- This study examined whether genetic predisposition to cardiometabolic traits and genetic variants related to antihypertensive medication targets are associated with hypertensive disorders of pregnancy (HDP)
- The researchers constructed genetic instruments for each trait and medication target and calculated polygenic risk scores for each of 214,365 women in the UK Biobank who had reported one or more live births
- For both systolic and diastolic blood pressure, the OR for hypertensive disorders of pregnancy per standard deviation of polygenic risk score was 1.22; for body mass index, the OR was 1.06
- Genetic variants mimicking the effects of beta-blockers, calcium channel blockers and nitrates all demonstrated reduction in HDP risk proportional to effects on systolic blood pressure
- Blood pressure and BMI may be viable targets for reducing the risk of HDP
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Hypertensive disorders of pregnancy (HDP) increase the risk of maternal and fetal morbidity and mortality, as well as cardiovascular disease later in life. Certain preventive measures taken before or during pregnancy could reduce the incidence of HDP, researchers at Massachusetts General Hospital have found.
Specifically, Michael C. Honigberg, MD, MPP, cardiologist, and Pradeep Natarajan, MD, MMSc, director of the Cardiovascular Disease Prevention Center at Mass General, and colleagues determined that genetic predisposition to elevated blood pressure and higher body mass index (BMI) are significantly associated with HDP. They report their findings in a research letter in Circulation.
To distinguish between correlation and causation, the researchers made use of Mendelian randomization, an epidemiological approach to assessing whether a modifiable risk factor has a causal effect on an outcome based on observational data. It relies on the use of genetic variants that are strongly associated with the risk factor.
Using genome-wide association data from previous studies, the team constructed genetic instruments for cardiometabolic risk factors using single-nucleotide polymorphisms (SNPs):
- Systolic blood pressure (SBP)—75 SNPs
- Diastolic blood pressure (DBP)—75 SNPs
- BMI—141 SNPs
- Resting heart rate—28 SNPs
- Low-density lipoprotein cholesterol—277 SNPs
- Type 2 diabetes—64 SNPs
- Ever-smoking—10 SNPs
They also constructed genetic variants that mimicked the targets of antihypertensive medications:
- Beta-blockers—3 SNPs
- Calcium channel blockers—13 SNPs
- Nitrates—3 SNPs
The researchers calculated a polygenic risk score (PRS) for each of 214,365 women in the UK Biobank, average age of 57, who had reported ≥1 live birth. 2,772 of them (1.3%) had experienced an HDP.
The researchers found the following:
- SBP—The OR for HDP per standard deviation of PRS was 1.22 (P < .001)
- DBP—Same result as for SBP
- BMI—OR, 1.06 per standard deviation of PRS (P = .004)
- Beta-blockers—OR, 0.55 per 5-mmHg reduction in SBP (P = .02)
- Calcium channel blockers—OR, 0.68 per 5-mmHg reduction in SBP (P = .004)
- Nitrates—OR, 0.56 per 5-mmHg reduction in SBP (P = .02)
The PRSs for blood pressure and BMI were independent and additive. The genetic predisposition for increased heart rate, diabetes, smoking, and higher low-density lipoprotein cholesterol were not significantly associated with HDP.
The results imply that elevated SBP, DBP and BMI are causal factors in the development of HDP. Blood pressure and BMI may therefore be viable targets for reducing HDP risk. They also help explain previously described epidemiologic associations of HDP with chronic hypertension and obesity.
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