant association with an increased risk of incident PAD, independent of traditional risk factors for atherosclerosis and lipid-lowering therapy (adjusted hazard ratio: 1.13; 95% confidence interval: 1.004-1.27 for the comparison between patients in the highest and lowest quartile of HDL-C ARV; P for trend = 0.002). A sensitivity analysis using the variability independent of the mean as the HDL-C variability index confirmed this association. The study result was consistent across all subgroups analyzed. Conclusions: In this multi-institutional database analysis, visit-to-visit variability in HDL-C was significantly associated with the risk of incident PAD, independent of traditional risk factors for atherosclerosis, mean lipid levels, and the use of lipid-lowering therapy. Absolute levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were all significantly associated with the development of incident PAD. Visit-to-visit variability in HDL-C was significantly linked to the risk of incident PAD, irrespective of traditional atherosclerosis risk factors, mean lipid levels, and lipid-lowering therapy use.

Association between visit-to-visit lipid variability and risk of ischemic heart disease: a cohort study in China.

To explore the associations between visit-to-visit lipid variability and risk of ischemic heart disease (IHD) in a population-based cohort in China. We evaluated lipid variability in 30,217 individuals from the Yinzhou Health Information System who had ≥3 recorded lipid measurements during 2010-2014. We used various indicators including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV) to quantify the variability in triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, a total of 1305 participants with IHD were identified during the follow-up of 194,421 person-years. Subjects in Q4 had a 21% elevated risk of IHD (HR = 1.21, 95% CI: 1.03-1.41) for LDL-C variability (CV) compared with the reference (Q1). The HRs for Q4 vs Q1 were 1.21 (95% CI: 1.04-1.42) for HDL-C variability, and 1.28 (95% CI: 1.10-1.50) for TC variability. However, no association was observed between triglycerides variability and risk of IHD. Higher variability in LDL-C, HDL-C, and TC levels was associated with an elevated risk of IHD, suggesting that lipid variability could be considered as an independent risk factor of IHD.

Lipid Variability and Risk of Cardiovascular Diseases and All-Cause Mortality: A Systematic Review and Meta-Analysis of Cohort Studies.

No consensus has yet been reached on the associations of lipid variability (LV) with cardiovascular diseases (CVDs) and all-cause mortality. We aimed to quantify the associations of different types and metrics of LV with CVDs and all-cause mortality. PubMed, Medline, and Embase databases were searched for eligible cohort studies published until 14 December 2021. Lipids included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Metrics of variability included standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM). The primary outcomes were CVDs and all-cause mortality. Random-effects meta-analysis was used to generate a summary of the relative risks (SRRs). Sources of heterogeneity were explored by subgroup analysis and meta-regression. A total of 11 articles based on seven cohorts were included. Participants in the top quartile of TC variability had an increased risk of CVDs (vs. bottom quartile: TC-CV: SRR 1.29, 95% CI 1.15-1.45; TC-SD: 1.28, 1.15–1.43; TC-VIM: 1.26, 1.13–1.41, respectively) and all-cause mortality (vs. bottom quartile: TC-CV: 1.28, 1.15–1.42; TC-SD: 1.32, 1.22–1.44; TC-VIM: 1.32, 1.25–1.40, respectively). Participants in the top quartile of HDL-C variability had an increased risk of CVDs (vs. bottom quartile: HDL-C-CV: 1.11, 1.07–1.15; HDL-C-SD: 1.18, 1.02–1.38; HDL-C-VIM: 1.18, 1.09–1.27, respectively) and all-cause mortality (vs. bottom quartile: HDL-C-CV: 1.29, 1.27–1.31; HDL-C-SD: 1.24, 1.09–1.41; HDL-C-VIM: 1.25, 1.22–1.27, respectively). LDL-C variability was also associated with an increased risk of CVDs (for top vs. bottom quartile; LDL-C-SD: 1.09, 1.02–1.17; LDL-C-VIM: 1.16, 1.02–1.32, respectively) and all-cause mortality (for top vs. bottom quartile; LDL-C-CV: 1.19, 1.04–1.36; LDL-C-SD: 1.17, 1.09–1.26, respectively). The relationships of TG variability with the risk of CVDs and all-cause mortality were inconclusive across different metrics. The effects of SRR became stronger when analyses were restricted to studies that adjusted for lipid-lowering medication and unadjusted for mean lipid levels. These findings indicate that the measurement and surveillance of lipid variability might have important clinical implications for risk assessment of CVDs and all-cause mortality.

