Introduction: Many medications have an unproven safety profile for use during pregnancy, leading to issues when chronic diseases, such as hypertension and depression, present during pregnancy. The focus of this research programme is to determine whether in utero exposure to antihypertensive and antidepressant medication is associated with increased risk of adverse events at birth, and up to 27 months of age in the child. Methods: Two systematic reviews were performed to identify current published literature and knowledge gaps. Following this, using Scottish healthcare data, a cohort of 268,711 children born 2010-2014 were identified. Following cleaning of the data, multiple imputation was used to account for missing values. Poisson, linear and multinomial regressions were performed to identify the relationship between in utero medication exposure and child outcomes. Results: In utero antihypertensive exposure was associated with preterm birth, low birth weight, small for gestational age, but not developmental issues. However, untreated hypertension was associated with low birth weight, preterm birth, and small for gestational age. In utero antidepressant exposure was associated with preterm birth, low birth weight, small for gestational age, preeclampsia, having a special needs indicator at 10 days and 6-8 weeks post-birth, developmental issues at 27 months Conclusions: This research programme identified several adverse outcomes following in utero exposure to antihypertensive and antidepressant medication.

Many older patients are not being aggressively managed for hypertension. Healthcare providers are often hesitant to start or even aggressively titrate antihypertensive medication, especially in the aged. Multiple studies have demonstrated that morbidity and mortality can be significantly reduced by appropriate intervention in all age groups. There are some clinical situations, however, where the provider must approach cautiously, such as in patients with a wide pulse pressure or those with a propensity toward adverse reactions. The data are clear that in the United States, undertreatment, rather than overtreatment, appears to be the issue. This article reviews studies that support the aggressive treatment of hypertension. The nuances of aging, which often influence the healthcare provider's treatment decisions, are also discussed. Suggestions for reasonable approaches to these difficult cases will be considered.

The aim of this thesis was to investigate the effect of antihypertensive therapy on vascular function and placental markers in hypertensive disorders in pregnancy (HTD). We prospectively studied 208 women at the Homerton and University College London Hospitals. Vascular and serum markers were measured in 80 with HTD [51 pre-eclampsia (PE), 29 gestational hypertension (GH)] and 80 normotensive controls. The same markers were measured in placental samples from another 48 women (14 PE, 10 GH, 24 controls). Pulse wave analysis indices [augmentation pressure (AP) and augmentation index at heart rate 75/minute (Aix-75)], serum and placental concentrations of soluble fms-like tyrosine-kinase-1 (sFlt-1), soluble endoglin (sEng), placental growth factor (PIGF), vascular endothelial growth factor (VEGF), inhibin A, activin A, and uterine artery Doppler were measured before, and 24-48 hours after, initiating antihypertensive therapy. The three study groups were compared using ANOVA multiple comparisons with Bonferroni post hoc testing. Marker levels before and after antihypertensives were compared using paired t-test. In both pre-eclampsia (P < 0.0001) and gestational hypertension (P < 0.05), serum sFlt-1 was increased and PIGF reduced (P < 0.001) compared to controls. Serum sEng levels were also increased in pre-eclampsia. Placental sFlt-1 and sEng were significantly higher (P < 0.0001), and PIGF lower (P = 0.008), in pre-eclampsia compared to controls and gestational hypertension. Antihypertensive therapy was associated with a significant fall in serum and placental sFlt-1 and sEng in pre-eclampsia only (P < 0.05). In pre-eclampsia, but not gestational hypertension, treatment was associated with significantly (P < 0.05) lower serum and placental inhibin A and activin A. In women with pre-eclampsia or gestational hypertension, both AP (P < 0.0001 and P < 0.05) and Aix-75 (P < 0.0001 and P < 0.001) were significantly higher than controls. Antihypertensive therapy resulted in a significant fall in both AP and Aix-75 in pre-eclampsia only (P < 0.0001). Anti hypertensive drugs may have an effect on the pathophysiology of pre-eclampsia other than their known anti hypertensive action.

Background: A major problem in the treatment of human hypertension is the late diagnosis of hypertension and, hence, the delayed start of treatment. Very often, hypertension has existed for a long time and cardiac damage has already developed. Therefore, we tested whether late- onset antihypertensive treatment is effective in lowering blood pressure (BP) and in reducing or even preventing left ventricular hypertrophy and fibrosis. Methods: Twenty-one male 60-week-old spontaneously hypertensive rats (SHR) were included. Fourteen rats received oral treatment with captopril (CAP) either as monotherapy or combined with nifedipine (CAP + NIF) over 22 weeks. Seven untreated SHR served as controls. We examined the therapeutic effects on BP, heart weight and histological and biochemical markers of left ventricular remodeling and fibrosis. Results: At 82 weeks of age, BP was reduced in the CAP and CAP + NIF groups by 44 and 51 mmHg, respectively (p < 0.001), but not in untreated controls. Despite the late therapy start, cardiac hypertrophy and fibrosis were attenuated compared to controls. Both treatments reduced heart weight by 1.2 mg/g (25%, p = 0.001) and collagens I and III by 66% and 60%, respectively (p < 0.001), thus proving nearly equivalent cardioprotective efficacy. Conclusion: These data clearly emphasize the benefit of antihypertensive treatment in reducing BP and mitigating the development of cardiac amage even when treatment is started late in life.

Background: A major problem in the treatment of human hypertension is the late diagnosis of hypertension and, hence, the delayed start of treatment. Very often, hypertension has existed for a long time and cardiac damage has already developed. Therefore, we tested whether lateonset antihypertensive treatment is effective in lowering blood pressure (BP) and in reducing or even preventing left ventricular hypertrophy and fibrosis. Methods: Twenty-one male 60-week-old spontaneously hypertensive rats (SHR) were included. Fourteen rats received oral treatment with captopril (CAP) either as monotherapy or combined with nifedipine (CAP + NIF) over 22 weeks. Seven untreated SHR served as controls. We examined the therapeutic effects on BP, heart weight and histological and biochemical markers of left ventricular remodeling and fibrosis. Results: At 82 weeks of age, BP was reduced in the CAP and CAP + NIF groups by 44 and 51 mmHg, respectively (p < 0.001), but not in untreated controls. Despite the late therapy start, cardiac hypertrophy and fibrosis were attenuated compared to controls. Both treatments reduced heart weight by 1.2 mg/g (25%, p = 0.001) and collagens I and III by 66% and 60%, respectively (p < 0.001), thus proving nearly equivalent cardioprotective efficacy. Conclusion: These data clearly emphasize the benefit of antihypertensive treatment in reducing BP and mitigating the development of cardiac damage even when treatment is started late in life.