Journal of internal medicine
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Essential hypertension is a complex trait where the underlying aetiology is not completely understood. Left untreated it increases the risk of severe health complications including cardiovascular and renal disease. It is almost 15 years since the first genome-wide association study for hypertension, and after a slow start there are now over 1000 blood pressure (BP) loci explaining ∼6% of the single nucleotide polymorphism-based heritability. ⋯ Drug re-purposing opportunities, including SLC5A1 and canagliflozin (a type-2 diabetes drug), are also being identified. In this review, we present key studies from the past, highlight current avenues of research and look to the future focusing on gene discovery, epigenetics, gene-environment interactions, GRSs and drug discovery. We evaluate limitations affecting BP genetics, including ancestry bias and discuss streamlining of drug target discovery and applications for treating and preventing hypertension, which will contribute to tailored precision medicine for patients.
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Exposure to cadmium (Cd) via food and smoking is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood and urine levels of Cd are established biomarkers of exposure. ⋯ There is strong evidence that Cd causes ASCVD above a suggested exposure level via mechanisms in early as well as the late stages of atherosclerotic disease.
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Observational studies show that physical activity is strongly associated with a reduced risk of premature mortality and major non-communicable diseases. We reviewed to which extent these associations have been confirmed in randomized controlled trials (RCTs) for the outcomes of mortality, cardiovascular disease (CVD), type 2 diabetes (T2D), and fracture. The results show that exercise does not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants. ⋯ Thus, additional large trials would be of value, especially with fracture as the primary outcome. In conclusion, according to current RCT evidence, exercise can prevent T2D assuming it is combined with dietary intervention. However, the current evidence shows that exercise does not prevent premature mortality or CVD, with inconsistent evidence for fractures.
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Peripheral arterial disease (PAD) and coronary artery disease (CAD) are both caused by atherosclerosis. Serum lipids and lipoproteins are predictive of the development of atherosclerosis but it is not clear if they differ in the two manifestations, PAD and CAD. We tested whether a more detailed characterization of the lipid and lipoprotein patterns of PAD and CAD allows a clear differentiation between the two atherosclerotic phenotypes. ⋯ The present study clearly suggests that PAD and CAD differ in terms of their ceramide- and phosphatidylcholine-based lipid patterns but not in lipoprotein characteristics.
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Growth hormone (GH) deficiency develops early in patients with hypothalamic-pituitary disorders and is therefore common among these patients. GH deficiency in adults is associated with increased morbidity, increased body fat mass, abdominal obesity, dyslipidaemia, reduced exercise capacity, impaired cardiac function as well as reduced self-reported well-being and impaired quality of life. Since recombinant human GH became available as replacement therapy more than 25 years ago, randomised controlled trials and long-term studies, together with meta-analyses, have shown improved outcomes in adult patients with hypopituitarism receiving GH. ⋯ The increased interest in GH deficiency in adults with hypothalamic-pituitary disorders has also contributed to the identification of other factors of importance for an outcome such as the replacement of other pituitary hormone deficiencies, and the management of the underlying hypothalamic-pituitary disease, most commonly a pituitary tumour. In this narrative review, we summarize the burden of GH deficiency in adults with hypopituitarism, the impact of GH replacement on the outcome, as well as safety. Based on currently available data, GH replacement should be considered routine management of adults with hypopituitarism.