Genetic Determinants of Visit-to-Visit Lipid Variability: Genome-Wide Association Study in Statin-Naïve Korean Population.

Background and AimThere is a growing evidence that fluctuation in lipid profiles is important in cardiovascular outcomes. We aimed to identify single nucleotide polymorphism (SNP) variants associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) variability in statin-naïve Korean subjects and evaluate their associations with coronary atherosclerosis.MethodsIn statin-naïve subjects from Gene-Environment of Interaction and phenotype cohort, we performed genome-wide association studies of lipid variability; the discovery (first) and replication (second) sets included 4,287 and 1,086 subjects, respectively. Coronary artery calcium (CAC) score and degree of coronary artery stenosis were used as outcome measures. Cholesterol variability was determined by standard deviation and average successive variability, and significant coronary atherosclerosis was defined as CAC score ≥400 or coronary stenosis ≥70%.ResultsMean HDL-C and LDL-C level were 54 ± 12 and 123 ± 30 mg/dL in the first set and 53 ± 12 and 126 ± 29 mg/dL in the second set. APOA5 rs662799 and APOA5 rs2266788 were associated with LDL-C variability and PXDNL rs80056520, ALDH2 rs671, HECTD4 rs2074356, and CETP rs2303790 were SNPs associated for HDL-C variability. APOA5 rs662799 passed Bonferroni correction with p-value of 1.789 × 10−9. Among the SNPs associated with cholesterol variability, rs80056520 and rs2266788 variants were associated with CACS ≥400 and coronary stenosis ≥70% and rs662799 variant was associated with coronary stenosis ≥70%.ConclusionTwo SNPs associated with LDL-C variability (APOA5 rs662799 and rs2266788) and one SNP associated with HDL-C variability (PXDNL rs80056520) were significantly associated with advanced coronary artery stenosis. Combining GWAS results with imaging parameters, our study may provide a deeper understanding of underlying pathogenic basis of the link between lipid variability and coronary atherosclerosis.

Association of adiposity evaluated by anthropometric, BIA, and DXA measures with cardiometabolic risk factors in nonobese postmenopausal women: the CoLaus/OsteoLaus cohort.

After menopause, body composition changes with body fat accumulation, and an increase in cardiometabolic risk factors. Total fat mass, regional fat mass, and visceral adipose tissue (VAT) may be estimated with anthropometric measures, bioelectrical impedance analysis (BIA), and dual-energy X-ray absorptiometry (DXA). The aim of our study was to assess which measurement correlated best with cardiometabolic risk factors in healthy nonobese postmenopausal women. The CoLaus/OsteoLaus cohort included 1,500 postmenopausal women (age range 50-80). We analyzed correlations between: 1) measurements of body composition assessed by anthropometric measures, BIA, and DXA and 2) these measurements and different selected cardiometabolic risk factors, such as blood pressure, lipid markers (cholesterol subtypes and triglycerides), and metabolic markers (glucose, insulin, adiponectin, and leptin). Spearman correlation coefficient, stepwise forward regression, and linear regression analyses were used to determine association between anthropometric measurements and cardiometabolic risk factors. In the 803 included participants (mean age 62.0 ± 7.1 y, mean body mass index 25.6 kg/m2 ± 4.4), correlations between total fat mass measured by BIA and total fat mass, android fat, gynoid fat, or VAT measured by DXA are very strong (from r = 0.531, [99% confidence interval (CI), 0.443-0.610] to r = 0.704, [99% CI, 0.640-0.758]). Body mass index and waist circumference have a higher correlation with VAT (r = 0.815, [99% CI, 0.772-0.851] and r = 0.823 [99% CI, 0.782-0.858], respectively) than BIA (r = 0.672 [99% CI, 0.603-0.731]). Among the anthropometric measurement and the measurements derived from DXA and BIA, VAT is the parameter most strongly associated with cardiometabolic risk factors. VAT better explains the variation of most of the cardiometabolic risk factors than age and treatment. For example, nearly 5% of the variability of the diastolic blood pressure (9.9 vs 4.9), nearly 15% of the variability of high-density lipoprotein cholesterol (20.3 vs 3.8) and triglyceride (21.1 vs 6.5), 25.3% of the variability of insulin (33.3 vs 8.1), and 37.5% of the variability of leptin (37.7 vs 1.1) were explained by VAT. BIA seems not to be a good tool to assess VAT. At the population level, waist circumference and body mass index seem to be good tools to estimate VAT. VAT measured by DXA is the parameter most correlated with cardiometabolic risk factors and could become a component of the cardiometabolic marker on its own.

