Total Cholesterol Variability Research Articles

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.

Hubungan Kadar Hba1c dan Kolesterol Total dengan Kejadian Peripheral Arterial Disease pada Pasien Diabetes Mellitus Tipe 2

Type 2 diabetes mellitus (DMT2) is caused by the inability of pancreatic beta cells to produce insulin and tissue resistance to insulin. T2DM requires ongoing treatment to control blood sugar and prevent complications such as Peripheral Arterial Disease (PAD) and high cholesterol problems. HbA1c measurement and total cholesterol monitoring are important in diabetes management and prevention of serious complications. An observational analytical study, cross-sectional approach was conducted in September 2022 at Gatak Health Center, Sukoharjo on 65 patients with T2DM. The data were analyzed with a 2x2 chi square test table. The results of the study found that 21 (32.3%) research subjects experienced PAD. Bivariate test between total cholesterol and Hba1c with consecutive PAD incidence p = 0.377; p = 0.416. It can be concluded that there is no significant relationship between the variables total cholesterol and Hba1c with the incidence of PAD. This can be caused by lack of control over other risk factors for PAD events such as smoking, hypertension, duration of diabetes, age, and gender.
 

Effect of cholesterol variability on the incidence of cataract, dementia, and osteoporosis: A study using a common data model.

The effects of cholesterol variability on cataracts, dementia, and osteoporosis remain controversial. Using a common data model, we investigated the effects of variations in cholesterol levels on the development of cataracts, dementia, and osteoporosis. Patients who received statin therapy between 2011 and 2020 and those with 3 or more tests for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels were included. The patients were divided into those with a coefficient of variation (CV) of TC higher than the mean (high-CV group) and those with a lower CV of TC (low-CV group). Moreover, 1:1 propensity score matching was conducted based on demographic variables. Cataract, dementia, or osteoporosis was defined as having a diagnostic, drug, or surgical code based on the cohort definition. Of the 12,882 patients, cataracts, dementia, and osteoporosis were developed in 525 (4.1%), 198 (1.5%), and 438 (3.4%) patients, respectively. The stratified Cox proportional hazards model showed that the incidences of cataracts and osteoporosis were 1.38 and 1.45 times greater in the high-CV group than in the low-CV group, respectively. Our study revealed that TC variability is associated with developing cataracts and osteoporosis.

Association between lipid variability and the risk of mortality in cancer patients not receiving lipid-lowering agents.

We investigated the association between total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride (TG) variability and cancer patient mortality risk. We retrospectively analyzed 42,539 cancer patients who were not receiving lipid-lowering agents and who had at least three TC measurements within 2 years of their initial cancer diagnosis. Using a multivariable Cox regression model, the risk of mortality was evaluated. In multivariable analysis, Q2 (adjusted hazard ratio [aHR]: 1.32, 95% confidence interval (CI): 1.24-1.41), Q3 (aHR: 1.66, 95% CI: 1.56-1.76), and Q4 (aHR: 1.96, 95% CI: 1.84-2.08) of coefficient of variation (CV) in TC were significantly associated with mortality risk compared to Q1, showing a linear association between higher TC variability and mortality (P for trend<0.001). Q2 (aHR: 1.34, 95% CI: 1.06-1.77), Q3 (aHR: 1.40, 95% CI: 1.06-1.85), and Q4 (aHR: 1.50, 95% CI: 1.14-1.97) were all significantly associated with a higher risk of death compared to Q1 in multivariable Cox regression for the association between CV in LDL and all-cause mortality (P for trend=0.005). In cancer patients who do not receive lipid-lowering agents, high variability in total cholesterol and LDL cholesterol levels was found to pose significant role in mortality risk.

Association of total cholesterol variability with risk of venous thromboembolism: A nationwide cohort study.

