Oxygen therapy in premature low birth weight infants is associated with capillary loss and increases in blood pressure: a pilot study

Low birth weight (LBW) and premature birth are known risk factors for future cardiovascular disease and in particular essential hypertension (EH). Capillary rarefaction (CR) is an established hallmark of EH and is known to occur in individuals with a history of LBW. We previously reported that LBW infants do not have CR at birth but rather increased capillary density (CD). We hypothesized that LBW infants undergo a process of accelerated CR in early life, triggered in part by oxygen therapy. We studied 26 LBW infants, of whom 10 infants received oxygen therapy, and compared them to 14 normal birth weight (NBW) infants. We measured CD at 1, 5 and 10 days after birth and again after 40 weeks adjusted gestational age equivalent to birth at full term. We confirmed that LBW infants had higher CD at birth compared to NBW infants and found that significant structural CR occurred at term age in LBW infants who had received oxygen therapy (mean difference −22 capillaries/field, p = 0.007) and in those who did not receive oxygen therapy (mean difference −29 capillaries/field, p < 0.001) compared to baseline at birth. Both LBW groups showed a significant rise in BP at 40 weeks adjusted term age and the rise in systolic (mean difference 24 mm Hg, p < 0.0001) and diastolic BP (mean difference 14 mm Hg, p < 0.001) was more pronounced in the oxygen treated group compared to the nonoxygen group (mean difference 14 mm Hg, p = 0.043 and mean difference = 9 mm Hg p = 0.056 respectively). In conclusion, oxygen therapy in premature LBW infants may induce significant increases in their BP in early life

Effects of candesartan versus amlodipine on capillary rarefaction, pulse wave velocity, and central blood pressure in patients with essential hypertension

Background: A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension and play a role in increasing Blood Pressure (BP). The aim of this trial was to assess in a randomized, double blind, design the effects of treatment of hypertension with candesartan versus amlodipine on microvascular rarefaction and other indices of vascular function. Methods: We recruited twenty-two individuals with mild-to-moderate hypertension. After a 2-week placebo run-in period, patients who remained hypertensive (≥140/90 mmHg) were randomized to 8-weeks treatment with Candesartan tablets 8mg daily (with forced titration to 16mg) or Amlodipine tablets 5mg daily (with forced titration to 10mg). The capillary microcirculation was studied using CapiScope system CAM1. Pulse wave velocity, central BP and aortic Augmentation Index were also measured. Results: We observed significant reductions in brachial BP, and central BP after 4 and 8 weeks treatment with either candesartan or amlodipine but there was no significant effect on basal (functional) or maximal (structural) capillary densities, or pulse wave velocity. Conclusion: Eight weeks treatment of hypertension with either amlodipine or candesartan significantly reduced brachial and central BP but was not sufficient to induce a regression in functional or structural microvascular abnormalities

Familial hypercholesterolaemia: identification and management. Evidence reviews for case-finding, diagnosis and statin monotherapy

This guideline covers identifying and managing familial hypercholesterolaemia (FH), a specific type of high cholesterol that runs in the family, in children, young people and adults. It aims to help identify people at increased risk of coronary heart disease as a result of having FH. In November 2017, we reviewed the evidence for case finding and diagnosis, identification using cascade testing, and management using statins. We amended recommendations in sections 1.1, 1.2 and 1.3

Capillary Remodeling in Infants Born to Hypertensive Pregnancy: Pilot Study

BACKGROUND Capillary rarefaction is pathognonnonic of essential hypertension. We have previously shown significant capillary rarefaction in normotensive adult offspring of hypertensive parents, suggesting a familial predisposition in which capillary rarefaction represents a primary vascular abnormality that antedates the onset of sustained elevation of blood pressure (BP). We have recently reported that low-birth weight (LBW) infants, born at term or preterm, to normotensive mothers do not have capillary rarefaction at birth. We hypothesized that infants born to mothers with hypertensive disorders of pregnancy (HDP) would have significant capillary rarefaction at birth when compared to infants of normotensive mothers. METHODS We studied 22 infants born to hypertensive mothers and compared them to 40 normal birth weight infants born at term to normotensive mothers. We used orthogonal polarized spectroscopy to measure basal (i.e., functional) and maximal (i.e., structural) skin capillary densities according to a well-validated protocol. RESULTS We found that term infants born to hypertensive mothers had significantly lower maximal capillary density (MCD) (mean difference of -5.0 capillaries/mm(2); P < 0.05). However, preterm infants with LBW born to hypertensive mothers tended to have higher basal and maximal skin capillary densities compared with term infants. CONCLUSIONS While the results in term infants are consistent with our belief that capillary rarefaction in essential hypertension is likely to be a primary vascular abnormality, the results in preterm infants may suggest that the intrauterine environment may exert some influences on the remodeling of the microcirculation which may delay the onset of capillary rarefaction in these infants

Late effects of hypertensive disorders of pregnancy on central blood pressure, microcirculation and cardiovascular disease: a cross-sectional case control study

Objective: The Inter-arm blood Pressure difference Individual Patient Data (INTERPRESS-IPD) Collaboration recently demonstrated, based on data from over 57,000 records, that an inter-arm difference in systolic blood pressure (IAD) is an independent risk marker for cardiovascular events after adjustment for Framingham or QRISK2 scores. This approach offers improved risk prediction through reclassification of individuals across risk categories and can result in initiation of treatment for primary prevention of cardiovascular disease in those close to current pharmaceutical intervention thresholds. The aim of this study was to model this approach of adjusting cardiovascular risk prediction scores for IAD in a typical primary care population. Design and method: Individuals aged 45–75 years, free of cardiovascular disease, had bilateral blood pressure measured three times, simultaneously, during National Health Service (NHS) Health Checks in one rural general practice in Devon, England. QRISK2 scores were calculated as part of the Health Check process, Framingham risk scores were calculated during analysis with Stata v15.0. Framingham and QRISK2 risk scores were adjusted by taking account of hazard ratios for IAD derived from our INTERPRESS-IPD analyses. Results: Complete data existed for 334 participants [mean (standard deviation): age 57.4 (9.3), systolic/diastolic blood pressure 132 (14)/79 (8.5)]. Mean Framingham and QRISK2 scores were 10.7 (8.1) and 8.0 (6.9), respectively before adjustment for IAD, and 11.1 (8.5) and 8.2 (7.1) afterwards (see figure). Overall, 10 (3%) participants were reclassified from below to above either the 10% or 20% Framingham risk thresholds, and 2 (1%) individuals were reclassified across the corresponding QRISK2 thresholds. For individuals with initial risk scores of 8% to 9.9%, 7/38 (18%) were reclassified to a Framingham risk above 10% and 2/35 (6%) to a QRISK2 score above 10%. Conclusions: Our findings confirm that systolic IADs can be applied to refine cardiovascular risk estimates in a UK primary care population. By taking account of systolic IAD, individual decisions on interventions for primary prevention of cardiovascular disease can be personalised, and could facilitate targeting of treatment to those at greater than average cardiovascular risk