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)

Previous Icelandic studies reported that single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) region and the 5-lipoxygenase activating protein ALOX5AP were associated with ischaemic stroke, whereas other studies reported ambiguous findings. We examined 932 ischaemic stroke patients from a Swedish population-based stroke register, and 396 control subjects. We assessed possible associations between ischaemic stroke and nine preselected SNPs in the chromosome regions of the PDE4D gene, including rs12188950 (SNP45) and rs3887175 (SNP39); the ALOX5AP gene, including rs17222814 (SG13S25) and the promoter region of the MHC class II transactivator, MHC2TA. The T allele of SNP45 showed negative association with ischaemic stroke (odds ratio, OR=0.72; 95% confidence interval (CI): 0.58-0.91; P=0.0055). Among hypertensive subjects, this influence of the T allele of SNP45, and the T allele of SNP39, were more pronounced (with OR=0.52; 95% CI: 0.37-0.73; P=0.0001 and OR=0.57; 95% CI: 0.41-0.79; P=0.0007, respectively). These SNPs also interacted with hypertension with a relative excess risk due to interaction of -1.66 (P=0.0002) for SNP45 and -1.65 (P=0.0005) for SNP39. The P-values remained significant after correction for multiple testing. Among nonhypertensives, the A allele of SG13S25 indicated increased stroke risk (OR=1.82; 95% CI: 1.21-2.74; P=0.0039; not significant after Bonferroni correction). SNP45 was associated with ischaemic stroke even when controlling for hypertension, diabetes, heart disease and smoking. Our meta-analysis of 13 studies (including ours) showed no overall influence of SNP45 on ischaemic stroke. However, the 13 studies may differ because of nonrandom causes, as suggested by the heterogeneity test (P=0.042). This might support previously undetected mechanisms causing fluctuating ischaemic stroke risk.
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PMID:Ischaemic stroke in hypertensive patients is associated with variations in the PDE4D genome region. 1839 40

A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will develop pulmonary arterial hypertension (PAH) if left untreated. Persistent exposure of the pulmonary vasculature to increased blood flow, as well as increased pressure, may result in pulmonary obstructive arteriopathy, which leads to increased pulmonary vascular resistance that, if it approaches or exceeds systemic resistance, will result in shunt reversal. Eisenmenger's syndrome, the most advanced form of PAH associated with CHD, is defined as CHD with an initial large systemic-to-pulmonary shunt that induces severe pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis. The histopathological and pathobiological changes seen in patients with PAH associated with congenital systemic-to-pulmonary shunts, such as endothelial dysfunction of the pulmonary vasculature, are considered similar to those observed in idiopathic or other associated forms of PAH. A pathological and pathophysiological classification of CHD with systemic-to-pulmonary shunt leading to PAH has been developed that includes specific characteristics, such as the type, dimensions and direction of the shunt, extracardiac abnormalities and repair status. A clinically oriented classification has also been proposed. The prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Western countries has been estimated to range between 1.6 and 12.5 cases per million adults, with 25-50% of this population affected by Eisenmenger's syndrome. Clinically, Eisenmenger's syndrome presents with multiple organ involvement, with progressive deterioration of function over time. The signs and symptoms of Eisenmenger's syndrome in the advanced stages include central cyanosis, dyspnoea, fatigue, haemoptysis, syncope and right-sided heart failure. Survival of patients with Eisenmenger's syndrome is clearly less than that of the general population, but appears to be better than that of patients with idiopathic PAH in a comparable functional class. The treatment strategy for patients with PAH associated with congenital systemic-to-pulmonary shunts and, in particular, those with Eisenmenger's syndrome is based mainly on clinical experience rather than being evidence based. General measures include recommendations for physical activity, pregnancy, infections, air travel, exposure to high altitudes and elective surgery, and that psychological assistance be provided as necessary. Phlebotomies are required only when hyperviscosity of the blood is evident, usually when the haematocrit is >65%. The use of supplemental oxygen therapy is controversial and it should be used only in patients in whom it produces a consistent increase in arterial oxygen saturation. Oral anticoagulant treatment with warfarin can be initiated in patients with pulmonary artery thrombosis and absent, or only mild, haemoptysis. The following three classes of drugs targeting the correction of abnormalities in endothelial dysfunction have been approved recently for the treatment of PAH: (i) prostanoids; (ii) endothelin receptor antagonists; and (iii) phosphodiesterase-5 inhibitors. The efficacy and safety of these compounds have been confirmed in uncontrolled studies in patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts, as well as in patients with Eisenmenger's syndrome. One randomized controlled trial reported favourable short- and long-term outcomes of treatment with the orally active dual endothelin receptor antagonist bosentan in patients with Eisenmenger's syndrome. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation are options for Eisenmenger's syndrome patients with a poor prognosis. A treatment algorithm based on the one used in the treatment of PAH patients is proposed for patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome.
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PMID:Management of pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome. 1848 98