The effects of total cholesterol (TC) on coagulation and hemostatic systems could contribute to the development of venous thromboembolism (VTE). We investigated this possible association using TC variability. From the Korean NHIS-HEALS database, 1,236,589 participants with health screenings between 2003 and 2008 were included. TC variability was assessed using various parameters, including the coefficient of variation (CV), standard deviation (SD), and variability independent of mean (VIM). Occurrence of VTE was established by identifying at least two medical claims with a diagnostic code including various types of VTE: deep vein thrombosis (DVT) (I80.2-80.3), pulmonary embolism (PE) (I26, I26.0, I26.9), intraabdominal VTE (I81, I82, I82.2-82.3), and other VTE (I82.8-82.9). Throughout the study's median follow-up period of 12.4 years (interquartile range 12.2-12.6) years, TC levels were assessed a total of 5,702,800 times. VTE occurred in 11,769 (1.08%) patients (DVT (4,708 (0.43%)), PE (3,109 (0.29%)), intraabdominal VTE (5,215 (0.48%)), and other VTE (4,794, (0.44%)). As a result, there was gradual association was observed between higher TC variability and occurrence of VTE. Multivariable analysis showed that quartile of TC variability using CV showed a positive correlation with the occurrence of VTE (adjusted hazard ratio (the highest versus lowest quartile), 1.14, 95% confidence interval, 1.08-1.20, p < 0.001). This result remained consistent applying to SD and VIM. In addition, higher quartile of TC variability was consistently associated with the development of various types of VTE in subgroup analysis. Increased TC variability may be associated with increased VTE risk. This analysis highlights the importance of maintaining stable TC levels to prevent the development of VTE.

1432-P: Lipid Profile and Visit-to-Visit Variability of LDL Cholesterol, the Association with Risk of Young-Onset Type 2 Diabetes—Nationwide Retrospective Cohort Study

Background: It is reported that the prevalence of young-onset type 2 diabetes (YOD) is increasing in recent. YOD usually defined that it diagnosis at age &amp;lt;40 year. However, the underlying pathophysiology of YOD is still unknown. Previous studies suggested that lipid level and its variability associated with various health outcome. Aim: We aimed to examine the effect of lipid profile and variability of low-density lipoprotein cholesterol (LDL-C) on the risk of young-onset type 2 diabetes in Participants with 20 to 40 Years Methods: We examined the General Health Check-up sub-dataset of the Korean National Health Insurance Service (NHIS) of 1,376,416 participants with 20 to 40 year who had at least three health check-ups between 2012 and 2017, and were not reported to have diabetes during that time. The visit to visit variability of LDL-C was measured using variability independent of the mean (VIM), standard deviation (SD), average successive variability (ASV), and coefficient of variation (CV),. Results: During a median of 5 years of follow up, 19,706 subjects (1.5%) developed YOD. Risk of incident YOD increased with quartiles 2, 3 and 4 versus quartile 1 in Total cholesterol (TC), LDL-C, triglyceride (TC) whereas, inversely associated with high density lipoprotein cholesterol (HDL-C) in multivariate analysis. Compare with the lowest quartile, the highest quartile of VIM, SD, ASV and CV of LDL-C was associated with 1.22-1.43 fold risk of YOD (VIM HR, 1.292; SD HR 1.428; ASV HR 1.364; CV HR 1.218, P for trend &amp;lt;0.0001) in the multivariable adjusted model. When calculating variability of TC, LDL and HDL-C index, we did not observe that consistent results were obtained. Conclusion: Risk of incident YOD is increased with increasing lipid profile. High visit to visit LDL-C variability and level of LDL-C per se, were independent predictors of YOD. Both lowering and stabilizing LDL-C can be beneficial for reducing diabetes risk in young population. Disclosure M.Seo: None. S.Park: None. E.Rhee: None. W.Lee: None.

Total Cholesterol Variability and the Risk of Osteoporotic Fractures: A Nationwide Population-Based Cohort Study.

Several risk factors for osteoporotic fractures have been identified but reports of the association of lipid parameters with the occurrence of osteoporotic fractures have been limited. We aimed to examine whether serum total cholesterol (TC) variability is associated with osteoporotic fractures. The study included 3,00,326 subjects who had undergone three or more health examinations between 2003 and 2008. The primary endpoint was the incidence of osteoporotic fractures, including vertebral, hip, distal radius, and humerus fractures. TC variability was evaluated based on the following three parameters: coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). A total of 29,044 osteoporotic fracture events (9.67%) were identified during a median of 11.6 years of follow-up. The risk of osteoporotic fractures in the highest quartile was significantly higher compared with the lowest quartile according to the three indices of TC variability with adjusted hazard ratios (HR) and 95% confidence intervals (CI) as follows: CV (HR 1.11, 95% CI [1.08-1.15]), SD (HR 1.07, 95% CI [1.04-1.11]) and VIM (HR 1.07, 95% CI [1.04-1.11]). The Kaplan-Meier curves showed a significantly positive relationship between the higher quartile of TC variability and overall osteoporotic fractures. The association remained significant in subgroup analyses of vertebral and hip fractures, regardless of the indices of TC variability. Our study showed that visit-to-visit TC variability was found to be associated with osteoporotic fracture risk. Maintaining TC levels stable may help attenuate the osteoporotic fracture risk in the future.

