Greater Low-Density Lipoprotein Cholesterol Variability Increases the Risk of Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

Hsu, Wei-Hao; Lai, Chia-Wei; Chen, Szu-Chia; Chiou, Hsin-Ying Clair; Hsiao, Pi‐Jung; Shin, Shyi–Jang; Lee, Mei‐Yueh

doi:10.4158/ep-2019-0002

Cited by 13 publications

(13 citation statements)

References 22 publications

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“…Additionally, this study also revealed a possible gender effect on the relationship between LDL-C variability and CVD risk and mortality, with a stronger association in males than in females. Although the exact mechanism requires further elucidation, it has been suggested that LDL-C tends to be more variable in females than in males, 5,8,11 predominantly as a result of hormonal fluctuations in female menstrual cycles. 28 Consequently, females may be more adaptable to cholesterol variability, hence exhibiting a smaller effect in CVD risk regardless of the greater LDL-C variability.…”

Section: Discussionmentioning

confidence: 99%

“…showed an association between CVD risk and LDL-C variability, but not for triglycerides variability. 11 This could be explained by an illdefined cohort, with 10% of recruited patients having a diagnostic history of CVD. Furthermore, the effect of triglycerides variability could also be overshadowed in patients with severe health conditions.…”

Section: Discussionmentioning

confidence: 99%

“…There have been eight studies evaluating the associations between cholesterol variability and the risk of CVD and mortality. [4][5][6][7][8][9][10][11] Of these, seven focused on either general 4 or CVD populations, [5][6][7][8][9][10] and thus may appear inapplicable to diabetes populations without CVD. Only one study focused on a diabetes population, thereby indicating the detrimental effects of low-density lipoprotein-cholesterol (LDL-C) variability, although such impacts were not exhibited in triglycerides and high-density lipoprotein-cholesterol (HDL-C).…”

Section: Introductionmentioning

confidence: 99%

“…Only one study focused on a diabetes population, thereby indicating the detrimental effects of low-density lipoprotein-cholesterol (LDL-C) variability, although such impacts were not exhibited in triglycerides and high-density lipoprotein-cholesterol (HDL-C). 11 This study also included a group of patients with CVD, therefore it was potentially susceptible to reverse causality. Furthermore, nearly all current studies have included a comparatively small number of patients and outcome events [7][8][9][10][11] or have introduced informative censoring and immortal time bias through the inclusion of postbaseline measurements when determining cholesterol variability.…”

Section: Introductionmentioning

confidence: 99%

“…11 This study also included a group of patients with CVD, therefore it was potentially susceptible to reverse causality. Furthermore, nearly all current studies have included a comparatively small number of patients and outcome events [7][8][9][10][11] or have introduced informative censoring and immortal time bias through the inclusion of postbaseline measurements when determining cholesterol variability. [5][6][7][8] Moreover, none of these studies accounted for measurement error in their measures of cholesterol variability, so the association between cholesterol variability between event outcomes may be biased because of regression dilution bias.…”

Section: Introductionmentioning

confidence: 99%

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Greater variability in lipid measurements associated with cardiovascular disease and mortality: A 10‐year diabetes cohort study

Wan

Chin

et al. 2020

Diabetes Obesity Metabolism

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Aim To examine the associations between variability in lipids and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes based on low‐density lipoprotein‐cholesterol (LDL‐C), the total cholesterol (TC) to high‐density lipoprotein‐cholesterol (HDL‐C) ratio and triglycerides (TG). Materials and methods A retrospective cohort study included 125 047 primary care patients with type 2 diabetes aged 45‐84 years without CVD during 2008‐2012. The variability of LDL‐C, TC to HDL‐C and TG was determined using the standard deviation of variables in a mixed effects model to minimize regression dilution bias. The associations between variability in lipids and CVD and mortality risk were assessed by Cox regression. Subgroup analyses based on patients’ baseline characteristics were also conducted. Results A total of 19 913 CVD events and 15 329 mortalities were recorded after a median follow‐up period of 77.5 months (0.8 million person‐years), suggesting a positive linear relationship between variability in lipids and the risk of CVD and mortality. Each unit increase in the variability of LDL‐C (mmol/L), the TC to HDL‐C ratio and TG (mmol/L) was associated with a 27% (HR: 1.27 [95% CI: 1.20‐1.34]), 31% (HR:1.31 [95% CI: 1.25‐1.38]) and 9% (HR: 1.09 [95% CI: 1.04‐1.15]) increase in the risk of composite endpoint of CVD and mortality, respectively. Age‐specific effects were also found when comparing LDL‐C variability, with patients aged 45‐54 years (HR: 1.70 [95% CI: 1.42‐2.02]) exhibiting a 53% increased risk for the composite endpoints than those aged 75‐84 years (HR: 1.11 [95% CI: 1.01‐1.23]). Similar age effects were observed for both the TC to HDL‐C ratio and TG variability. Significant associations remained consistent among most of the subgroups. Conclusions Variability in respective lipids are significant factors in predicting CVD and mortality in primary care patients with type 2 diabetes, with the strongest effects related to LDL‐C and the TC to HDL‐C ratio and most significant in the younger age group of patients aged 45‐54 years. Further study is warranted to confirm these findings.

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