Veena Shetty

Hypoxia, Not the Frequency of Sleep Apnea, Induces Acute Hemodynamic Stress in Patients With Chronic Heart Failure

OBJECTIVES This study was conducted to evaluate whether brain (B-type) natriuretic peptide (BNP) changes during sleep are associated with the frequency and severity of apneic/hypopneic episodes, intermittent arousals, and hypoxia. BACKGROUND Sleep apnea is strongly associated with heart failure (HF) and could conceivably worsen HF through increased sympathetic activity, hemodynamic stress, hypoxemia, and oxidative stress. If apneic activity does cause acute stress in HF, it should increase BNP. METHODS Sixty-four HF patients with New York Heart Association functional class II and III HF and ejection fraction <40% underwent a baseline sleep study. Five patients with no sleep apnea and 12 with severe sleep apnea underwent repeat sleep studies, during which blood was collected every 20 min for the measurement of BNP. Patients with severe sleep apnea also underwent a third sleep study with frequent BNP measurements while they were administered oxygen. This provided 643 observations with which to relate apnea to BNP. The association of log BNP with each of 6 markers of apnea severity was evaluated with repeated measures regression models. RESULTS There was no relationship between BNP and the number of apneic/hypopneic episodes or the number of arousals. However, the burden of hypoxemia (the time spent with oxygen saturation <90%) significantly predicted BNP concentrations; each 10% increase in duration of hypoxemia increased BNP by 9.6% (95% confidence interval: 1.5% to 17.7%, p = 0.02). CONCLUSIONS Hypoxemia appears to be an important factor that underlies the impact of sleep abnormalities on hemodynamic stress in patients with HF. Prevention of hypoxia might be especially important for these patients.

Effect of Beta-Blocker Therapy on Rehospitalization Rates in Women Versus Men With Heart Failure and Preserved Ejection Fraction

Beta blockers are empirically used in many patients with heart failure (HF) and preserved ejection fraction (HFpEF) because they allow more time for diastolic filling and because they improve outcomes in patients with systolic HF. However, recent data suggest that impaired chronotropic and vasodilator responses to exercise, which can worsen with beta blockade, may play a key role in the pathophysiology of HFpEF. We prospectively examined the association between beta-blocker therapy after hospitalization for decompensated HF and HF rehospitalization at 6 months in 66 consecutive patients with HFpEF (71 +/- 13 years old, 68% women, 42% Black). Subjects were stratified based on receiving (BB+; 15 men, 28 women) or not receiving (BB-) beta-blockers at hospital discharge. In men, HF rehospitalization occurred less frequently in the BB+ than in the BB- group, albeit nonsignificantly (20% vs 50%, p = 0.29). In women, HF rehospitalization occurred more frequently in the BB+ than in the BB- group (75% vs 18%, p <0.001). In univariate analyses, discharge beta-blocker was associated with HF rehospitalization in women (odds ratio [OR] 14.00, 95% confidence interval [CI] 3.09 to 63.51, p = 0.001), but not in men (OR 0.25, 95% CI 0.03 to 1.92, p = 0.18). In a forward logistic regression model that offered all univariate predictors of HF rehospitalization, discharge beta blocker remained an independent predictor of HF rehospitalization in women (OR 11.06, 95% CI 1.98 to 61.67, p = 0.006). In conclusion, this small observational study suggests that beta-blocker therapy may be associated with a higher risk of HF rehospitalization in women with HFpEF. The risks and benefits of beta-blocker therapy in patients with HFpEF should be evaluated in randomized, controlled trials.

Is Longitudinal Pulse Pressure a Better Predictor of 24-Hour Urinary Albumin Excretion Than Other Indices of Blood Pressure?

The strong relationship between urinary albumin excretion (UAE) and pulse pressure (PP) in cross-sectional studies suggests that pressure pulsatility may contribute to renal microvascular injury. The longitudinal relationships between UAE and the various indices of blood pressure (BP) are not well studied. We compared the associations of UAE with the longitudinal exposure to PP and systolic, diastolic, and mean BPs. UAE was measured from 24-hour urine collections in 450 community-dwelling subjects (age: 57±15 years, 53% women, all with UAE <200 &mgr;g/min). For each subject, longitudinal indices of BP were estimated by dividing the area under the curve of serial measurements of BP (median: 5) during 1 to 22 years preceding UAE measurement by the number of follow-up years. Median (interquartile range) UAE was 4.7 &mgr;g/min (3.3 to 7.8 &mgr;g/min) in women and 5.2 &mgr;g/min (3.7 to 9.8 &mgr;g/min) in men. In women, UAE was not related to longitudinal indices of BP. In men, in multivariable-adjusted models that included either longitudinal systolic and diastolic BPs or longitudinal PP and mean BP, UAE was independently associated with systolic (standardized regression coefficient [&bgr;]=0.227; P=0.03) but not with diastolic (&bgr;=−0.049; P=0.59) BP and with PP (&bgr;=0.216; P=0.01) but not with mean BP (&bgr;=0.032; P=0.72). Comparisons of these 2 models and stepwise regression analyses both indicated that, of the 4 longitudinal indices of BP, PP was the strongest predictor of UAE in men. The pulsatile component of BP confers the highest risk for BP-induced renal microvascular injury. Future studies should examine whether PP reduction provides additional renoprotection beyond that attained by conventional BP goals alone.

Modeling a cross-sectional response variable with longitudinal predictors: an example of pulse pressure and pulse wave velocity

We wish to model pulse wave velocity (PWV) as a function of longitudinal measurements of pulse pressure (PP) at the same and prior visits at which the PWV is measured. A number of approaches are compared. First, we use the PP at the same visit as the PWV in a linear regression model. In addition, we use the average of all available PPs as the explanatory variable in a linear regression model. Next, a two-stage process is applied. The longitudinal PP is modeled using a linear mixed-effects model. This modeled PP is used in the regression model to describe PWV. An approach for using the longitudinal PP data is to obtain a measure of the cumulative burden, the area under the PP curve. This area under the curve is used as an explanatory variable to model PWV. Finally, a joint Bayesian model is constructed similar to the two-stage model.