Relationship between Angiotensin II, Vascular Endothelial Growth Factor, and Arteriosclerosis Obliterans.

To investigate the relationship between angiotensin II (Ang II), vascular endothelial growth factor (VEGF), and arteriosclerosis obliterans (ASO). 60 ASO patients diagnosed and treated from October 2019 to December 2021 were selected for the observation group while 30 healthy physical examiners were for the control group. The general information (gender, age, history of smoking, diabetes, and hypertension) and arterial blood pressure (systolic and diastolic blood pressure) of the two groups were collected, and parameters like disease site and duration, Fontaine stage, and ankle-brachial index (ABI) of ASO patients have been evaluated. Ang II, VEGF, uric acid (UA), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC) were also detected for the two groups. The variations in UA, LDL, HDL, TG, and TC among two groups along with levels of Ang II and VEGF in ASO patients in accordance to conditions like the general situation, disease duration, disease site, Fontaine stage, and ABI risk level have been studied to establish a correlation between Ang II and VEGF and ASO. (1) The proportion of males with a history of smoking, diabetes, and hypertension was higher (P < 0.05) among ASO patients in comparison to the control group. The diastolic blood pressure, LDL, TC, Ang II, and VEGF levels were found to be higher (P < 0.05) whereas HDL was low (P < 0.01). (2) The level of Ang II in male patients with ASO was significantly higher than that in female ASO patients (P < 0.05). In ASO patients, the levels of Ang II and VEGF increased not only with age (P < 0.01) but also with progression in Fontaine stages II, III, and IV (P < 0.01). (3) Logistic regression analysis revealed Ang II and VEGF as risk factors for ASO. (4) An AUC (area under the ROC (receiver operator characteristic) curve) for Ang II and VEGF for the diagnosis of ASO was 0.764 (good) and 0.854 (very good), respectively, while their combined AUC in diagnosing ASO was 0.901 (excellent). The AUC of Ang II and VEGF together in diagnosing ASO was greater than that of Ang II and VEGF alone along with higher specificity as well (all P < 0.05). Ang II and VEGF were correlated with the occurrence and development of ASO. The AUC analysis demonstrates that Ang II and VEGF were highly discriminative of ASO.

THE HDL LEVEL IN DIABETIC FOOT ULCER PATIENTS WITH AND WITHOUT AMPUTATION AT DR. SEOTOMO GENERAL ACADEMIC HOSPITAL SURABAYA

Highlights1. Diabetes mellitus is a category of metabolic disease characterized by uncontrolled hyperglycemia.2. This study revealed no statistically significant differences in total cholesterol, TG, LDL, HDL, or LDL/HDL ratio between amputated and non-amputated DFU patients. AbstractBackground: Diabetic foot ulcers (DFU) are microvascular and macrovascular consequences of diabetes and are associated with neuropathy, vascular disease, and immunosuppression. Increased blood glucose levels may result in the glycosylation of proteins in the nerve cells of the foot, leading to ischemia and cellular disturbances that can damage muscular, sensory, and autonomic neurons. Objective: To compare the lipid profiles of amputated and non-amputated DFU patients. Material and Method: This was a cross-sectional, analytic, retrospective research using total sample approach to analyze the medical records of all diabetes patients admitted to Dr. Soetomo General Academic Hospital between February 2018 and December 2020, with or without amputation. Result: The average age of DFU patients at Dr. Soetomo General Academic Hospital was 55.6 9.4 years, and the majority of patients were female (57%). Diabetic foot ulcers were most prevalent in the age group ≥50 years old (74%), amputated DFU patients had larger mean total cholesterol, TG, LDL, and HDL than non-amputated DFU patients, although the difference was not statistically significant. While the mean LDL/HDL ratio was greater in non-amputated DFU patients, the difference was statistically insignificant. The HDL level was low in 84% of amputated DFU patients, whereas in non-amputated DFU patients it was 81%. Conclusion: This research showed no significant variation in total cholesterol, TG, LDL, HDL, or the LDL/HDL ratio between amputated and non-amputated DFU patients. Most DFU patients with and without amputations had low HDL values.