Effect of blood lipid variability on mortality in patients with type 2 diabetes: a large single-center cohort study

BackgroundDyslipidemia is a major cardiovascular risk factor and common in diabetes patients. Most guidelines focus on optimal lipid levels, while variation of lipid profiles is far less discussed. This study aims to investigate the association of visit-to-visit variability in blood lipids with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes.MethodsWe identified 10,583 type 2 diabetes patients aged ≥ 30 years with follow-up ≥ 3 years and who participated in the Diabetes Care Management Program at a medical center in Taiwan. Variability in lipid profiles within 3 years after entry was calculated using coefficient of variation. Cox proportional hazard models were used to evaluate lipid variability in relation to subsequent mortality.ResultsOver a mean follow-up of 6.4 years, 1838 all-cause deaths (809 cardiovascular deaths) were observed. For each 10% increase in variability in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol, the hazard ratios (95% confidence intervals) of all-cause mortality were 1.30 (1.22–1.37), 1.05 (1.01–1.09), and 1.10 (1.03–1.16), respectively; those of cardiovascular mortality were 1.27 (1.16–1.39), 1.08 (1.02–1.15), and 1.16 (1.07–1.27), respectively. Each 10% increase in high-density lipoprotein cholesterol variability conveyed 31% greater risk of non-cardiovascular mortality. High variability in total cholesterol and low-density lipoprotein cholesterol increased all-cause mortality in subgroups of nonsmoking, regular exercising, non-dyslipidemia, and more severe status of diabetes at baseline.ConclusionsBlood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.

Abstract P102: Variability In Lipid Levels And Risk For Cardiovascular Disease: An Electronic Health Record-based Population Cohort Study

Background: Larger within-patient variability of lipid levels has been associated with an increased risk of cardiovascular disease (CVD). However, measures of lipid variability are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record (EHR)-based population cohort and assessed associations with incident CVD. Methods: We identified all individuals ≥40 years of age who resided in Olmsted County, MN on 1/1/2006 (index date) without prior CVD. CVD was defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention or stroke. Patients with ≥3 measurements of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides during the 5 years before the index date were retained in the analyses. Lipid variability was calculated using variability independent of the mean (VIM). Patients were followed through 9/30/2017 for incident CVD (including CVD death). Cox regression was used to investigate the association between quintiles of lipid VIMs and incident CVD. Results: We identified 18,642 individuals (mean age 60; 55% female) who were free of CVD at baseline and VIM calculated for at least one lipid measurement. After adjustment, those in the highest VIM quintiles of total cholesterol had a 25% increased risk of CVD (Q5 vs. Q1 HR: 1.25, 95% CI: 1.08-1.45; Table). We observed similar results for LDL-C (Q5 vs. Q1 HR: 1.20, 95% CI: 1.04-1.39) and HDL-C (Q5 vs. Q1 HR: 1.25, 95% CI: 1.09-1.43). There was no association between triglyceride variability quintiles and CVD risk. Conclusion: In a large EHR-based population cohort, high variability in total cholesterol, HDL-C and LDL-C was associated with an increased risk of CVD, independently of traditional risk factors, suggesting it may be a target for intervention. Lipid variability can be calculated in the EHR environment but more research is needed to determine its clinical utility.

