Pregnancy-induced hypertension (PIH) affects up to 10% of pregnancies and is characterized by systolic blood pressure (SBP) exceeding 140 mmHg and diastolic blood pressure (DBP) exceeding 90 mmHg¹. PIH includes four conditions: gestational hypertension, preeclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia. PIH is not only the second leading cause of maternal morbidity and mortality² but also a leading cause of neonatal morbidity and mortality due to perinatal asphyxia. Though these are the well-known complications, PIH has also proven to produce remote complications like cardiovascular diseases.³ Studies have also predicted that it is an independent predictor of peripheral arterial disease (PAD).⁴ The correlation between PIH and PAD is still being researched, but studies suggest that women with a history of PIH should be monitored for PAD risk factors and symptoms, especially if they have other cardiovascular risk factors also. Ankle-brachial index (ABI) is highly effective in diagnosing 50% stenosis in lower extremity arteries, with a sensitivity exceeding 90% and specificity over 95%.^5,6  With this background our study was planned to study the risk for PAD by estimating ABI in women with history of PIH after a period of 5 years following childbirth.

Aims and Objectives:

1. To estimate the risk of PAD among normal pregnant women and pregnant women with Hypertension in Pregnancy
2. To determine the risk factors for development of PAD in these mothers

    
Methodology:

The study was a prospective cohort study conducted among antenatal women attending the Obstetrics and Gynecology OPD in Indira Gandhi Medical College and Research Institute. The study included 2 groups as follows, Group 1: normal pregnant mothers with no added co-morbid risk and Group 2: primigravidae with pregnancy induced hypertension: two recordings of BP more than 140/90 mm hg taken six hours apart after 20 weeks of gestation. All consecutive pregnant women fulfilling the inclusion criteria were included in the study after an informed consent. Personal data regarding, age, education, occupation, place of residence was collected. All participants were subjected to a questionnaire (Southern California Heart Specialist’s Patient Questionnaire on “Are you at risk for PAD”) regarding symptoms of PAD and presence of other risk factors for PAD. Following this Ankle Brachial Index (ABI) was calculated at 34 weeks of gestation to identify present risk for PAD. Detailed information for communication and follow up was collected from all participants. Both the groupd were followed up after 5 years to identify long term risk for PAD.  Qualitative data will be was analyzed using Microsoft excel and epi-info computer software. Suitable statistical tests (chi-square test, independent t-test) was be used to assess significance of study findings. Sample size was calculated assuming a difference of 30% between 2 groups, α - 0.05, power – 80%. The total sample size for 2 groups was 60, i.e 30 in each group. Accounting for the attrition (20% over 5 years), the corrected sample size was 36 patients in each group. Multigravida and primigravida with co-exsisting other co-morbid conditions were excluded from the study.

Results:

Table 1: Assessment of symptoms and risk factors for PAD based on Southern California Heart Specialist’s Patient Questionnaire

From the results of the study, it was observed that there was no statistically significant difference in presentation between the two groups, both at the time of enrolment into the study and at five years’ follow-up. Four patients among normotensive patients and 11 patients among PIH patients presented with cramp in legs during exercise. But except for one patient in each group, all their symptoms were relieved with rest. At five years, follow-up, only one patient in normotensive group had symptoms of leg cramps, but was relieved on rest. Where is among PIH patients 8 patients (32%) of the total 25 patients who were followed up at five years following delivery had cramps in legs following exercise. in these eight patients, four of them had relief of pain with rest. Risk factors like 2 patients with coronary heart disease, 3patients with diabetes and 2 patients with hyperlipidemia were identified in the PIH group at five years’ follow-up.

Table 2: ABI in PIH and Normotensive patients and odds ratio at five years

Ankle Brachial Index (ABI) was calculated at five years, follow-up in both the exposed and non-exposed group. ABI <0.09 was considered as indicator of PAD. Four patients in exposed group and two patients in non-exposed group had ABI <0.09, with an odds ratio of 3.12.

Discussion:

This study was planned to study the risk for PAD after a period of 5 years following childbirth by estimating ABI in women with history of PIH. Not many studies are available describing the risk of PAD in patients with PIH. One major study one almost 1 million Canadian women reported a fourfold increase in PAD risk three decades after a pregnancy that was complicated by maternal placental syndrome (PIH, placental abruption or placental infarction).⁷ Other studies had conflicting results on association of PIH and PAD as they were based on whether patients had intermittent claudication.

