Lipoprotein Subclass Abnormalities and Incident Hypertension in Initially Healthy Women

BACKGROUND: Abnormalities in traditional lipids, particularly decreased HDL cholesterol and increased triglycerides, can precede the onset of hypertension. Whether lipoprotein particle size or subclass concentrations play a role in the development of hypertension is unknown. METHODS: We followed 17 527 initially healthy women without baseline hypertension prospectively 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. RESULTS: 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: 1.08 (95% CI 0.96-1.20)], increased concentrations of LDL particles were associated with greater risk [OR 1.73 (1.54-1.95)], especially small LDL particles [OR 1.62 (1.45-1.83)]. Increased HDL cholesterol was associated with lower risk of hypertension [OR for quintile 5 vs 1: 0.79 (0.70-0.89)]. By contrast, increased concentrations of HDL particles had greater risk [OR 1.48 (1.32-1.67)], especially small HDL particles [OR 1.36 (1.22-1.53)], whereas large HDL particles had lower risk [OR 0.80 (0.71-0.90)]. Triglycerides and triglyceride-rich VLDL particles were positively associated with hypertension, with large VLDL particles associated with greater risk [OR 1.68 (1.50-1.89)]. Adding particle subclasses improved discrimination over a model with traditional lipids and risk factors (c-statistic 0.671 compared to 0.676; P < 0.001). CONCLUSIONS: 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.