Association of High-Density Lipoprotein Cholesterol Variability and the Risk of Developing Parkinson Disease.

To investigate the longitudinal association among high-density lipoprotein cholesterol (HDL-C) level, HDL-C variability, and the risk of developing Parkinson disease (PD). We conducted a nationwide, population-based cohort study. We included 382,391 patients aged ≥65 years who underwent at least 3 health examinations provided by the Korean National Health Insurance System from 2008 to 2013 and followed up until 2017. Individuals with a history of PD and missing values were excluded (n = 1,987). We assessed HDL-C variability using 3 indices, including variability independent of the mean (VIM). A multivariate-adjusted Cox proportional hazards regression analysis was performed. Among the 380,404 participants, 2,733 individuals were newly diagnosed with PD during a median follow-up period of 5 years. The lowest quartile (Q1) group of baseline HDL-C and mean HDL-C was associated with increased PD incidence as compared with the highest quartile (Q4) group (adjusted hazard ratio [aHR], 1.20; 95% confidence interval [CI], 1.08-1.34; and aHR, 1.16; 95% CI, 1.04-1.30, respectively). The Q4 group of HDL-C variability (VIM) was associated with increased PD incidence compared to the Q1 group (aHR, 1.19; 95% CI, 1.06-1.33). The group with the Q1 of baseline HDL-C and with the Q4 of HDL-C variability had the highest risk of PD incidence (aHR, 1.6; 95% CI, 1.31-1.96). Lower HDL-C level and greater HDL-C variability were associated with a higher incidence of PD.

Lipid Level, Lipid Variability, and Risk of Multiple Myeloma: A Nationwide Population-Based Study of 3,527,776 Subjects.

Simple SummaryThere is preclinical evidence that abnormalities in lipid metabolism promote cancer development, and a few studies show the association between lipid levels and multiple myeloma (MM). However, to our knowledge, the role of lipid variability as a risk factor for MM has not been evaluated. We investigated whether lipid level and its variability are associated with the development of MM at a population level. Lower baseline lipid levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, and high variability in high-density lipoprotein cholesterol were all associated with increased risk of developing MM. These findings support the role of lipid metabolism in MM risk.(1) Background: There is evidence that abnormality in lipid metabolism promotes cancer development. This study investigated whether lipid level and its variability are associated with the development of MM at a population level. (2) Methods: A retrospective cohort study included a total of 3,527,776 subjects aged 40 and above who participated in ≥3 health examinations within the previous five years, including the index year (2012–2013). Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were measured, and visit-to-visit lipid variability were calculated by variability independent of the mean (VIM) method. The study population was followed from the health examination date in the index year until the diagnosis of MM, death, or the last follow-up date (31 December 2017). (3) Results: During a median (5–95%) 5.1 years of follow-up, 969 subjects developed MM. A lower risk of MM was observed with higher quartiles of baseline lipid levels compared to the lowest quartile group (Q4 vs. Q1: adjusted hazard ratios (aHRs) 0.51, 95% confidence interval (CI) (0.42–0.61) for TC; 0.50 (0.41–0.61) for HDL-C; 0.65 (0.54–0.77) for LDL-C; and 0.72 (0.60–0.87) for TG in model (3). Among all lipid measures, only variability in HDL-C was associated with risk of MM: aHRs (95% CI) were 1.12 (0.91–1.38), 1.19 (0.97–1.46), and 1.34 (1.09–1.65) in the Q2, Q3, and Q4, respectively, compared to the Q1 of VIM of HDL-C. (4) Conclusions: This study shows that patients with lower lipid levels and high HDL-C variability are at increased risk of developing MM.