Peripheral arterial disease (PAD) is characterized by the narrowing of peripheral arteries, typically due to atherosclerosis, smoking, diabetes, hypertension, obesity, and hypercholesterolemia. The hallmark symptom of PAD is intermittent claudication (IC), which involves cramping, pain, or fatigue in the lower extremities triggered by exertion and relieved by rest within approximately 10 minutes. Symptoms can occur in the buttocks, thigh, or calf and often correspond to the level of arterial blockage. While IC can be identified through standard medical history, several validated claudication questionnaires are also utilized in epidemiological studies. Many PAD patients do not exhibit typical IC but rather atypical limb symptoms or no clear symptoms at all. Recognizing asymptomatic PAD is crucial, as patients with PAD, regardless of leg symptoms, have a poorer prognosis and reduced limb function compared to those without PAD. Some patients may also reduce their daily activity to alleviate limb symptoms.⁸ The global prevalence of PAD is approximately 5.6% and often presents atypically in women.⁹ Our study attempted to study the risk from development of PAD using ABI. The ankle-brachial index (ABI) is used to diagnose PAD. It is calculated by dividing the higher of the ankle systolic pressures (either dorsalis pedis or posterior tibial) by the highest brachial systolic pressure from either arm. Under normal blood flow conditions in the lower extremities, the ankle pressure should equal or slightly exceed the arm pressure, resulting in an ABI value of 1.0 or greater.^10,11 An ABI ratio of ≤0.9 indicates the presence of PAD. Compared to women who have had normotensive pregnancies, those with a history of hypertensive pregnancy are at higher risk of developing PAD.⁴ A Chinese study reported a prevalence of around 8% among hypertensive patients compared to 5% among non-hypertensive individuals.¹² An Italian study identified hypertension as the most prevalent risk factor for developing PAD, contrary to other studies suggesting smoking as the primary risk factor.^13,14

We hypothesized that women with a history of hypertension in pregnancy would be more likely to have PAD, emphasizing that PIH is a risk factor for PAD. Compared to women with normotensive pregnancy, women with a history of PIH had greater odds of PAD (3.12 (odds ratio); 0.54 to 17.8 (95% confidence interval), p = 0.199). Due to a very low sample size at five year follow up though odds ration is high, the values are skewed. Although PIH has been identified as a risk factor for PAD (14), there is a lack of studies assessing the prevalence of PAD and whether PIH is a risk factor for PAD among pregnant Indian mothers. Therefore, this study aims to fill this gap in the existing literature and attempts to register the presence of risk for PAD in Indian women with PIH. We recommend larger multicentric tials for establishing the significant risk of PAD in patients with PIH.

Conclusion:

Women with Pregnancy induced hypertension are at higher risk for development of Peripheral artery disease

REFERENCES: 1. Kintiraki E, Papakatsika S, Kotronis G, Goulis DG, Kotsis V. Pregnancy-Induced hypertension. Hormones (Athens). 2015;14(2):211–23. 2. Filippi V, Chou D, Ronsmans C, Graham W, Say L. Levels and Causes of Maternal Mortality and Morbidity. In: Black RE, Laxminarayan R, Temmerman M, Walker N, editors. Reproductive, Maternal, Newborn, and Child Health: Disease Control Priorities, Third Edition (Volume 2) 3. Wu R, Wang T, Gu R, Xing D, Ye C, Chen Y, et al. Hypertensive Disorders of Pregnancy and Risk of Cardiovascular Disease-Related Morbidity and Mortality: A Systematic Review and Meta-Analysis. Cardiology. 2020 Aug 25;145(10):633–47. 4. Hypertension in Pregnancy is a Risk Factor for Peripheral Arterial Disease Decades after Pregnancy - PMC [Internet]. [cited 2024 Jul 5]. 5. Gajjala PR, Sanati M, Jankowski J. Cellular and Molecular Mechanisms of Chronic Kidney Disease with Diabetes Mellitus and Cardiovascular Diseases as Its Comorbidities. Frontiers in Immunology [Internet]. 2015 [cited 2024 Jul 16];6. 6. Slovut DP, Sullivan TM. Critical limb ischemia: medical and surgical management. Vasc Med. 2008 Aug 1;13(3):281–91. 7. Ray JG, Vermeulen MJ, Schull MJ, Redelmeier DA. Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study. Lancet. 2005;366:1797–1803. 8. Aday AW, Matsushita K. Epidemiology of Peripheral Artery Disease and Polyvascular Disease. Circulation Research. 2021 Jun 11;128(12):1818–32. 9. Challenges associated with peripheral arterial disease in women - PMC [Internet]. [cited 2024 Jul 5]. 10. Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. European Heart Journal. 2013 Aug 14;34(31):2436–43. 11. Paraskevas KI, Phillips MJ, Shearman CP. Screening for Peripheral Arterial Disease Using the Ankle-Brachial Index in Diabetic and Other High-Risk Patients: Pros and Cons. Angiology. 2016 Aug 1;67(7):607–9. 12. Prevalence of and risk factors for peripheral arterial disease in the patients with hypertension among Han Chinese - ScienceDirect [Internet]. [cited 2024 Jul 18]. 13. Fowkes FGR, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. The Lancet. 2013 Oct 19;382(9901):1329–40. 14. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis - ScienceDirect [Internet]. [cited 2024 Jul 21].