Arterial Hypertension and Stroke Prevention: An Update

High blood pressure (BP) is the most important modifiable risk factor for stroke and other vascular diseases. Evidence from randomized controlled trials supports the use of antihypertensive drugs to lower blood pressure for stroke prevention. There is some evidence that specific classes of antihypertensive drugs have different effects and/or their pharmacological actions differ in patient subgroups. This review evaluates the development of antihypertensive therapies and the latest studies of arterial hypertension and stroke prevention: HOPE trial (ramipril versus placebo), ALLHAT trial (CCB or/and Angiotensin-Conventing enzyme Inhibitors (ACE-Is) versus diuretic), LIFE trial (losartan versus atenolol), and PROGRESS trial (perindopril or/and indapamide versus placebo). Despite the results of these relevant clinical trails, some aspects still remain unresolved. Future clinical trials on hypertension and stroke prevention should answer the following questions: Does lowering BP reduce stroke risk due to specific drug effect or class effect? Are angiotensin II receptor blockers (ARBs) better than ACE-Is? Should ACE-Is and ARBs be considered routinely for either high-risk stroke patients or patients with history of stroke or transient ischemic attack, irrespective of blood pressure? What is the role of lifestyle in BP control?     

Pulmonary Arterial Hypertension

The treatment of pediatric pulmonary arterial hypertension (PAH) is challenging due to the serious nature of the disease, its rapid progression, and the limited treatment options available. While oral calcium channel antagonists and continuous intravenous epoprostenol have been used successfully for over a decade, novel treatment options - including prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors - may change the course of this disease for many children in the future.Prostacyclin analogs offer the benefit over continuous intravenous epoprostenol of an alternative delivery system. However, the efficacy of these medications compared with intravenous epoprostenol and the risk/benefits of each analog need to be weighed in future trials, which need to include larger numbers of pediatric patients to optimize therapy and outcome for individual children with PAH.For patients who do not have an acute response to vasodilator testing or have failed treatment with oral calcium channel antagonists, endothelin receptor antagonists may offer a viable treatment option. Furthermore, in the future, the addition of endothelin receptor antagonists to long-term therapy with calcium channel antagonists or to epoprostenol or a prostacyclin analog may increase the overall efficacy of treatment of PAH. Large multi-institutional randomized trials to determine whether sildenafil is effective and safe for the long-term treatment of PAH in children are in progress.A comprehensive review of these newer agents with an emphasis on the pathobiology/pathophysiology of PAH provides insight into the future management of pediatric PAH patients.     

Update on Clinical Guidelines for Treatment of Hypertension

The potential benefit of fish oil (omega-3 fatty acids) consumption to reduce cardiovascular disease (CVD) risk remains controversial. Some investigations report reduced CVD risk associated with fish or fish oil consumption while others report no benefit. This controversy is in part resolved when consideration is given to omega-3 blood levels in relation to CVD risk as well as blood levels achieved in clinical trials of omega-3 supplementation and CVD benefit. There is a wide variation in omega-3 blood levels achieved between individuals in response to a given dose of an omega-3 supplement. Many studies tested a daily dose of 1 gram omega-3 supplementation. The individual variation in blood omega-3 levels achieved in response to a fixed daily dose helps to explain why some individuals may obtain CVD protection benefit while others do not due to failure to achieve a therapeutic threshold. Recent development of a population range in a United States population helps to provide clinical guidance since population omega-3 blood level ranges may vary due to environmental and genetic reasons. Omega-3 supplementation may also be of benefit in reducing the adverse impact of air pollution on CVD risk.     

An Update on Medical Therapy for Pulmonary Arterial Hypertension

Over the past 20 years, great progress has been made in the treatment of pulmonary arterial hypertension (PAH). Available therapies target one of three principal pathways: the endothelin (ET), nitric oxide (NO) or the prostacyclin (PGI2) pathway. Evidence shows that current drugs, used either as monotherapy or in different combinations, can improve exercise capacity, clinical symptoms, hemodynamics and even survival in PAH. Unfortunately, the disease remains incurable and the prognosis of the disease is still poor. However, existing and novel potent antiproliferative therapies are being explored, and new agents targeting different and/or additional pathways are likely to become available to clinicians in the near future. Promising candidates include tyrosine kinase antagonists (e.g. imatinib); soluble guanylate cyclase stimulators (riociguat); an oral analog of prostacyclin (selexipag); and a tissue targeting endothelin receptor antagonist (macitentan). Phase II or III trials have either been completed or are underway to evaluate the safety and efficacy of these various therapies.     

Pediatric Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) can cause morbidity and mortality in children. Although adult and pediatric PAH share many similarities, many differences have been found in children. Thus, a new classification for pediatric pulmonary hypertensive vascular disease has been proposed. Both child and adult gene mutation carriers with PAH tend to have worse prognoses. Pediatric patients present with better preserved functional class, and parents should pay high attention to any children with unexplained shortness of breath, fatigue or syncope, as symptoms of PAH in children are often misleading. Right heart catheterization is necessary for diagnosis. Although there are few medications approved for pediatric PAH and evidence-based treatment algorithms for children are still lacking, the survival of pediatric patients has been improved significantly since targeted therapies approved for adults were introduced to pediatric patients. PAH in children is unique, and further studies are needed to have a better understanding of it.     

Dasatinib-Induced Pulmonary Arterial Hypertension

A 73-year-old woman with chronic myeloid leukemia developed severe pulmonary arterial hypertension (PAH) and pleural effusions after treatment with dasatinib. During workup, partial anomalous pulmonary venous connection and a sinus venosus atrial septal defect were found; these anomalies may have predisposed her to developing this rare and life-threatening condition. Fortunately, her PAH was completely reversible by discontinuation of dasatinib. This case highlights dasatinib’s ability to cause PAH in patients predisposed to pulmonary vascular disease.