Renal denervation for hypertension
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Self-reported hypertension prevalence, risk factors, and knowledge among South Africans aged 24 to 40 years old
Although hypertension is a significant public health burden in South Africa (SA), less is known about its prevalence, risk factors, and possible preventative strategies among young adults. We assessed the prevalence, possible risk factors, and knowledge associated with self-reported hypertension among young adults from SA. A cross-sectional online survey was conducted among 1000 young South African adults (24–40 years; 51.0% women). We administered a socio-demographic questionnaire and collected information on measures of socio-economic status (SES) (e.g. asset wealth index), self-reported medical history, and lifestyle risk factors. Furthermore, a modified version of the hypertension evaluation of lifestyle and management questionnaire was used to assess participants’ hypertension knowledge. The overall prevalence of self-reported hypertension was 24.0%, with significant differences between women and men (27.5% and 20.4% respectively, p = 0.033). Only 16.8% of the respondents had good hypertension knowledge. There was a positive association between good knowledge of hypertension and being hypertensive (OR = 1.43 CI:1.23–3.12), monthly blood pressure check-ups (OR = 2.03 CI:1.78–3.23), knowing the side effects of uncontrolled blood pressure (OR = 1.28 CI:1.07–1.89) and having a biological mother with hypertension (OR = 1.79 CI:1.53–2.21). Being employed full-time (OR = 0.74 CI:0.69–0.80), having a higher SES (wealth index 4 (OR = 0.70 CI:0.59–0.97) and 5 (OR = 0.65 CI:0.48–0.81)), exercising 6 to 7 days per week (OR = 0.83 CI:0.71–0.94), and not consuming alcohol at all (OR = 0.73 CI:0.67–0.89), were all found to be protective against hypertension. The high hypertension prevalence, lack of hypertension knowledge, and reported risk factors among this group highlight the need for early robust preventative strategies to mitigate hypertension risk among this population.
Inhibition of sympathetic tone via hypothalamic descending pathway propagates glucocorticoid-induced endothelial impairment and osteonecrosis of the femoral head
Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MPS) daily for 3 days, and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice. Importantly, treatment with a GR inhibitor (RU486) in the PVN promotes the activation of MR and rebalances the ratio of GR and MR, thus effectively boosting sympathetic outflow, as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice. Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head, while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2 (Adrb2) knockout. Furthermore, activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype. Mechanistically, norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via Adrb2-cyclic AMP response element-binding protein (CREB) signaling. Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice. Thus, GC inhibits sympathetic tone via the hypothalamic descending pathway, which, in turn, acts as a mediator of GC-induced ONFH.
Epigenomics and transcriptomics association study of blood pressure and incident diagnosis of hypertension in twins
Hypertension is the most frequent health-related condition worldwide and is a primary risk factor for renal and cardiovascular diseases. However, the underlying molecular mechanisms are still poorly understood. To uncover these mechanisms, multi-omics studies have significant potential, but such studies are challenged by genetic and environmental confounding – an issue that can be effectively reduced by studying intra-pair differences in twins. Here, we coupled data on hypertension diagnoses from the nationwide Danish Patient Registry to a study population of 740 twins for whom genome-wide DNA methylation and gene expression data were available together with measurements of systolic and diastolic blood pressure. We investigated five phenotypes: incident hypertension cases, systolic blood pressure, diastolic blood pressure, hypertension (140/90 mmHg), and hypertension (130/80 mmHg). Statistical analyses were performed using Cox (incident cases) or linear (remaining) regression analyses at both the individual-level and twin pair-level. Significant genes (p < 0.05) at both levels and in both types of biological data were investigated by bioinformatic analyses, including gene set enrichment analysis and interaction network analysis. Overall, most of the identified pathways related to the immune system, particularly inflammation, and biology of vascular smooth muscle cell. Of specific genes, lysine methyltransferase 2 A (KMT2A) was found to be central for incident hypertension, ataxia-telangiectasia mutated (ATM) for systolic blood pressure, and beta-actin (ACTB) for diastolic blood pressure. Noteworthy, lysine methyltransferase 2A (KMT2A) was also identified in the systolic and diastolic blood pressure analyses. Here, we present novel biomarkers for hypertension. This study design is surprisingly rare in the field of hypertension.
Investigation and management of resistant hypertension: British and Irish Hypertension Society position statement
People living with resistant hypertension (RH) are at high risk of adverse cardiovascular events. The British and Irish Hypertension Society has identified suspected RH as a condition for which specialist guidance may improve rates of blood pressure control and help clinicians identify those individuals who may benefit from specialist review. In this position statement we provide a practical approach for the investigation and management of adults with RH. We highlight gaps in the current evidence and identify important future research questions. Our aim is to support the delivery of high-quality and consistent care to people living with RH across the UK and Ireland.
A first-in-human study of quantitative ultrasound to assess transplant kidney fibrosis
Kidney transplantation is the optimal treatment for renal failure. In the United States, a biopsy at the time of organ procurement is often used to assess kidney quality to decide whether it should be used for transplant. This assessment is focused on renal fibrotic burden, because fibrosis is an important measure of irreversible kidney injury. Unfortunately, biopsy at the time of transplant is plagued by problems, including bleeding risk, inaccuracies introduced by sampling bias and rapid sample preparation, and the need for round-the-clock pathology expertise. We developed a quantitative algorithm, called renal H-scan, that can be added to standard ultrasound workflows to quickly and noninvasively measure renal fibrotic burden in preclinical animal models and human transplant kidneys. Furthermore, we provide evidence that biopsy-based fibrosis estimates, because of their highly localized nature, are inaccurate measures of whole-kidney fibrotic burden and do not associate with kidney function post-transplant. In contrast, we show that whole-kidney H-scan fibrosis estimates associate closely with post-transplant renal function. Taken together, our data suggest that the addition of H-scan to standard ultrasound workflows could provide a safe, rapid and easy-to-perform method for accurate quantification of transplant kidney fibrotic burden, and thus better prediction of post-transplant renal outcomes.
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