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. 2024 Mar 1;31(3):232-248.
doi: 10.5551/jat.64369. Epub 2023 Aug 30.

Calculated Small Dense Low-Density Lipoprotein Cholesterol Level is A Predominant Predictor for New Onset of Ischemic Heart Disease

Masafumi Inyaku  1 , Marenao Tanaka  1   2 , Tatsuya Sato  1   3 , Keisuke Endo  1 , Kazuma Mori  4 , Itaru Hosaka  5 , Takuma Mikami  5 , Araya Umetsu  6 , Hirofumi Ohnishi  1   7 , Yukinori Akiyama  8 , Nagisa Hanawa  9 , Masato Furuhashi  1
Affiliations

Calculated Small Dense Low-Density Lipoprotein Cholesterol Level is A Predominant Predictor for New Onset of Ischemic Heart Disease

Masafumi Inyaku et al. J Atheroscler Thromb. .

Abstract

Aim: A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for ischemic heart disease (IHD). However, it remains unclear whether estimated sdLDL-C level is a predictor for IHD. We investigated the associations of new onset of IHD with levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), LDL-C and calculated sdLDL-C by Sampson's equation.

Methods: After exclusion of subjects with IHD or those with TG ≥ 800 mg/dL, a total of 18,176 subjects (men/women: 11,712/6,464, mean age: 46 years) were recruited among 28,990 Japanese individuals who received annual health checkups.

Results: During the 10-year follow-up period, 456 men (3.9%) and 121 women (1.9%) newly developed IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, obesity, smoking habit, family history of IHD, estimated glomerular filtration rate, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) (1.38 [95% confidence interval: 1.03-1.85]) for new onset of IHD in subjects with the 4th quartile (Q4) of sdLDL-C (≥ 42 mg/dL) was significantly higher than that in subjects with the 1st quartile (Q1) (≤ 24 mg/dL) as the reference, though the adjusted HRs in subjects with Q2-Q4 of TC, HDL-C, non-HDL-C, LDL-C and TG were comparable with those in subjects with Q1 of the respective lipid fractions. The adjusted HR with a restricted cubic spline increased with a higher level of calculated sdLDL-C as a continuous value at baseline.

Conclusions: sdLDL-C level calculated by Sampson's equation is a predominant predictor for the development of IHD in a general Japanese population.

Keywords: Ischemic heart disease; Small dense low-density lipoprotein cholesterol.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Supplementary Fig.1. Selection of study participants
Supplementary Fig.1. Selection of study participants
Among 28,990 individuals who received health examinations in 2006, a total of 18,176 subjects (men/women: 11,712/6,464) were finally recruited for analyses in the present study. HDL-C, high-density lipoprotein cholesterol; IHD, ischemic heart disease; TC, total cholesterol; TG, triglycerides.
Supplementary Fig.2. Correlation of levels of directly measured LDL-C and estimated LDL-C calculated by Sampson’s equation (<i>n</i>=12,960)
Supplementary Fig.2. Correlation of levels of directly measured LDL-C and estimated LDL-C calculated by Sampson’s equation (n=12,960)
LDL-C, low-density lipoprotein cholesterol
Fig.1. Prediction of new onset of IHD by levels of lipids at baseline
Fig.1. Prediction of new onset of IHD by levels of lipids at baseline
A-F. Receiver operating characteristic curves of total cholesterol (TC) (A), high-density lipoprotein cholesterol (HDL-C) (B), non-HDL-C (C), calculated low-density lipoprotein cholesterol (LDL-C) (D), triglycerides (TG) (E), and calculated small dense LDL-C (sdLDL-C) (F) at baseline to predict new onset of ischemic heart disease (IHD). AUC, area under the curve; CI, confidence interval.
Supplementary Fig.3. Hazard ratios for the development of IHD in quartiles of lipid fractions at baseline
Supplementary Fig.3. Hazard ratios for the development of IHD in quartiles of lipid fractions at baseline
Forest plots of unadjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of ischemic heart disease (IHD) in quartiles of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, calculated low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and calculated small dense low-density lipoprotein cholesterol (sdLDL-C) at baseline analyzed by Cox proportional hazard models.
Fig.2. Hazard ratios for the development of IHD in quartiles of lipid fractions at baseline
Fig.2. Hazard ratios for the development of IHD in quartiles of lipid fractions at baseline
Forest plots of adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of ischemic heart disease (IHD) in quartiles of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, calculated low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and calculated small dense low-density lipoprotein cholesterol (sdLDL-C) at baseline analyzed by Cox proportional hazard models. Confounders including age, sex, obesity, smoking habit, family history of IHD, estimated glomerular filtration rate, hypertension and diabetes mellitus at baseline were adjusted.
Fig.3. Hazard ratios for the development of IHD by lipid fractions as continuous values at baseline
Fig.3. Hazard ratios for the development of IHD by lipid fractions as continuous values at baseline
A-F. Hazard ratios (HRs) for the development of ischemic heart disease (IHD) by total cholesterol (TC) (A), high-density lipoprotein cholesterol (HDL-C) (B), non-HDL-C (C), calculated low-density lipoprotein cholesterol (LDL-C) (D), triglycerides (TG) (E), and calculated small dense LDL-C (sdLDL-C) (F) at baseline analyzed by multivariable Cox proportional hazard models with a restricted cubic spline after adjustment of age, sex, obesity, smoking habit, family history of IHD, estimated glomerular filtration rate, hypertension and diabetes mellitus at baseline. Histograms of levels of lipid fractions at baseline are also shown. Solid line: HR; dashed line: 95% confidence interval. The reference values of TC, HDL-C, non-HDL-C, LDL-C, TG and sdLDL-C were 100 mg/dL, 20 mg/dL, 50 mg/dL, 50 mg/dL, 20 mg/dL and 10 mg/dL, respectively.
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