Dr Fergus McCarthy takes a monthly look at articles just published in the area of hypertension & pre-eclampsia…

 

Chronic Hypertension

The lifelong impact of adverse pregnancy outcomes, in particular pre-eclampsia continues to generate interesting research. Timpka and colleagues explore the topic of lifestyle and the role of modifiable risk factors in the subsequent development of chronic hypertension following pregnancy complicated by hypertensive disorders of pregnancy (HDP).1 In this study HDP referred to gestational hypertension and pre-eclampsia. The Nurses Health study II was a prospective cohort study that recruited 116,429 female US registered nurses and was conducted between 1991 and 2013, This study included data from 54,588 eligible women between the ages of 32 to 59 years with data on reproductive history and without previous chronic hypertension, stroke, or myocardial infarction were recruited. The main outcome measure was chronic hypertension diagnosed by a physician.

The association between the development of chronic hypertension, history of hypertensive disorders of pregnancy and four lifestyle risk factors were examined. The four lifestyle risk factors were post-pregnancy body mass index, physical activity, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, and dietary sodium/potassium intake.

10% (n=5520) of women had a history of HDP at baseline. 13,971 cases of chronic hypertension occurred during 689,988 person years of follow-up. Being overweight or obese was the only lifestyle factor consistently associated with a higher risk of chronic hypertension. Higher body mass index, in particular, also increased the risk of chronic hypertension associated with history of HDP (relative excess risk due to interaction P<0.01 for all age strata). For example, in women aged 40-49 years with previous HDP and obesity class I (body mass index 30.0-34.9), 25% (95% confidence interval 12% to 37%) of the risk of chronic hypertension was attributable to a potential effect of obesity that was specific to women with previous HDP.

Lifestyle and Risk Reduction

This study provides an interesting next step into how we may advocate for change and promote the prevention of adverse cardiovascular outcomes in women with a history of hypertensive disorders of pregnancy. The risk of chronic hypertension after HDP might be markedly reduced by adherence to a beneficial lifestyle. Compared with women without a history of HDP, keeping a healthy weight seems to be especially important for women with a history of HDP. Interestingly, both gestational hypertension and pre-eclampsia had similar results when examined separately.

Further epidemiological studies were published in the past month adding to the growing body of evidence supporting adverse cardiovascular outcomes following hypertensive disorders of pregnancy. In their study McDonald et al examined data from the GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-PRemature Acute Coronary SYdrome) study, a prospective multicenter study, with recruitment between January 2009 and April 2013, including 242 parous women with premature acute coronary syndrome.2 Of women included in the study, 43 (17.8%) women had prior gestational hypertension, 33 (13.6%) pre-eclampsia and 166 (68.6%) a prior normotensive pregnancy. Women with a history of HDP commonly had chronic hypertension and diabetes and those presenting with ST-elevation myocardial infarction were more likely to have a history of pre-eclampsia (aOR 3.12, 95% CI 1.22-8.01) than were women with prior normotensive pregnancies. Neither gestational hypertension (aOR 1.40, 95% CI 0.60-3.26) nor pre-eclampsia (aOR 0.63, 95% CI 0.23-1.74) was associated with a higher composite risk of three-vessel, left main or proximal left anterior descending coronary disease.

Bokslag et al examined the effect of early onset (<34 weeks’ gestation) pre-eclampsia on cardiovascular disease in the 5th decade of life.3 This prospective observational study of 131 women with early onset pre-eclampsia and 56 normotensive controls had a cardiovascular risk assessment performed 9-16 years after their index pregnancy. Women with a history of early-onset pre-eclampsia had significantly greater systolic and diastolic blood pressure, greater body mass index, more often had an abnormal lipid profile (lower high-density lipoprotein levels, higher triglycerides), greater glycated hemoglobin, and greater levels of albuminuria compared to controls.

Preventative Measures

None of the women with a history of early-onset pre-eclampsia was diagnosed with cardiovascular disease; 38.2% were diagnosed with hypertension; and 18.2% were diagnosed with metabolic syndrome. A total of 42% met the criteria for the window of opportunity for preventive measures. In women with a history of an uncomplicated pregnancy, no women were diagnosed with cardiovascular disease; 14.3% were diagnosed with hypertension; 1.8% with metabolic syndrome. In this cohort, 14.3% met the criteria for the window of opportunity for preventive measures. These women are currently outside the scope of most preventive programs due to their relatively young age, but have important modifiable risk factors for cardiovascular diseases.

Finally, the role of inflammation in the underlying pathogenesis of pre-eclampsia was revisited by Ferguson et al.3 The authors rightly argued that many of the studies to date are limited by size or study design and conducted a robust examination of inflammatory markers during pregnancy. The authors used samples from 441 women in the LIFECODES prospective birth cohort, which included 50 mothers who experienced pre-eclampsia and 391 mothers with normotensive pregnancies. Participants provided urine and plasma samples at 4 time points during gestation (median, 10, 18, 26, and 35 weeks) that were analysed for a panel of oxidative stress and inflammation markers.

The authors demonstrated using adjusted models, that hazard ratios of pre-eclampsia were significantly (P<.01) elevated in association with all inflammation biomarkers that were measured at visit 2 (median, 18 weeks; hazard ratios, 1.31-1.83, in association with an interquartile range increase in biomarker).

Hazard ratios at 18 weeks gestation were the most elevated for C-reactive protein, for interleukin-1β, -6, and -10, and for the oxidative stress biomarker 8-isoprostane (hazard ratio, 1.68; 95% confidence interval, 1.14-2.48) compared to other time points. Hazard ratios for tumor necrosis factor-α were consistently elevated at all 4 of the study visits (hazard ratios, 1.49-1.63; P<.01). These associations were attenuated within groups typically at higher risk of experiencing pre-eclampsia, including African American mothers, mothers with higher body mass index at the beginning of gestation, and pregnancies that ended preterm.

While perhaps not useful from a prediction or diagnostic point of view, this inflammatory state may be a significant contributing factor to the long term risks increasingly associated with HDP.

References

  1. Timpka S, Stuart JJ, Tanz LJ, Rimm EB, Franks PW, Rich-Edwards JW. Lifestyle in progression from hypertensive disorders of pregnancy to chronic hypertension in Nurses’ Health Study II: observational cohort study. BMJ. 2017;358:j3024.
  2. McDonald EG, Dayan N, Pelletier R, Eisenberg MJ, Pilote L. Premature cardiovascular disease following a history of hypertensive disorder of pregnancy. Int J Cardiol. 2016;219:9-13.
  3. Bokslag A, Teunissen PW, Franssen C, et al. Effect of early-onset preeclampsia on cardiovascular risk in the fifth decade of life. Am J Obstet Gynecol. 2017;216(5):523 e521-523 e527.