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.

The Effect of Total Cholesterol Variability on Clinical Outcomes After Percutaneous Coronary Intervention.

AimExploring the risk factors of prognosis in patients undergoing percutaneous coronary intervention (PCI) is of great importance. Our aim of the study is to investigate the association between variability in total cholesterol (TC) level and major adverse cardiovascular and cerebrovascular events (MACCE) in patients after PCI.MethodsBetween April 2004 and December 2009, 909 patients who underwent primary PCI and with at least three TC values were included in the final study. TC variability was calculated using four indices: standard deviation (SD), coefficient of variation (CV), the average successive variability (ASV), variability independent of the mean (VIM). MACCE comprised all-cause mortality, non-fatal myocardial infarction (MI), unplanned revascularization, hospitalization for heart failure, and non-fatal stroke.ResultsThere were 394 cases of MACCE during the follow-up period. When the subjects were divided into quartile groups by CV of TC, high CV groups were associated with a higher hazard ratio of MACCE than for lower CV groups. In multivariable adjusted models, TC variability and MACCE remained correlated [HR (95% CI): Q2, 1.17 (0.86–1.58); Q3, 1.38 (1.03–1.85); Q4, 1.63 (1.22–2.17)]. Similar patterns of MACCE were noted by quartiles of SD, ASV, and VIM.ConclusionVisit-to-visit TC variability is positively correlated with MACCE in patients after PCI.

The association of blood lipid parameters variability with ischemic stroke in hypertensive patients

Background and aimsThe relationship between lipid variability and stroke among patients with hypertension were inconclusive. We aimed to investigate the association of lipid variability with ischemic stroke in hypertensive patients. Methods and resultsThis retrospective cohort study included 4995 individuals with hypertension between 2013 and 2015, and recorded their status of ischemic stroke until the end of 2018. The variability in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured using the standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM) and average absolute difference between successive values (ASV). Multivariate Cox proportional hazards models with hazard ratios (HRs) and 95% confidence interval (CI) were performed. There were 110 cases of ischemic stroke during a median follow up of 4.2 years. The multivariable adjusted HRs and 95% CIs comparing the highest versus the lowest quartiles of SD of TC, LDL-C, HDL-C and TG were 4.429 (95% CI: 2.292, 8.560), 2.140 (95% CI: 1.264, 3.621), 1.368 (95% CI: 0.793, 2.359) and 1.421 (95% CI: 0.800, 2.525), respectively. High variability in TC and LDL-C were associated with a higher risk for ischemic stroke. Similarly, the results were consistent when calculating variability of TC and LDL-C using CV, ASV and VIM, and in various subgroup analyses. ConclusionHigher variability of TC and LDL-C associated with the risk of ischemic stroke among hypertensive patients. These findings suggest reducing variability of lipid parameters may decrease adverse outcomes.

Higher visit-to-visit total cholesterol variability is associated with lower cognitive function among middle-aged and elderly Chinese men

To examine the prospective associations between total cholesterol (TC) variability and cognitive function in a large sample of Chinese participants aged 45 years and above. A total of 6,377 people who participated in the China Health and Retirement Longitudinal Study (CHARLS) were included. TC variability was defined as the intra-individual standard deviation over two blood tests in CHARLS 2011 and 2015 (Wave 1 and Wave 3). Cognitive function was assessed by a global cognition score, which included three tests: episodic memory, figure drawing and Telephone Interview of Cognitive Status (TICS). Multivariate linear regression models (MRLMs) and generalized estimating equation (GEE) were used to investigate associations between TC variability and cognitive scores. After adjusting for potential confounders, male participants with higher visit-to-visit TC variability showed lower global cognition scores (β = − 0.71, P < 0.001). After further adjustment for baseline cognition, the association remained statistically significant (β = − 0.68, P < 0.001). The domains with declines were focused on episodic memory (β = − 0.22, P = 0.026) and TICS (β = − 0.44, P = 0.004). However, these associations were not found in women (β = − 0.10, P = 0.623). For men, the rates of decline in global cognition increased by 0.14 (β = − 0.14, P = 0.009) units per year while TC variability increased by 1 mmol/L. For males, higher visit-to-visit TC variability correlated with lower cognitive function and an increased rate of decreases in memory. More attention should be paid to cognitive decline in males with high TC variability, and particularly, on decreases in memory, calculation, attention and orientation.

