Cardio-vascular (heart) disease is the leading cause of mortality in developed countries. Among the cardio-vascular risk factors appearing early in life are hypertensive disorders of pregnancy-included high blood pressure, possibly associated with protein in the urine after 20 weeks of pregnancy (preeclampsia). They affect 10% of pregnant women and some of them have persistent high blood pressure after delivery, which damage the cardio-vascular system with long-term complications. Post-partum management, during the 6 weeks following delivery, of hypertensive disorders of pregnancy to achieve normal blood pressure could prevent long-term cardio-vascular diseases, and preliminary evidence suggests that intervening earlier may have a long-term impact. The potential impact of immediate post-partum management on long-term cardio-vascular diseases has not yet been investigated.
The aim of this study is to assess the association between the effective post-partum management of hypertensive disorders of pregnancy at 3 time points in the post-partum period (6 weeks, 6 and 12 months) and long-term cardio-vascular diseases.
We will include all pregnant women in the UK with hypertensive disorders of pregnancy between 2000 and 2020 and compare women with effective post-partum management, defined as normalisation of blood pressure, to women with ineffective management.
If a positive impact is observed, the expected public health benefit is via informing guideline development for optimising post-partum management of blood pressure after hypertensive diseases of pregnancy. The implication for the care system and clinical practice would be the implementation of multidisciplinary management to ensure close follow-up for women at high-risk with appropriate information and early prevention.
Hypertensive disorders of pregnancy increase risk of long-term cardiovascular diseases. Early prevention by post-partum blood pressure control has an impact on short-term blood pressures values and preliminary evidence suggests that intervening at this stage may have an important long-term impact. But to our knowledge, the potential impact of post-partum management on long-term cardio-vascular diseases has not yet been investigated.
The aim is to assess the association between effective post-partum management of hypertensive disorders of pregnancy and long-term cardio-vascular diseases.
The study population of this retrospective population-based cohort study, will be pregnant women with hypertensive disorders of pregnancy between 2000-2020 in the UK and included in the CPRD.
Exposure will be the effective post-partum management of hypertensive disorders of pregnancy defined by the normalisation of blood pressure (<140/90 mmHg) at three time points: 6 weeks, 6 and 12 months post-partum.
Outcomes will be a composite of cardio-vascular mortality and 12 cardio-vascular diseases conditions selected by CALIBER EHR-algorithms.
The CPRD pregnancy register will be used and additional information will be obtained through linkage to HES and ONS death registration data.
The association between blood pressure management and cardio-vascular diseases occurrence can be influenced by the severity of hypertensive disorder of pregnancy. To address this bias, we will use the inverse of the probability of having severe hypertensive disorder of pregnancy conditional on maternal and pregnancy characteristics, in multivariable weighted for each woman. Then we will use a Cox model regression to study the association between exposed and non-exposed women.
A better understanding of the impact of post-partum management of hypertensive disorders of pregnancy on maternal long-term cardio-vascular diseases would improve the quality of information, early prevention and follow-up for women at risk. It would inform guideline development and potentially the implementation of multidisciplinary management to ensure close follow-up in the post-partum period.
The primary outcome is a composite of cardio-vascular morbidity and mortality very similar to the primary outcome of the Leon et al study conducted within the CPRD database to investigate the association between preeclampsia, hypertensive disorders of pregnancy, and subsequent diagnosis of 12 different cardiovascular disorders (1). The phenotypes of the cardio-vascular diseases will be defined using all inferred or diagnosed cases of previously validated and replicable CALIBER EHR-algorithms (https://www.caliberresearch.org/portal/) (2–6). They describe a wide range of acute and chronic cardio-vascular diseases including both fatal and nonfatal presentations that are relevant to inform the success of primary prevention. They include the 12 most common symptomatic manifestations of cardio-vascular diseases, irrespective of underlying disease mechanism, arising from pathology in the head, heart, abdomen, or legs.
The 12 cardio-vascular disorders selected as outcomes are as follows: ischemic stroke; intracerebral haemorrhage; subarachnoid haemorrhage; stroke not otherwise specified; myocardial infarction; stable angina; unstable angina; coronary heart disease not otherwise specified; peripheral arterial disease; abdominal aortic aneurysm; atrial fibrillation; and heart failure.
In addition, we will use the end point of cardio-vascular death using Office for National Statistics underlying cause of death data as recorded on death certificates. Any record of cause coded within the ICD10 ‘I’ branch or the ICD9 39 to 45 branches will be considered a cardio-vascular death.
Then, for secondary analyses, composite outcomes will be created according to the following groupings, similar to Leon et al study: all stroke (ischemic stroke; intracerebral haemorrhage; subarachnoid haemorrhage; stroke not otherwise specified); all peripheral disease (peripheral arterial disease; abdominal aortic aneurysm); cardiac atherosclerotic (myocardial infarction; stable angina; coronary heart disease not otherwise specified); other cardio-vascular (heart failure; atrial fibrillation).
Secondary outcomes include postpartum care (blood pressure measurement, medication use), physical and mental health (including postpartum depression, pelvic/perineal pain, incontinence). Where possible, we will use existing published code lists (such as the code list for depression from Tianyi et al (2022) (53)), or new lists will be developed with clinical input as needed.
Claire Carson - Chief Investigator - University of Oxford
Claire Carson - Corresponding Applicant - University of Oxford
Aden Kwok - Collaborator - University of Oxford
Claire Carson - Collaborator - University of Oxford
Marian Knight - Collaborator - University of Oxford
Rema Ramakrishnan - Collaborator - University of Oxford
Yangmei Li - Collaborator - University of Oxford
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Pregnancy Register