Visit-to-visit variability of lipid measurements and the risk of myocardial infarction and all-cause mortality: A prospective cohort study

Background and aimsPrevious studies suggested that increased visit-to-visit variability in lipid measurements is associated with cardiovascular disease in specific or high-risk populations. Because it is unknown whether this notion applies to the general population, we investigated whether lipid variability has additive effects on the risk of all-cause mortality and myocardial infarction (MI) in the general population. MethodsWe identified 51,620 subjects from the Kailuan cohort who had no history of MI, stroke and cancer and who underwent ≥3 health examinations from 2006 to 2010. Variability in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) measurements was measured using the coefficient of variation (CV), standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Cox proportional hazards models were used to calculate the hazard ratios (HRs). ResultsDuring a median of 7.03 years of follow-up, 426 (1.21) incidents of MI and 2243 (6.45) incidents of all-cause mortality occurred. In the multivariable-adjusted model, the HRs comparing participants in the highest versus lowest quartile of the CV for HDL-C were 1.56 (95% CI, 1.17–2.08; p for trend<0.01) for MI and 1.22 (95% CI, 1.09–1.37; p for trend<0.01) for all-cause mortality. For the highest quartile compared with the lowest quartile of LDL-C variability, the risk of MI and all-cause mortality increased by 34% (HR, 1.34; 95% CI, 1.03–1.82; p for trend<0.05) and 19% (HR, 1.19; 95% CI, 1.04–1.36; p for trend<0.05), respectively. We did not observe any significant association between TG variability and MI or all-cause mortality. ConclusionsThese findings suggest that high visit-to-visit HDL-C and LDL-C variability is associated with an increased incidence of MI and all-cause mortality in a Chinese community population.

Variability in blood lipids affects the neutrophil to lymphocyte ratio in patients undergoing elective percutaneous coronary intervention: a retrospective study

BackgroundAtherosclerosis is associated with chronic inflammation and lipid metabolism. The neutrophil to lymphocyte ratio (NLR) as an indicator of inflammation has been confirmed to be associated with cardiovascular disease prognosis. However, few studies have explored the effects of blood lipid variability on NLR. The aim of this study was to explore the relationship between variability in blood lipid levels and NLR.MethodsThe association between variability in blood lipids and NLR was assessed with both univariate and multivariate linear regression. Multivariate linear regression was also performed for a subgroup analysis.ResultsThe variability of high-density lipoprotein cholesterol (HDL-C) (regression coefficients [β] 4.008, standard error (SE) 0.503, P-value< 0.001) and low-density lipoprotein cholesterol (LDL-C) ([β] 0.626, SE 0.164, P-value< 0.001) were risk factors for the NLR value, although baseline LDL-C and HDL-C were not risk factors for NLR values. Variability of HDL-C ([β] 4.328, SE 0.578, P-value< 0.001) and LDL-C ([β] 0.660, SE 0.183, P-value< 0.001) were risk factors for NLR variability. Subgroup analysis demonstrated that the relationship between variability of LDL-C and NLR was consistent with the trend of the total sample for those with diabetes mellitus, controlled blood lipid, statins, atorvastatin. The relationship between the variability of HDL-C and NLR was consistent with the trend of the total sample in all subgroups.ConclusionThe variability of HDL-C and LDL-C are risk factors for the value and variability of NLR, while the relationship between variability of HDL-C and NLR is more stable than the variability of LDL-C in the subgroup analysis, which provides a new perspective for controlling inflammation in patients undergoing PCI.

Association of High-Density Lipoprotein Cholesterol With Cognitive Function: Findings From the PROspective Study of Pravastatin in the Elderly at Risk.

Objective: We aimed to examine whether variability in high-density lipoprotein cholesterol (HDL-c) over time was associated with cognitive function. Method: We conducted a post hoc analysis of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. Our sample included 4,428 participants with at least two repeated HDL-c measures between Months 3 and 24 postbaseline and with cognitive assessments at Month 30. HDL-c variability was defined as the intraindividual standard deviation over each person's repeated measurements. Results: Higher HDL-c variability was associated with worse performance on the Letter-Digit Coding Test (β [95% confidence interval] [CI] = -4.39 [-7.36, -1.43], p = .004), immediate recall on the 15-Picture Learning Test (β [95% CI] = -0.98 [-1.86, -0.11], p = .027), and delayed recall on the 15-Picture Learning Test (β [95% CI] = -1.90 [-3.14, -0.67], p = .002). The associations did not vary by treatment group. Discussion: Our findings suggest that variability in HDL-c may be associated with poor cognitive function among older adults.

