Lipoprotein Subclass Abnormalities and Incident Hypertension in Initially Healthy Women

Study Questions:

What is the role of traditional lipids, particularly decreased high-density lipoprotein (HDL) cholesterol and increased triglycerides, as well as lipoprotein particle size and subclass concentrations, in the development of hypertension?


Lipoprotein abnormalities, particularly smaller low-density lipoprotein (LDL) size and increased concentrations of triglyceride-rich particles, may contribute to hypertension by impairing endothelial function and promoting insulin resistance and vascular inflammation. A total of 17,527 initially healthy women without baseline hypertension enrolled in the Women’s Health Study were prospectively followed for 8 years. At baseline, information regarding traditional lipids and hypertension risk factors was obtained, and lipoprotein size and subclass concentrations were measured by nuclear magnetic resonance spectroscopy. Patients were excluded if they had hypertension (blood pressure and hypertensive status were self-classified by the patients).


Baseline lipoprotein size and subclass concentrations were significantly associated with incident hypertension. Although LDL cholesterol was not associated with hypertension (odds ratio [OR] for quintile 5 vs. 1, 1.1; 95% confidence interval [CI], 0.96-1.2), increased concentrations of LDL particles were associated with greater risk (OR, 1.7; 95% CI, 1.5-2.0), especially small LDL particles (OR, 1.6; 95% CI, 1.5-1.8). Increased HDL cholesterol was associated with lower risk of hypertension (OR for quintile 5 vs. 1, 0.8; 95% CI, 0.7-0.9). By contrast, increased concentrations of HDL particles had greater risk (OR, 1.5; 95% CI, 1.3-1.7), especially small HDL particles (OR, 1.4; 95% CI, 1.2-1.5), whereas large HDL particles had lower risk (OR, 0.8; 0.7-0.9). Triglycerides and triglyceride-rich very LDL (VLDL) particles were positively associated with hypertension, with large VLDL particles associated with greater risk (OR, 1.7; 95% CI, 1.5-1.9). Adding particle subclasses improved discrimination over a model with traditional lipids and risk factors (c-statistic, 0.671-0.676; p < 0.001).


In this study of initially healthy women, lipoprotein particle size and subclass concentrations were associated with incident hypertension, and provided additive information to traditional lipids and risk factors.


This is a fascinating and potentially important description from the Women’s Health Study of the association of both small LDL and HDL particles, and large VLDL particles and hypertension. This association was not observed with the simple measurement of LDL cholesterol. These data and others provide an increasing rich substrate for the idea that particle number or apolipoprotein measurements may provide additional help in the evaluation of cardiovascular risk.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Hypertension

Keywords: Biological Markers, Hypertriglyceridemia, Cardiovascular Diseases, Lipoproteins, Women's Health, Risk Factors, Insulin Resistance, Triglycerides, Magnetic Resonance Spectroscopy, Hypertension

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