Sex differences in hypertension and other cardiovascular diseases

No abstract available

Blood pressure targets in the elderly

No abstract available

Diabetic nephropathy: early detection and therapeutic strategies

The increasing global prevalence of diabetes poses a huge challenge to health services. The diagnosis is accompanied by a reduction in life expectancy, primarily due to cardiovascular disease which is inextricably linked to microvascular complications such as diabetic nephropathy (DN). Microalbuminuria (MA) is generally accepted as the primary clinical hallmark of DN, but despite widespread prescribing of agents blocking the renin angiotensin aldosterone system (RAAS) in these patients many continue to progress towards end-stage renal disease (ESRD). Clinical trials evaluating early initiation of RAAS blocking agents in untargeted, nonalbuminuric diabetic patients have shown potential for delaying disease progression but these effects are generally counterbalanced by side effects and adverse events associated with these therapies. Discovery of novel biomarkers to identify individuals at highest risk of DN who would stand to benefit most from targeted preclinical intervention would be a significant step towards implementation of personalised medicine in this population. One technique which shows promise is proteomics, based on the concept of separation and quantification of peptides in a biological sample to produce a disease-specific pattern. A panel of 273 urinary peptides (CKD273) has been shown to have potential for identification of nonalbuminuric diabetic patients who are at risk of progression to overt DN. However, many such novel biomarkers are described in the literature and to date none have successfully made the transition from research studies to routine clinical practice. In order to be considered for clinical implementation novel biomarkers are required to be subject to a rigorous evaluation process. In brief there are several key steps beginning with proof-of-concept studies; progressing through validation in independent populations to demonstration of incremental value beyond the current guideline-endorsed tests; thereafter proof of clinical applicability in determining treatment strategies and cost-effectiveness are required. The work contained within this thesis is designed to address each of these aspects with regard to use of the CKD273 proteomic panel as a biomarker for early detection of DN

The future of "omics" in hypertension

Despite decades of research and clinical practice the pathogenesis of hypertension remains incompletely understood and blood pressure is often suboptimally controlled. Omics technologies allow the description of a large number of molecular features and have the potential to identify new factors that contribute to blood pressure regulation and how they interact. In this review we will focus on the potential of genomics, transcriptomics, proteomics and metabolomics and explore their role in unravelling the pathophysiology and diagnosis of hypertension; prediction of organ damage and treatment response; and monitoring of treatment effect. Substantial progress has been made in the area of genomics where genome-wide association studies have identified more than 50 blood pressure-related single nucleotide polymorphisms and sequencing studies especially in secondary forms of hypertension have discovered novel regulatory pathways. In contrast, other omics technologies, despite their ability to provide detailed insights into the physiological state of an organism, have only more recently demonstrated their impact on hypertension research and clinical practice. The majority of current proteomic studies focuses on organ damage due to hypertension and may have the potential to understand the link between blood pressure and organ failure but also serve as biomarker for early detection of cerebrovascular or coronary disease. Examples include signatures for early detection of left ventricular dysfunction or albuminuria. Metabolomic studies have potential to integrate environmental and intrinsic factors and are particularly suited to monitor the response to treatment. We will discuss examples of omics studies in hypertension and explore the challenges related to these novel technologies

Vascular biomedicine in an era of chronic disease and multimorbidity

It is increasingly common that patients present with more than one disease and that diseases are chronic in nature. Cardiovascular conditions such as hypertension, heart failure and stroke, renal diseases and cardiometabolic conditions such as diabetes are prime examples of chronic diseases which pose major challenges in contemporary healthcare provision. The complex features of multimorbidity call for precision medicine approaches that take comorbidity and chronicity into account. The research basis of chronic disease and multimorbidity, however, is currently in its infancy. This applies to all domains including basic, translational and clinical science. In this article we call for development of new models, smarter use of existing models and better characterisation of vascular and cardiovascular phenotypes in studies not directly related to cardiovascular diseases. This has the potential to further improve the quality of translational research, papers in journals such as Clinical Science and ultimately translate into better patient care

Use of biomarkers in the evaluation and treatment of hypertensive patients

The current definition of hypertension is based on blood pressure values, and blood pressure also drives treatment decisions, is the most important treatment monitoring tool and helps estimating risk of hypertension related organ damage. In an era of precision medicine additional biomarkers are needed in the diagnosis and management of patients with hypertension. In this review we outline the areas in which functional, imaging and circulating biomarkers could help in a more individualised definition of hypertension and associated risk. We will cover biomarkers for diagnosis; of pathophysiology and prediction of hypertension; response to treatment, organ damage; and to monitor treatment. A clear focus is on the vasculature, the heart and the kidneys, whereas we see a need to further develop biomarkers of cerebral function in order to diagnose cognition deficits and monitor changes in cognition in the future to support addressing the growing burden of hypertension associated vascular dementia

Is there a role for proteomics in diabetic renal disease?

No abstract available

Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis

Background: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. Methods: We conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966–2014), EMBASE (1947–2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults. Results: Nineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (−5.7 [−9.0, −2.3] mmHg), diastolic blood pressure (−1.7 [−3.4, −0.1] mmHg) and glomerular filtration rate (−3.2 [−5.4, −1.0] mL/min/1.73 m2 ). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse. Conclusions: Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit

Systematic review of micro-RNA expression in pre-eclampsia identifies a number of common pathways associated with the disease

Background: Pre-eclampsia (PE) is a complex, multi-systemic condition of pregnancy which greatly impacts maternal and perinatal morbidity and mortality. MicroRNAs (miRs) are differentially expressed in PE and may be important in helping to understand the condition and its pathogenesis. Methods: Case-control studies investigating expression of miRs in PE were collected through a systematic literature search. Data was extracted and compared from 58 studies to identify the most promising miRs associated with PE pathogenesis and identify areas of methodology which could account for often conflicting results. Results: Some of the most frequently differentially expressed miRs in PE include miR-210, miR-223 and miR-126/126* which associate strongly with the etiological domains of hypoxia, immunology and angiogenesis. Members of the miR-515 family belonging to the imprinted chromosome 19 miR cluster with putative roles in trophoblast invasion were also found to be differentially expressed. Certain miRs appear to associate with more severe forms of PE such as miR-210 and the immune-related miR-181a and miR-15 families. Patterns of miR expression may help pinpoint key pathways (e.g. IL-6/miR-223/STAT3) and aid in untangling the heterogeneous nature of PE. The detectable presence of many PE-associated miRs in antenatal circulatory samples suggests their usefulness as predictive biomarkers. Further progress in ascertaining the clinical value of miRs and in understanding how they might contribute to pathogenesis is predicated upon resolving current methodological challenges in studies. These include differences in diagnostic criteria, cohort characteristics, sampling technique, RNA isolation and platform-dependent variation in miR profiling. Conclusion: Reviewing studies of PE-associated miRs has revealed their potential as informants of underlying target genes and pathways relating to PE pathogenesis. However, the incongruity in results across current studies hampers their capacity to be useful biomarkers of the condition