Visit-to-Visit Variability of Lipids Measurements and the Risk of Stroke and Stroke Types: A Prospective Cohort Study.

Background and PurposePrevious studies suggested increased visit-to-visit variability of total cholesterol (TC) is associated with stroke. This study aimed to investigate the associations of various lipids measurements variability and the risk of stroke and stroke type (ischemic and hemorrhagic stroke). MethodsFifty-one thousand six hundred twenty participants in the Kailuan Study without history of myocardial infarction, stroke, and cancer who underwent three health examinations during 2006 to 2010 were followed for incident stroke. Variability in TC, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) measurements were measured using the coefficient of variation (CV), standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). ResultsDuring a median of 6.04 years of follow-up, 1,189 incident stroke (1,036 ischemic and 160 hemorrhagic stroke) occurred. In the multivariable-adjusted model, the hazard ratio (HR) comparing participants in the highest versus lowest quartile of CV of HDL-C were 1.21 (95% confidence interval [CI], 1.02 to 1.45; P for trend=0.013) for ischemic stroke. The highest quartile of CV of LDL-C was associated with 2.17-fold risk of hemorrhagic stroke (HR, 2.17; 95% CI, 1.25 to 3.75; P for trend=0.002) compared with the lowest quartile. We did not observe any significant association between TC and triglycerides variability with any of stroke. Consistent results were obtained when calculating variability index using SD, VIM, or ARV. ConclusionsThese findings suggest the high visit-to-visit HDL-C and LDL-C variability were associated with an increased incidence of ischemic and hemorrhagic stroke, respectively.

P1884Low lipid levels and high variability correlate with the risk of new-onset atrial fibrillation

Abstract Background High levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease. We investigated their roles in the development of atrial fibrillation (AF). This is the largest cohort study yet on the association between lipid levels and AF, and the first study on the association between lipid variability and AF. Methods A nationwide population-based cohort of 3,828,652 adults (mean age 43.9 years) from the Korean National Health Insurance Service database without prevalent AF, not on lipid-lowering medication, and with at least 3 measurements of each lipid parameter at 1–2 year intervals over a 4-year period were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured, and lipid variability was calculated using variability independent of mean. The cohort was divided into quartiles by baseline lipid levels and lipid variability, and followed up for incident AF. Results During median 3.4 years of follow-up, AF was newly diagnosed in 13,240 (0.35%). AF development was inversely associated with TC and LDL-C levels (for top vs. bottom quartile; TC, hazard ratio [HR] 0.76, 95% confidence interval [95% CI] 0.72–0.80); LDL-C, HR 0.78, 95% CI 0.74–0.82) in both sexes, and with TG levels in men (HR 0.85, 95% CI 0.80–0.90). Meanwhile, AF development was associated with higher LDL-C and HDL-C variability (for top vs. bottom quartile; LDL-C, HR 1.16, 95% CI 1.10–1.22; HDL-C, HR 1.08, 95% CI 1.03–1.14) in both sexes, and with TC variability in men (HR 1.16, 95% CI 1.10–1.22). Conclusions Lower cholesterol levels (TC, LDL-C) and higher cholesterol variability (LDL-C, HDL-C) were associated with higher risk for AF. Low TG levels and high TC variability were also associated with AF incidence in men. These findings support the “cholesterol paradox” in AF, and suggest that cholesterol variability is also a risk factor for AF development.

HDL-Cholesterol, Its Variability, and the Risk of Diabetes: A Nationwide Population-Based Study.

