Hassam Saif

CPAP, Weight Loss, or Both for Obstructive Sleep Apnea

BACKGROUND Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear. METHODS We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure. RESULTS Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone. CONCLUSIONS In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .).

Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.

Normative values and correlates of carotid artery intima-media thickness and carotid atherosclerosis in Andean-Hispanics: The Prevencion Study

OBJECTIVES Carotid intima-media thickness (cIMT) is an independent predictor of cardiovascular risk. Furthermore, ethnicity and gender-specific normative data are required to assess cIMT, which are not available for Andean-Hispanics. In addition, data regarding correlates of subclinical atherosclerosis in ethnic population are needed. METHODS We studied 1448 adults enrolled in a population-based study in Peru. cIMT and carotid plaque were measured with high-resolution ultrasonography. A healthy reference sample (n=472) with no cardiovascular disease, normal weight and normal metabolic parameters was selected to establish normative cIMT values. Correlates of abnormal cIMT and carotid plaque were assessed in the entire population. RESULTS In the reference sample, 95th-percentile cIMT values were both age and gender-dependent. In stepwise regression, selected predictors of increasing cIMT were: older age, impaired fasting glucose, diabetes mellitus, higher systolic blood pressure, higher LDL-cholesterol, smoking and male gender. Predictors of carotid plaque included older age, male gender, higher systolic blood pressure, lower diastolic blood pressure and higher LDL-cholesterol. HDL-cholesterol and C-reactive protein were not associated with cIMT or carotid plaque. The lack of association with HDL-cholesterol was confirmed using high performance liquid chromatography. CONCLUSIONS We present ethnic-specific cut-offs for abnormal cIMT applicable to Andean-Hispanics and correlates of subclinical atherosclerosis in this population. Pending longitudinal studies, our data supports several risk associations seen in other populations and can be used to identify Andean-Hispanics at increased risk for atherosclerotic cardiovascular disease. The lack of association between HDL-C and cIMT or carotid plaque in this population requires further investigation.

Effect of Continuous Positive Airway Pressure, Weight Loss, or Continuous Positive Airway Pressure Plus Weight Loss on Central Hemodynamics and Arterial Stiffness

Obesity and obstructive sleep apnea tend to coexist. Little is known about the effects of obstructive sleep apnea, obesity, or their treatment on central aortic pressures and large artery stiffness. We randomized 139 adults with obesity (body mass index >30 kg/m2) and moderate-to-severe obstructive sleep apnea to (1) continuous positive airway pressure (CPAP) therapy (n=45), (2) weight loss (WL) therapy (n=48), or (3) combined CPAP and WL (n=46) for 24 weeks. We assessed the effect of these interventions on central pressures and carotid–femoral pulse wave velocity (a measure of large artery stiffness), measured with arterial tonometry. Central systolic pressure was reduced significantly only in the combination arm (−7.4 mm Hg; 95% confidence interval, −12.5 to −2.4 mm Hg; P=0.004), without significant reductions detected in either the WL-only (−2.3 mm Hg; 95% confidence interval, −7.5 to 3.0; P=0.39) or the CPAP-only (−3.1 mm Hg; 95% confidence interval, −8.3 to 2.0; P=0.23) arms. However, none of these interventions significantly changed central pulse pressure, pulse pressure amplification, or the central augmentation index. The change in mean arterial pressure (P=0.008) and heart rate (P=0.027) induced by the interventions was significant predictors of the change in carotid–femoral pulse wave velocity. However, after adjustment for mean arterial pressure and heart rate, no significant changes in carotid–femoral pulse wave velocity were observed in any group. In obese subjects with obstructive sleep apnea, combination therapy with WL and CPAP is effective in reducing central systolic pressure. However, this effect is largely mediated by changes in mean, rather than central pulse pressure. WL and CPAP, alone or in combination, did not reduce large artery stiffness in this population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00371293.Obesity and obstructive sleep apnea tend to coexist. Little is known about the effects of obstructive sleep apnea, obesity, or their treatment on central aortic pressures and large artery stiffness. We randomized 139 adults with obesity (body mass index >30 kg/m 2 ) and moderate-to-severe obstructive sleep apnea to (1) continuous positive airway pressure (CPAP) therapy (n=45), (2) weight loss (WL) therapy (n=48), or (3) combined CPAP and WL (n=46) for 24 weeks. We assessed the effect of these interventions on central pressures and carotid–femoral pulse wave velocity (a measure of large artery stiffness), measured with arterial tonometry. Central systolic pressure was reduced significantly only in the combination arm (−7.4 mm Hg; 95% confidence interval, −12.5 to −2.4 mm Hg; P =0.004), without significant reductions detected in either the WL-only (−2.3 mm Hg; 95% confidence interval, −7.5 to 3.0; P =0.39) or the CPAP-only (−3.1 mm Hg; 95% confidence interval, −8.3 to 2.0; P =0.23) arms. However, none of these interventions significantly changed central pulse pressure, pulse pressure amplification, or the central augmentation index. The change in mean arterial pressure ( P =0.008) and heart rate ( P =0.027) induced by the interventions was significant predictors of the change in carotid–femoral pulse wave velocity. However, after adjustment for mean arterial pressure and heart rate, no significant changes in carotid–femoral pulse wave velocity were observed in any group. In obese subjects with obstructive sleep apnea, combination therapy with WL and CPAP is effective in reducing central systolic pressure. However, this effect is largely mediated by changes in mean, rather than central pulse pressure. WL and CPAP, alone or in combination, did not reduce large artery stiffness in this population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00371293.

EFFECT OF CONTINUOUS-POSITIVE AIRWAY PRESSURE, WEIGHT LOSS OR BOTH ON LARGE ARTERY STIFFNESS IN SUBJECTS WITH OBSTRUCTS SLEEP APNEA

Obesity and obstructive sleep apnea (OSA) have been associated with increased large artery stiffness. We assessed the effects of weight loss, continuous positive airway pressure (CPAP) therapy, or their combination on carotid-femoral pulse wave velocity (cf-PWV), the gold-standard index of large

TIME-RESOLVED LEFT VENTRICULAR MYOCARDIAL STRESS IN HEART FAILURE WITH REDUCED EJECTION FRACTION REVEALS A MARKED INCREASE IN LATE SYSTOLIC MYOCARDIAL LOAD

Systolic myocardial wall stress (MWS) quantifies myocardial afterload. Despite its time-varying nature, little data exist regarding time-resolved MWS in systolic heart failure (HF). We studied 10 subjects with systolic HF (mean LV ejection fraction=40%). We assessed time-resolved LV volume and