Cardiac remodelling in the highest city in the world: effects of altitude and chronic mountain sickness.

AIMS: A unique Andean population lives in the highest city of the world (La Rinconada, 5100 m, Peru) and frequently develops a maladaptive syndrome, termed chronic mountain sickness (CMS). Both extreme altitude and CMS are a challenge for the cardiovascular system. This study aims to evaluate cardiac remodelling and pulmonary circulation at rest and during exercise in healthy and CMS highlanders. METHODS AND RESULTS: Highlanders living permanently at 3800 m (n = 23) and 5100 m (n = 55) with (n = 38) or without CMS (n = 17) were compared with 18 healthy lowlanders. Rest and exercise echocardiography were performed to describe cardiac remodelling, pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR). Total blood volume (BV) and haemoglobin mass were determined in all people. With the increase in the altitude of residency, the right heart dilated with an impairment in right ventricle systolic function, while the left heart exhibited a progressive concentric remodelling with Grade I diastolic dysfunction but without systolic dysfunction. Those modifications were greater in moderate-severe CMS patients. The mean PAP was higher both at rest and during exercise in healthy highlanders at 5100 m. The moderate-severe CMS subjects had a higher PVR at rest and a larger increase in PAP during exercise. The right heart remodelling was correlated with PAP, total BV, and SpO2. CONCLUSION: Healthy dwellers at 5100 m exhibit both right heart dilatation and left ventricle concentric remodelling with diastolic dysfunction. Those modifications are even more pronounced in moderate-severe CMS subjects and could represent the limit of the heart's adaptability before progression to heart failure.

Obstructive sleep apnea and cardiovascular disease

Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk, mediated through pathophysiological mechanisms that include intermittent hypoxia, excessive sympathetic nervous activation and exaggerated swings in negative intrathoracic pressure (2, 3). While it has previously been established from randomized controlled trials (RCT) that treatment of OSA with continuous positive airway pressure (CPAP) reduces blood pressure, with the most marked effects seen in drug-resistant hypertension (4), data to support a role for CPAP therapy to reduce cardiovascular mortality comes largely from observational studies (5, 6). To address this, McEvoy et al. conducted a multicentre, randomized, parallel-group trial to evaluate the efficacy of CPAP in reducing cardiovascular mortality in patients with moderate-to-severe OSA (oxygen desaturation index ≥ 12) and a history of coronary artery disease or cerebrovascular disease , who were mildlyor non-sleepy (Epworth Sleepiness Scale less or equal to 15) (1). Patients were excluded if they had severe hypoxia (oxygen saturation <80%) or if they had a Cheyne-Stokes respiration pattern. The primary endpoint included a composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for unstable angina, heart failure or transient ischemic attack. 2687 subjects were randomized to either "usual care" (n=1341) or "usual care" plus CPAP (n=1346). After a mean follow up of 3.7 years, there was no significant difference in the occurrence of the primary endpoint between the groups (hazard ratio (HR) with CPAP added, 1.10; 95% confidence interval (CI) 0.91 to 1.32; p = 0.34). Mean duration of adherence to CPAP therapy was 3.3 hours per night. A one-to-one propensity score analysis performed to compare 561 adherent patients (CPAP used for more than 4h/night) and 561 patients in the usual care group, showed no significant difference in the primary endpoint (HR 0.80; 95% CI : 0.60-1.07; p = 0.13), but a lower risk of cerebrovascular events among the CPAP group (HR 0.52; 95% CI : 0.30-0.90; p = 0.02). The results of this relatively large RCT are clearly an important addition to the current knowledge base and certainly, on the basis of this one study, CPAP cannot be recommended as a therapy in moderate to severe OSA patients with established cardiovascular disease if the sole purpose is to reduce cardiovascular complications. This trial affirms the results of other studies in highlighting the uncertain efficacy of CPAP therapy in the reduction of cardiovascular risk in non-symptomatic OSA patients over the short to medium term, and also highlights the challenge of CPAP adherence (7, 8). However, it is important that these results are not extrapolated to those OSA patients who do have excessive daytime sleepiness or significant hypoxia given these patients were excluded from the study. (AU)