The bidirectional relationship between low high-density lipoprotein cholesterol (HDL-C) and glucose intolerance is well established. Recent studies suggested an association of lipid variability with various health outcomes. To investigate the combined effect of HDL-C levels and their variability on the risk of diabetes. A population-based cohort study. In all, 5,114,735 adults without known diabetes in the Korean National Health Insurance System cohort who underwent three or more health examinations from 2009 to 2013 were included. Visit-to-visit HDL-C variability was calculated using variability independent of the mean (VIM) and the coefficient of variation (CV). Low mean and high variability groups were defined as the lowest and highest quartiles of HDL-C mean and variability, respectively. Newly developed diabetes. There were 122,192 cases (2.4%) of incident diabetes during the median follow-up of 5.1 years. Lower mean or higher variability of HDL-C was associated with higher risk of diabetes in a stepwise manner, and an additive effect of the two measures was noted. In the multivariable-adjusted model, the hazard ratios and 95% CIs for incident diabetes were 1.20 (1.18 to 1.22) in the high mean/high VIM group, 1.35 (1.33 to 1.37) in the low mean/low VIM group, and 1.40 (1.38 to 1.42) in the low mean/high VIM group compared with the high mean/low VIM group. Similar results were observed when modeling the variability using CV and in various subgroup analyses. Low mean and high variability in HDL-C were independent predictors of diabetes with an additive effect. Both elevating and stabilizing HDL-C may be important goals for reducing diabetes risk.

Intra-individual variability in high density lipoprotein cholesterol and risk of end-stage renal disease: A nationwide population-based study

Background and aimsThere is a growing evidence demonstrating an association between dyslipidemia and progression of chronic kidney disease (CKD), but results on the effects of high-density lipoprotein cholesterol (HDL-C) on renal outcome have been conflicting. In this study, the relationship between HDL-C variability and the risk for progression to end-stage renal disease (ESRD) was investigated. MethodsThis study analyzed data of 4,283,318 subjects who were free of ESRD at the time of enrollment, received more than three medical examinations from 2009 to 2012, and were followed to the end of 2015, based on the Korean National Health Insurance Service database. HDL-C variability was measured using the standard deviation, coefficient of variation, average real variability and variability independent of the mean (VIM). ResultsA total of 2,095 new cases of ESRD were observed during a median follow up of 3.38 years. There was a graded association between higher HDL-C variability and incident ESRD. In the multivariable adjusted model, hazard ratio comparing the highest and lowest quartiles of VIM of HDL-C was 1.82 (95% confidence interval, 1.58–2.09). The results were consistent when the variability of HDL-C was modeled using standard deviation, coefficient of variation and average real variability and were independent of other confounding factors, including the presence of CKD. ConclusionsHDL-C variability independently predicted an increased risk for developing ESRD. Our findings suggest that identification of HDL-C variability may help improve risk stratification for the prevention of ESRD.

Effect of visit-to-visit LDL-, HDL-, and non-HDL-cholesterol variability on mortality and cardiovascular outcomes after percutaneous coronary intervention

Background and aimsVisit-to-visit variability in biological measures has been suggested as an independent predictor of cardiovascular disease (CVD). Although low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) are important risk factors of CVD, there are few studies investigating the effect of variability in LDL-C and HDL-C on cardiovascular outcomes. We investigated the association between visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C and major adverse cardiovascular and cerebrovascular events (MACCE) in patients who underwent percutaneous coronary intervention (PCI). MethodsData from 1792 subjects who underwent PCI from January 2004 to December 2009 were analyzed. Visit-to-visit variability was calculated using various indices: standard deviation (SD), coefficient of variation, and corrected variability independent of mean (cVIM). MACCE comprised all-cause death, non-fatal myocardial infarction, and stroke. ResultsDuring a median follow-up period of 65 months, 114 subjects (6.4%) experienced MACCE: 68 (3.8%) all-cause death; 43 (2.4%) stroke, and 15 (0.8%) non-fatal myocardial infarction. Visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C was significantly higher in the MACCE group compared to the non-MACCE group. In multiple regression analysis, all LDL-C, HDL-C, and non-HDL-C variability parameters were independent predictors for MACCE after adjusting for potential confounding factors. Each 1-SD increase of cVIM in LDL-C, HDL-C, and non-HDL-C increased the risk of MACCE by 34% (HR 1.34 [95% CI, 1.18–1.52]), 50% (HR 1.50 [95% CI 1.32–1.71]), and 37% (HR 1.37 [95% CI, 1.20–1.57]), respectively. These relationships were observed in various subgroups according to age, sex, and diabetes status. ConclusionsVisit-to-visit variability in LDL-C, HDL-C, and non-HDL-C is associated with MACCE in subjects with previous PCI.