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.

Intra-individual variability of total cholesterol is associated with cardiovascular disease mortality: A cohort study

Background and aimsThe relationship between serum total cholesterol (TC) and mortality remains inconsistent. Additionally, intra-individual variability of cholesterol has been of increasing interest as a new indicator for health outcomes. We aimed to examine the association between TC and its variability and risk of mortality. Methods and resultsWe performed a retrospective cohort study with 122,645 individuals aged over 40 years in Ningbo, China. The intra-individual variability was calculated using four metrics including standard deviation, coefficient variation, variation independent of mean and average successive variability. Hazard ratios and 95% confidence intervals were estimated for the associations of baseline and variability in TC with risk of mortality by Cox proportional hazards regression models. During 591,585.3 person-years of follow-up, 4563 deaths (including 1365 from cardiovascular disease, 788 from stroke and 1514 from cancer) occurred. A U-shaped association was observed for baseline TC level and risk of total, cardiovascular and cancer mortality, with lowest mortality at 5.46 mmol/L, 5.04 mmol/L and 5.51 mmol/L, respectively. As compared with subjects with TC variability in the lowest quartile, individuals in the highest quartile had 21% higher risk of all-cause mortality (HR = 1.21, 95% CI: 1.05 to 1.40), and 41% higher risk of CVD mortality (HR = 1.41, 95%CI: 1.10 to 1.81). ConclusionBoth too low and too high baseline TC level were associated with higher risk of total, cardiovascular disease and cancer mortality. Variability of TC could be a risk factor of total and CVD mortality, independent of mean TC level. Future studies are needed to confirm these findings.

Effects of Variability in Blood Pressure, Glucose, and Cholesterol Concentrations, and Body Mass Index on End-Stage Renal Disease in the General Population of Korea.

Aim: Metabolic parameters, such as blood pressure, glucose, lipid levels, and body weight, can interact with each other, and this clustering of metabolic risk factors is related to the progression to end-stage renal disease (ESRD). The effect of variability in metabolic parameters on the risk of ESRD has not been studied previously. Methods: Using nationally representative data from the Korean National Health Insurance System, 8,199,135 participants who had undergone three or more health examinations between 2005 and 2012 were included in this analysis. Intraindividual variability in systolic blood pressure (SBP), fasting blood glucose (FBG), total cholesterol (TC), and body mass index (BMI) was assessed by examining the coefficient of variation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability and low variability was defined as the lower three quartiles of variability. Results: Over a median (5–95%) of 7.1 (6.5–7.5) years of follow-up after the variability assessment period, 13,600 (1.7/1000 person-years) participants developed ESRD. For each metabolic parameter, an incrementally higher risk of ESRD was observed for higher variability quartiles compared with the lowest quartile. The risk of ESRD was 46% higher in the highest quartile of SBP variability, 47% higher in the highest quartile of FBG variability, 56% higher in the highest quartile of BMI variability, and 108% higher in the highest quartile of TC variability. Compared with the group with low variability for all four parameters, the group with high variability for all four parameters had a significantly higher risk for incident ESRD (hazard ratio (HR) 4.12; 95% CI 3.72–4.57). Conclusions: Variability in each metabolic parameter was an independent predictor of the development of ESRD among the general population. There was a composite effect of the variability in additional metabolic parameters on the risk of ESRD.

Variability in Total Cholesterol Concentration Is Associated With the Risk of Dementia: A Nationwide Population-Based Cohort Study.

