Lipoprotein(a) Prognostic of CHD in Contemporary Cohort Receiving Menopausal Hormone Therapy
Key findings
- In a previous large epidemiologic study that enrolled women nearly 30 years ago, the use of menopausal hormone therapy (HT) was tied to a modest reduction in lipoprotein(a) (Lp[a]) and less risk of Lp(a)-associated atherosclerotic cardiovascular disease
- Because patterns of HT use have changed considerably in more recent years, Massachusetts General Hospital researchers re-studied those relationships in 88,266 postmenopausal participants in the UK Biobank
- Current HT use was associated with modest Lp(a) reduction, by 7.5 nmol/L compared with previous HT use, and by 7.9 nmol/L compared with never use (P<0.001 for both comparisons)
- In contrast to the previous large study, the risk of Lp(a)-associated coronary heart disease was significantly greater in women who previously used HT and those currently using HT than in those who never used HT
- Regardless of HT use, clinicians should measure Lp(a) in postmenopausal individuals if clinically indicated
In 2008, a study of 27,736 women published in the Journal of the American College of Cardiology concluded that the use of menopausal hormone therapy (HT) is associated with a modest reduction in lipoprotein(a) (Lp[a]) and less risk of Lp(a)-associated atherosclerotic cardiovascular disease (CVD). The study participants were enrolled nearly 30 years ago.
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Since then, indications and patterns of HT use have changed considerably. In a larger, more contemporary cohort, Massachusetts General Hospital researchers have again linked HT use to a reduction in Lp(a) but found no evidence that HT use reduces the risk of Lp(a)-associated coronary heart disease.
Michael C. Honigberg, MD, MPP, cardiologist at the Corrigan Minehan Heart Center at Mass General, Pradeep Natarajan, MD, MMSc, director of the Cardiovascular Disease Prevention Center and investigator in the Cardiovascular Research Center, and Mark Trinder, MSc, a medical student in Dr. Natarajan's lab, report the results in a research letter published in JAMA Cardiology.
Methods
The team studied 88,266 participants in the UK Biobank (average age 60) who were postmenopausal at enrollment from 2006 to 2010 and had no history of atherosclerotic CVD, heart failure, aortic stenosis, or venous thromboembolism. At enrollment, 5% were using HT, and 39% reported previous HT use. The median follow-up was 11 years.
HT Use and Lp(a)
Consistent with the previous large epidemiologic study, HT use was associated with Lp(a) reduction after adjustment for age, use of cholesterol-lowering medication, and LPA genetic risk score. Compared with current HT users:
- Previous HT users had higher Lp(a) by 7.5 nmol/L (P<0.001)
- Never HT users had higher Lp(a) by 7.9 nmol/L (P<0.001)
Lp(a) and Coronary Heart Disease (CHD)
In contrast to the previous study, higher Lp(a) values were associated with an increased risk of newly diagnosed CHD:
- Women in the highest Lp(a) quartile had the highest risk of CHD (adjusted HR, 1.15 compared with the lowest quartile; P=0.003)
- The risk of Lp(a)-associated CHD was greater in women who previously used HT (P for interaction = 0.046) and those currently using HT (P for interaction = 0.04) than in those who never used HT
Applying the Findings to the Clinic
These data affirm that Lp(a) levels are prognostic of CHD in women receiving HT. Regardless of HT use, clinicians should not be dissuaded from measuring Lp(a) in postmenopausal women if clinically indicated.
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