Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although primary chronic hypertension (HTN) is increasingly common in adolescence, secondary forms of HTN are more common among children. Primary HTN is associated with being overweight and/or a positive family history of HTN. Carotid intima-media thickness, a known risk factor for atherosclerosis is frequent in both adults and children with HTN and other associated cardiovascular (CV) risk factors including obesity, dyslipidemia, diabetes and chronic kidney disease. Left ventricular (LV) hypertrophy is also a common finding in children and adolescents with newly diagnosed HTN. Children with certain medical conditions such as congenital heart disease and Kawasaki disease can develop premature atherosclerosis heart disease that may lead to coronary heart disease and heart failure. Life-style interventions are recommended for all children with HTN, with pharmacologic therapy added for symptomatic children based on the presence of co-morbidities. As an example, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blocker and/or calcium channel blockers would be best for children with CV risk factors such as diabetes or renal disease, whereas an ACE inhibitor in combination with a beta-blocker and diuretics including spironolactone are recommended for patients with heart failure and reduced LV ejection fraction. This report will summarize new developments in the management of pediatric HTN complicated with CV disease and heart failure and will address the appropriate antihypertensive therapy that could potentially reduce the future burden of adult CV disease.
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PMID:Management of hypertension in children with cardiovascular disease and heart failure. 2479 Nov 85

Despite current practice, patients with chronic kidney disease (CKD) are at increased risk of progression to end-stage renal disease and cardiovascular events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin-angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting enzyme inhibitors but were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, one such agent (omapatrilat) showed promise of NEP/RAS inhibition in treating CKD in animal models, producing greater reductions in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with isolated RAS inhibition. A new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in hypertension and HF. In CKD, HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that ARNi could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of cardiovascular disease. LCZ696 is now being studied in a CKD population.
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PMID:Neprilysin inhibition in chronic kidney disease. 2514 14

The renin-angiotensin-aldosterone system (RAAS) is an enzymatic cascade functioning in a paracrine and autocrine fashion. In animals and humans, RAAS intrinsic to tissues modulates food intake, metabolic rate, adiposity, insulin sensitivity, and insulin secretion. A large array of observations shows that dysregulation of RAAS in the metabolic syndrome favors type 2 diabetes. Remarkably, angiotensin-converting enzyme inhibitors, suppressing the synthesis of angiotensin II (ANG II), and angiotensin receptor blockers, targeting the ANG II type 1 receptor, prevent diabetes in patients with hypertensive or ischemic cardiopathy. These drugs interrupt the negative feedback loop of ANG II on the RAAS cascade, which results in increased production of angiotensins. In addition, they change the tissue expression of RAAS components. Therefore, the concept of a dual axis of RAAS regarding glucose homeostasis has emerged. The RAAS deleterious axis increases the production of inflammatory cytokines and raises oxidative stress, exacerbating the insulin resistance and decreasing insulin secretion. The beneficial axis promotes adipogenesis, blocks the production of inflammatory cytokines, and lowers oxidative stress, thereby improving insulin sensitivity and secretion. Currently, drugs targeting RAAS are not given for the purpose of preventing diabetes in humans. However, we anticipate that in the near future the discovery of novel means to modulate the RAAS beneficial axis will result in a decisive therapeutic breakthrough.
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PMID:Modulation of glucose metabolism by the renin-angiotensin-aldosterone system. 2556 75

Pulmonary hypertension due to left heart disease (PH-LHD) frequently complicates heart failure with reduced ejection fraction (HFrEF). Specific therapies for PH have not offered an advantage in patients with PH-LHD. The combined angiotensin receptor blocker-neprilysin inhibitor (ARNI), sacubitril/valsartan, is a novel therapy that can increase levels of natriuretic peptides (NPs). The resulting action on natriuresis and vasodilation may play an important role in the reduction of pulmonary pressures. Here, we report how the use of ARNI in two patients with HFrEF has resulted in an improvement in PH and, consequently, in clinical status and prognosis. <Learning objective: Sacubitril/valsartan (ARNI) is the newest neurohormonal agent approved for therapy in heart failure with reduced ejection fraction (HFrEF). Pulmonary hypertension (PH) due to left heart disease (PH-LHD) is frequent in patients with HFrEF and is associated with a reduced functional class and poor prognosis. The use of ARNI has been associated with a relevant reduction in pulmonary pressures in two cases of PH-LHD.>.
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PMID:Reduction in pulmonary artery pressures with use of sacubitril/valsartan. 3171 42


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