Elevated level of estimated small dense LDL cholesterol is independently associated with the development of hypertension, regardless of LDL cholesterol level.

An elevated level of small dense low-density lipoprotein cholesterol (sdLDL-C) is a risk factor for cardiovascular diseases, including hypertension. However, it remains unclear whether the sdLDL-C level is a predictor for the development of hypertension independent of LDL-C level. We investigated the associations of new onset of hypertension with four categorized groups of high (H-) and low (L-) levels of sdLDL-C calculated by the Sampson equation and LDL-C using cut-off values of sdLDL-C/LDL-C (29.6/114 mg/dL) by receiver operating characteristic curves in 15,204 Japanese participants (men/women: 9230/5794, mean age: 46 years) who received annual health checkups. During a 10-year follow-up period (median duration: 6.0 years), 3,054 subjects (men/women: 2332 [25.3%]/722 [12.5%]) newly developed hypertension. Kaplan-Meier survival curves showed a distinct difference in the cumulative incidence of hypertension between high (H-sdLDL-C/H-LDL-C and H-sdLDL-C/L-LDL-C) and low (L-sdLDL-C/H-LDL-C and L-sdLDL-C/L-LDL-C) sdLDL-C groups. Multivariable Cox proportional hazard model analysis adjusting for age, sex, family history of hypertension, systolic blood pressure, obesity, habits of current smoking and alcohol drinking, and diagnosis of diabetes mellitus and chronic kidney disease showed that hazard ratios [95% confidence intervals] were significantly higher in participants with H-sdLDL-C/H-LDL-C (1.21 [1.09-1.34]) and participants with H-sdLDL-C/L-LDL-C (1.25 [1.10-1.41]) than in participants with L-sdLDL-C/L-LDL-C as the reference. Linear mixed effects model analysis showed that there was a significant interaction of sdLDL-C, but not LDL-C, with systolic blood pressure for the follow-up period. In conclusion, a high level of estimated sdLDL-C can predict the development of hypertension regardless of LDL-C level in a general Japanese population.