The development of drugs for lowering pressures in pulmonary arterial hypertension (PHT) has provided possible therapeutic application in patients with pulmonary hypertension associated with congenital heart disease (CHD). Prostanoids, both nonselective and selective endothelin-receptor antagonists and phosphodiesterase-V inhibitors have been used for this purpose. The efficacy of these drugs - from different classes of bioactivity - in this context have been shown in several studies. However, the long-term effects of drug treatment on prognosis and course of PHT have not yet been adequately investigated. The current status of drug treatment of PHT in patients with CHD is reviewed in this article.
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PMID:[Pharmacological treatment of pulmonary hypertension in patients with congenital heart disease]. 1881 99

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging men and can significantly affect quality of life. Men with bothersome LUTS/BPH often present with various other age-related conditions, including sexual dysfunction, heart disease, hypertension, diabetes, and the metabolic syndrome, which can complicate management decisions. Therefore, healthcare providers should be familiar with first-line treatment options for LUTS/BPH and their differing safety profiles, particularly with respect to cardiovascular and sexual function side effects. This article presents a review of first-line medical therapy options for managing aging men with LUTS/BPH and patient considerations when evaluating and selecting these therapies, with a focus on the clinical efficacy and cardiovascular and sexual function safety profiles of the uroselective alpha1-adrenergic receptor antagonist alfuzosin 10 mg once daily. Alfuzosin improves LUTS, peak urinary flow rates, and disease-specific quality of life, reduces the long-term risk of overall BPH progression, and is well tolerated in aging men, with minimal vasodilatory and sexual function side effects, even in those with comorbidities. Alfuzosin is well tolerated when used in combination with antihypertensive medications and phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction. The long-term clinical efficacy and good cardiovascular and sexual function safety profile of alfuzosin can contribute to an improved quality of life for aging men with LUTS/BPH.
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PMID:Medical therapy options for aging men with benign prostatic hyperplasia: focus on alfuzosin 10 mg once daily. 1898 21

Eisenmenger syndrome (ES), the most advanced form of pulmonary arterial hypertension (PAH) associated with congenital heart disease, is a devastating condition that has a considerable impact on patients' lives. Patients who develop ES typically exhibit 1 or more of a range of cardiac defects, including ventricular septal defects, atrial septal defects, and patent ductus arteriosus. The nature of the congenital defect underlying ES is important because it has prognostic implications. Although ES shares similar morphological findings with idiopathic PAH, clinical differences exist between the 2 etiologies. Adults with ES exhibit increased survival and more favorable hemodynamics than those with idiopathic PAH. Treatment options for patients with ES have historically been limited; however, recent successes have been achieved with the use of therapies targeted against the pathophysiological pathways that underlie PAH. The dual endothelin receptor antagonist bosentan was demonstrated to improve hemodynamics and exercise capacity without compromising oxygen saturation, both in the short and long term. Improvements in hemodynamics also have been observed with the single endothelin receptor antagonist sitaxsentan. The phosphodiesterase type V inhibitor sildenafil may improve functional class, oxygen saturation, and hemodynamics in patients with ES, and beneficial effects of prostacyclin and prostacyclin analogs in patients with ES have been reported. The treatment of patients with PAH with the use of combinations of targeted therapies is becoming increasingly commonplace and may offer an alternative option for treatment of patients with ES. The authors of future studies may seek to investigate whether the pulmonary vascular remodeling in ES can be targeted and reversed.
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PMID:Eisenmenger syndrome a clinical perspective in a new therapeutic era of pulmonary arterial hypertension. 1924 62