Introduction: Although total cholesterol (TC) variability is suggested as a risk factor for cardiovascular and cerebrovascular disease, there is no previous study to evaluate the association between TC variability and the development of dementia.Methods: Using the Korean National Health Insurance Service–Health Screening Cohort (NHIS-HEALS), the main outcomes were newly diagnosed all-cause dementia, Alzheimer's disease (AD), or vascular dementia (VaD) between January 1, 2008, and December 31, 2015. Visit-to-visit TC variability was measured as variability independent of the mean (TC-VIM), coefficient variance (TC-CV), and standard deviation (TC-SD).Results: In a total of 131,965 Koreans, there were 3,722 all-cause dementia (2.82%), 2,776 AD (2.10%), and 488 VaD (0.37%) during the median follow-up of 8.4 years. Kaplan–Meier curves showed increased cumulative incidences for all in the group of the highest quartiles of TC variability compared to the others. Regression using the Fine and Gray hazards model showed a steadily increasing risk of all-cause dementia with higher quartiles of TC variability. After adjusting for confounders including mean TC level and comparing the highest and lowest TC-VIM quartiles, the hazard ratios (HRs) for all-cause dementia and AD were 1.15 [95% confidence interval (CI) = 1.05–1.27; P = 0.003] and 1.12 (95% CI = 1.00–1.25; P = 0.040), respectively. The incidence of VaD was not significantly higher in the higher-quartile groups compared to that in the lowest-quartile group in TC-VIM variability (HR 1.22; 95% CI = 0.95–1.59; P = 0.122). These associations were consistent with TC variability defined by TC-CV or TC-SD.Conclusions: For the first time, we have demonstrated that a higher visit-to-visit variability in TC independent of mean TC is associated with an increased risk of all-cause dementia and AD in the general population.

Total cholesterol variability and risk of atrial fibrillation: A nationwide population-based cohort study.

BackgroundLong-term variability of cardiometabolic risk factors have been suggested as the risk factors for cardiovascular disease and mortality. However, the effect of long-term variability of total cholesterol (TC) on incident atrial fibrillation (AF) has not been examined.Methods and findingsWe explored whether visit-to-visit TC variability are associated with the risk of incident AF in 160,165 Korean adults, using the population-based Korean National Health Insurance Service–Health Screening Cohort (NHIS-HEALS) database, over a median duration of 8.4 years. TC variability was measured as coefficients of variance (TC-CV), standard deviation (TC-SD), and variability independent of the mean (TC-VIM). Kaplan–Meier analysis demonstrated a decreased disease-free probability in the highest quartile group of TC variability compared to that in the other groups. In the multivariate Cox proportional hazard analysis, the risk of AF increased significantly in the highest quartile group of TC variability. After multivariate adjustment for confounding variables including mean TC levels, the hazard ratio for incident AF was 1.15 (95% confidence interval 1.05–1.25; P = 0.0035) when comparing the highest with the lowest TC variability quartile (TC-CV). These relationships were consistent with TC variability defined using TC-SD or TC-VIM. Subgroup analyses, including age, sex, body mass index, and cardiometabolic disorders, showed similar results.ConclusionsThe present study is the first to demonstrate that high TC variability was associated with an increased risk of AF.

Visit-to-Visit Variability in Total Cholesterol Correlates with the Progression of Renal Function Decline in a Chinese Community-Based Hypertensive Population

Background: Studies have demonstrated that cholesterol variability is an independent predictor of cerebrovascular and cardiovascular events. Objective: This study aimed to investigate the association of visit-to-visit variability in total cholesterol (TC) with kidney decline in a Chinese community-based population. Methods: We assessed intraindividual variability in TC among 6,465 hypertensive participants and correlated the results with endpoints. TC variability was measured using standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variability independent of the mean (VIM). The endpoint of this study was progression of renal function decline defined as a decrease in estimated glomerular filtration rate (eGFR) ≥30% and to a level <60 mL/min/1.73 m² during follow-up if the baseline eGFR was ≥60 mL/min/1.73 m², or a decrease in eGFR ≥50% during follow up if the baseline eGFR was <60 mL/min/1.73 m². Results: After a median follow-up of 27 months, 13.5% (n = 877) of the participants experienced progression of renal function decline. In the multivariable-adjusted Cox model, each 1-SD increase in TC variability (by SD) increased the risk of renal function decline by 11% (HR = 1.11; 95% CI 1.034–1.197; p = 0.004); this was independent of the baseline eGFR, mean follow-up TC levels, and the lipid-lowering therapy. Similar results were found for the 3 other measures of variability, i.e., ASV, CV, and VIM. Conclusion: In subjects with hypertension, visit-to-visit variability in TC is an independent predictor of renal function decline.