Visit-to-visit variability of lipid measurements as predictors of cardiovascular events

Higher visit-to-visit variability in risk factors such as blood pressure and low-density lipoprotein (LDL)-cholesterol are associated with an increase in cardiovascular (CV) events. The purpose of this study was to determine whether variability in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels predicted coronary and CV events in a clinical trial population with known coronary disease. We assessed intraindividual variability in fasting high-density lipoprotein (HDL)-cholesterol, triglyceride, and LDL-cholesterol measurements among 9572 patients in the Treating to New Targets trial and correlated the results with coronary events over a median follow-up of 4.9years. In the fully adjusted Cox model, 1 standard deviation of average successive variability, defined as the average absolute difference between successive values, was associated with an increased risk of a coronary event for HDL-cholesterol (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.11-1.21, P<.0001), for triglycerides (HR 1.09, 95% CI 1.04-1.15, P=.0005), and for LDL-cholesterol (HR 1.14, 95% CI 1.09-1.19, P<.0001). Similar results were found for the 3 other measures of variability, standard deviation, coefficient of variability, and variability independent of the mean. Similar results were seen for CV events, stroke, and nonfatal myocardial infarction. Higher variability in triglyceride and LDL-cholesterol, but not HDL-cholesterol, was predictive of incident diabetes. The correlation among the variability of the 3 lipid measurements was weak. Visit-to-visit variability in fasting measurements of HDL-cholesterol, triglycerides, and LDL-cholesterol are predictive of coronary events, CV events, and for triglyceride and low-density lipoprotein cholesterol variability, incident diabetes. The mechanisms accounting for these associations remain to be determined.

Visit-to-visit variability in LDL- and HDL-cholesterol is associated with adverse events after ST-segment elevation myocardial infarction: A 5-year follow-up study

IntroductionWe evaluated the relationship between visit-to-visit low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) variability and 5-year clinical outcomes in patients who presented with ST-segment elevation myocardial infarction (STEMI). Methods130 patients presenting with STEMI and surviving to discharge were analyzed. Visit-to-visit LDL-C and HDL-C variability was evaluated from 2 months after discharge on the basis of corrected variation independent of mean (cVIM, primary measure), coefficient of variation and standard deviation. Major adverse cardiac event (MACE) included death, myocardial infarction, stroke, unplanned revascularization, and heart failure admission. ResultsAfter an average of 62.4 ± 30.5 months follow-up, 41 patients (31.5%) had experienced MACE. Compared with the non-MACE group, the MACE group had a higher visit-to-visit LDL-C variability (cVIM: 0.23 ± 0.11 vs. 0.19 ± 0.08; p = 0.049; coefficient of variation: 0.24 ± 0.12 vs. 0.19 ± 0.00; p = 0.019; standard deviation: 24.1 ± 14.5 vs. 17.6 ± 10.0; p = 0.006), mean follow-up LDL-C (p = 0.033) and a higher prevalence of diabetes mellitus (p = 0.012). After adjusting for mean follow-up cholesterol levels and diabetes mellitus, each 0.01 cVIM increase in LDL-C and HDL-C variability increased the risk of MACE by 3.4% (HR: 1.034; 95% CI: 1.004 to 1.065; p = 0.025) and 6.8% (HR: 1.068; 95% CI: 1.003 to 1.137; p = 0.04), respectively. Results derived from coefficient of variation and standard deviation as measures of cholesterol variability were similar. ConclusionThis is the first report to show an independent association between visit-to-visit LDL-C and HDL-C variability and long-term MACE in patients presenting with STEMI.