Major advances have been made in the understanding and treatment of pulmonary hypertension in the last few years. Without treatment (medication) for idiopathic pulmonary arterial hypertension, which is a rare and potentially fatal condition, the survival time is only about 3 years after diagnosis. However, if pulmonary hypertension is secondary to other causes such as congenital heart disease, it is possible to survive for 30 years or more without treatment. The condition can affect children at any age, from fetal life to adulthood. Patients with pulmonary hypertension can present to the respiratory pediatrician with unresponsive asthma, to the neurologist with faints, or to the general pediatrician with failure to thrive. Over the last few years there have been significant developments in the available therapy for managing this complicated disease. There is now a generally recognized ladder of long-term therapy for chronic pulmonary hypertension. Treatment can start with oxygen at home at night or even during the day. Next is the use of oral phosphodiesterase inhibitors, mostly type V, such as sildenafil, which enhance endogenous nitric oxide. More potent are the endothelin receptor antagonists and the most potent are the prostanoids, especially epoprostenol, which is given by constant intravenous infusion. In addition to interventional catheterization with atrial septostomy, these agents have improved the prognostic outlook. This article reviews the current knowledge about the etiology, investigation, and treatment of children with pulmonary hypertension in the clinical setting.
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PMID:Etiology, diagnosis, and pharmacologic treatment of pediatric pulmonary hypertension. 1930 33

In the pediatric population, pulmonary hypertension may present as an acute event in the setting of lung or cardiac pathology or as a chronic disease, mainly as idiopathic pulmonary hypertension or associated with congenital heart disease. Recently, new pharmacologic approaches have demonstrated significant efficacy in the management of adults with pulmonary arterial hypertension; these include intravenous epoprostenol, prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. The same treatment strategies are currently used in children. There are only few reports of the use of inhaled iloprost in pediatrics, only one of which reported the use of chronic inhaled iloprost in a significant number of children. This report showed that 1) the acute pulmonary vasodilator response to inhaled iloprost is equivalent to that of inhaled nitric oxide; 2) acute inhalation of iloprost can induce bronchoconstriction 3) the addition of inhaled iloprost can reduce the need for intravenous prostanoid therapy in some patients; 4) most children tolerated the combination of inhaled iloprost and endothelin receptor antagonist or phosphodiesterase inhibitors; 5) Several patients had clinical deterioration during chronic inhaled iloprost therapy and required rescue therapy with intravenous prostanoids. In this review we will discuss the role of inhaled iloprost in acute and chronic pulmonary hypertension in children.
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PMID:Review of inhaled iloprost for the control of pulmonary artery hypertension in children. 1943 72

Congenital heart disease can predispose individuals to pulmonary vascular remodeling as a result of the abnormality in pulmonary blood flow and pressure that accompanies the specific congenital defect being considered. Pulmonary arterial hypertension associated with congenital heart defects is an important determinant of functional capacity and survival, especially when the Eisenmenger's state of reversed shunt is present. The likelihood of right ventricular dysfunction and failure increases with the degree of pulmonary artery pressure. Thus, the aim of disease management in this patient population should be to prevent or improve right heart failure. Current therapies that modify the progression of pulmonary vascular disease-including endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids-should be considered carefully in patients with congenital heart disease-associated pulmonary hypertension. The risks and benefits of altering the balance of pulmonary vascular resistance to systemic vascular resistance must be weighed for each patient.
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PMID:Pulmonary hypertension complicating congenital heart disease. 1956 32

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This review summarizes the available data describing the use, safety, and efficacy of sildenafil for children with pulmonary hypertension.
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PMID:Sildenafil for the treatment of pulmonary hypertension in pediatric patients. 1970 81

Pulmonary hypertension (PH) is a relatively common hemodynamic finding in patients with left-sided heart disease and is usually associated with increased morbidity and mortality. However, so far no study has demonstrated long-term benefit from drugs specifically designed to improve pulmonary hemodynamics. There are currently no consensus recommendations on the management of PH in patients with chronic left heart failure. Most importantly, the underlying cause of left heart disease should be treated first. While previous studies with endothelin receptor antagonists or epoprostenol have been disappointing, initial promising results have been published for the phosphodiesterase-5 inhibitor sildenafil. Following acute administration and with chronic therapy for up to 6 months sildenafil improved hemodynamic parameters and exercise capacity in patients with PH and chronic left heart failure. Until the results from larger randomized controlled trials become available, the treatment of chronic left heart failure should follow the current guidelines.
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PMID:[Pulmonary hypertension in left heart disease]. 1971 7


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