Lipoprotein particle concentrations may explain the absence of coronary protection in the women's health initiative hormone trials.

OBJECTIVE: The Women's Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case-control substudy. METHODS AND RESULTS: We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo, and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls. Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001 versus placebo). In contrast, neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration (LDL-P). CONCLUSIONS: Postmenopausal hormone therapy-induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the randomized hormone trials.

Normal standards for QT and QT subintervals derived from a large ethnically diverse population of women aged 50 to 79 years (the Women's Health Initiative [WHI]).

Available normal standards for rate-adjusted QT intervals in women are based on samples that include only whites, and no normal standards are available for QT subintervals. This study derived normal limits from percentile distributions for QT as well as QT and T-wave subintervals in 22,311 participants in the Women's Health Initiative (WHI), including 19,059 white, 1,771 African-American, 819 Hispanic, 82 American Indian, and 580 Asian women. Excluded were women with cardiovascular disease or who were using cardioactive drugs at baseline and cardiovascular morbidity or death during the subsequent mean 6.3-year follow-up. Normal limits for QT adjusted by Bazett's formula were strongly rate dependent, invalidating their use in practical applications. QT adjusted as a linear function of RR (QTrr) or by power functions of RR with exponent 0.5 (QTsqr) or 0.42 (QT0.42) using an appropriate regression function produced rate-invariant upper and lower normal limits for rate-adjusted QT. Adjusted QT is preferable to adjusted JT because the latter requires the incorporation of QRS duration as a covariate with RR. Normal limits were also derived for T-wave subintervals. Normal limits of QTrr in Asian women were 10 ms longer than in other ethnic groups. In conclusion, QT adjusted for rate as a linear function of RR is preferable to JT and other QT subintervals in the evaluation of QT prolongation. The adaptation of considerable revisions of the currently used limits for prolonged QT in women is suggested, with an additional race-specific adjustment in Asian women. Bazett's formula is inappropriate for testing new drugs or other applications.