Association of cumulative low-density lipoprotein cholesterol exposure with vascular function

•Cumulative LDL-C exposure, calculated by age × LDL-C, had significant negative correlations with FMD value and NID value and significant positive correlations with mean CCA-IMT and maximum CCA-IMT in subjects not being treated with lipid-lowering drugs. •Endothelial dysfunction was found to be induced by cumulative LDL-C exposure of >4000 mg·year/dL, vascular smooth muscle damage >5000 mg·year/dL, and increase in IMT and plaque formation ≥6000 mg·year/dL. •Cumulative LDL-C calculated by age × LDL-C is useful for assessing the progression of atherosclerosis. Background The relationship between cumulative low-density lipoprotein cholesterol (LDL-C) exposure and progression of atherosclerosis remains uncertain. Objective The aim of this study was to determine the relationship between cumulative LDL-C level and flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID) and the presence of plaque in the common carotid artery (CCA). Methods This was a cross-sectional study. We measured FMD in 8208 subjects, NID in 1822 subjects, and CCA plaque in 591 subjects who were not taking lipid-lowering drugs. The subjects were divided into four groups based on cumulative LDL-C exposure: <4000 mg·year/dL, 4000–4999 mg·year/dL, 5000–5999 mg·year/dL, and ≥6000 mg·year/dL. Results The odds ratio of the lower quartile of FMD in the cholesterol-year-score <4000 mg·year/dL group was significantly higher than the odds ratios in the other groups. The odds ratio of the lower quartile of NID in the <4000 mg·year/dL group was significantly higher than the odds ratios in the 5000–5999 mg·year/dL and ≥6000 mg·year/dL groups. The odds ratio of the prevalence of CCA plaque in the <4000 mg·year/dL group was significantly higher than that in the ≥6000 mg·year/dL group. Conclusions Endothelial dysfunction occurred from cumulative LDL-C exposure of 4000 mg·year/dL, vascular smooth muscle dysfunction occurred from cumulative LDL-C exposure of 5000 mg·year/dL, and prevalence of CCA plaque occurred from cumulative LDL-C exposure of 6000 mg·year/dL. Clinical Trial Registry Information http://www.umin.ac.jp (UMIN000012950, UMIN000012951, and UMIN000012952, UMIN000003409) The relationship between cumulative low-density lipoprotein cholesterol (LDL-C) exposure and progression of atherosclerosis remains uncertain. The aim of this study was to determine the relationship between cumulative LDL-C level and flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID) and the presence of plaque in the common carotid artery (CCA). This was a cross-sectional study. We measured FMD in 8208 subjects, NID in 1822 subjects, and CCA plaque in 591 subjects who were not taking lipid-lowering drugs. The subjects were divided into four groups based on cumulative LDL-C exposure: <4000 mg·year/dL, 4000–4999 mg·year/dL, 5000–5999 mg·year/dL, and ≥6000 mg·year/dL. The odds ratio of the lower quartile of FMD in the cholesterol-year-score <4000 mg·year/dL group was significantly higher than the odds ratios in the other groups. The odds ratio of the lower quartile of NID in the <4000 mg·year/dL group was significantly higher than the odds ratios in the 5000–5999 mg·year/dL and ≥6000 mg·year/dL groups. The odds ratio of the prevalence of CCA plaque in the <4000 mg·year/dL group was significantly higher than that in the ≥6000 mg·year/dL group. Endothelial dysfunction occurred from cumulative LDL-C exposure of 4000 mg·year/dL, vascular smooth muscle dysfunction occurred from cumulative LDL-C exposure of 5000 mg·year/dL, and prevalence of CCA plaque occurred from cumulative LDL-C exposure of 6000 mg·year/dL.