426 research outputs found

    Hypertension guidelines: is it time to reappraise blood pressure thresholds and targets?

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    Genomics and precision medicine for clinicians and scientists in hypertension

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    The role of renal transporters and novel regulatory interactions in the TAL that control blood pressure

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    Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year (98). Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney's reabsorption of sodium (Na+) relies on sequential actions at various segments along the nephron. When the distal segments of the nephron fail to regulate Na+, the effects on Na+ homeostasis are unfavourable. We propose that the specific nephron region where increased active uptake occurs as a result of variations in Na+ reabsorption is at the thick ascending limb of the loop of Henle (TAL). The purpose of this review is to urge the consideration of the TAL that contributes to the pathophysiology of salt sensitive HTN. Further research in this area will enable development of a therapeutic application for targeted treatment

    Platelet Cytosolic Free Calcium and Echocardiographic Left Ventricular Mass in Essential Hypertension and Primary Hyperparathyroidism

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    Force development in cardiac and vascular muscle is directly related to the concentration of calcium ions in the cytosol. Sustained hypertension is predominantly maintained by an increase in total peripheral resistance and attention has therefore focused on the possibility that changes in intracellular calcium in myocytes of resistance vessels are important in the pathogenesis of essential hypertension in man. Apart from vascular tone, free calcium in cells also stimulates cell proliferation and growth and increased concentrations of calcium ions in cardiac and vascular smooth muscle could mediate the hypertrophy that characteristically occurs in response to an increase in wall tension

    Thyroid stimulating hormone (TSH) ≥2.5mU/l in early pregnancy: prevalence and subsequent outcomes

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    Objective: There remains controversy over how women with abnormal thyroid function tests in pregnancy should be classified. In this study we assessed the proportion of women with thyroid stimulating hormone (TSH) ≥ 2.5 mU/l in a large obstetric cohort, and examined how many have gone on to develop thyroid disease in the years since their pregnancy. Study design: 4643 women were recruited and samples taken in early pregnancy between 2007 and 2010. Thyroid function tests were analysed in 2014; in women with raised TSH computerised health records and prescription databases were used to identify thyroid disease detected since pregnancy. Results: 58 women (1.5%) had a TSH over 5 mU/l and 396 women (10.3%) had TSH between 2.5 and 5 mU/l. Women with TSH > 5mU/l delivered infants of lower birthweight than those with TSH < 2.5 mU/l; there were no other differences in obstetric outcomes between the groups. Of those who have had thyroid tests since their pregnancy, 78% of those with TSH > 5 mU/l and 19% of those with TSH between 2.5 and 5 mU/l have gone on to be diagnosed with thyroid disease. Conclusions: Using a TSH cut-off of 2.5 mU/l in keeping with European and US guidelines means that over 12% of women in this cohort would be classified as having subclinical hypothyroidism. Treatment and monitoring of these women would have major implications for planning of obstetric services

    Case of severe hypertension and nephrotic range proteinuria

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    Genome-Wide Association Studies of Hypertension: Light at the End of the Tunnel

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    Despite its significant genetic component, the study of hypertension by genome-wide association presents more challenges than other common complex diseases. Its high prevalence, heterogeneity, and somewhat unclear definition are the challenges that need to be overcome on one hand. On the other hand, there are issues of small effect sizes and pleiotropism that are not specific to hypertension alone but nonetheless magnify the problems of genetic dissection when coupled with phenotypic misclassification. We discuss issues of study design and summarise published genome-wide association studies (GWASs) of hypertension and blood pressure. With careful study design and analysis success is possible, as demonstrated by the recent large-scale studies. Following these, there is still further scope to advance the field through high fidelity phenotyping and deep sequencing

    Joint editorial for the International Society of Hypertension guidelines

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    Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders

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    Major depressive and bipolar disorders predispose to atherosclerosis, and there is accruing data from animal model, epidemiological, and genomic studies that commonly used antihypertensive drugs may have a role in the pathogenesis or course of mood disorders. In this study, we propose to determine whether antihypertensive drugs have an impact on mood disorders through the analysis of patients on monotherapy with different classes of antihypertensive drugs from a large hospital database of 525 046 patients with follow-up for 5 years. There were 144 066 eligible patients fulfilling the inclusion criteria: age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days. The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641 685 person-years of follow-up). Patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had the lowest risk for mood disorder admissions, and compared with this group, those on β-blockers (hazard ratio=2.11; [95% confidence interval, 1.12–3.98]; P=0.02) and calcium antagonists (2.28 [95% confidence interval, 1.13–4.58]; P=0.02) showed higher risk, whereas those on no antihypertensives (1.63 [95% confidence interval, 0.94–2.82]; P=0.08) and thiazide diuretics (1.56 [95% confidence interval, 0.65–3.73]; P=0.32) showed no significant difference. Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and β-blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders
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