David A. Calhoun, MD, Professor of Medicine
Dr. David Calhoun is a Professor of Medicine in the Division of Cardiovascular Diseases at the University of Alabama at Birmingham (UAB). Dr. Calhoun is also a faculty member of the UAB Sleep/Wake Disorders Center. Dr. Calhoun received his undergraduate and medical degrees from the University of Virginia, Charlottesville, Virginia and then completed his internal medicine residency training at UAB. After residency, he did a post-doctoral research fellowship with Dr. Suzanne Oparil. As current Medical Director of the Vascular Biology and Hypertension Program, Dr. Calhoun oversees all clinical research within the Hypertension Program. Dr. Calhoun's laboratory has been focused on identifying mechanisms of treatment resistant hypertension. Important findings from this line of work have included identification of hyperaldosteronism as an important cause of antihypertensive treatment failure, benefit of mineralocorticoid receptor antagonists for resistant hypertension, and aldosterone excess as an important mediator of the severity of obstructive sleep apnea.
Resistant hypertension is defined as high blood pressure that requires 3 or more antihypertensive agents for treatment. Epidemiologic studies indicate that resistant hypertension is a common clinical problem, with an estimated prevalence of 15-20% of all adults being treated for hypertension. Important risk factors for developing resistant hypertension include older age, obesity, chronic kidney disease, African American race, and diabetes. We have reported that hyperaldosteronism is common in patients with resistant hypertension, affecting at least 20% of patients with resistant hypertension. While it has been recognized that the risk of having obstructive sleep apnea (OSA) is in increased in patients with resistant hypertension, the etiology of this association has not been fully explained. In evaluating patients with resistant hypertension and OSA by biochemical assessment and polysomnography, we reported a strong correlation between severity of OSA and aldosterone levels. We hypothesized that aldosterone excess, by inducing sodium and fluid retention, was contributing to upper airway edema and consequential increases in airway resistance. To further test for a possible mechanistic role between OSA and fluid retention, we assessed the relation between OSA severity and dietary salt intake. Relying on full, overnight sleep studies to quantify severity of OSA and 24-hour urine excretion to assess dietary sodium intake, we observed a positive correlation between increasing OSA severity and increasing sodium intake, particularly in patients with higher aldosterone levels. These findings implicate dietary salt excess as an important mediator of OSA in patients with resistant hypertension. If true, dietary salt restriction and/or use of aldosterone antagonists may serve as an important adjunct for treatment of OSA in patients prone to salt sensitivity.
Our laboratory has been exploring mechanisms of antihypertensive treatment resistant and antihypertensive treatment failure. Important findings have included identification of even mild hyperaldosteronism as an important cause of antihypertensive treatment resistance. Recent studies suggest that this aldosterone excess is related to weight gain, particularly increases in central adiposity. These observations have lead us to hypothesize that abdominal adipocytes may serve as a source of aldosterone secretagogues, leading to excess aldosterone independent of the classical renin-angiotensin-aldosterone pathway. Having identified aldosterone excess as a common cause of resistant hypertension, subsequent translational studies from our laboratory demonstrated mineralocorticoid receptor antagonists and dietary salt restriction as important therapeutic interventions for hypertension in this setting. More recently, our laboratory has proposed an extreme phenotype of antihypertensive failure that we are referring to as "refractory hypertension". Early assessments of this small but high-risk group of patients suggests that their extreme resistance to treatment may be related to heightened sympathetic output, as evidenced by higher heart rates and increased vascular resistance. Studies currently ongoing in our laboratory are testing this possibility.
Dr. Calhoun has prior and ongoing leadership positions in the American Society of Hypertension and the American Heart Association High Blood Pressure Research Council. He serves as editor of the Journal of Human Hypertension and regular Guest Editor of the journal Hypertension. Dr. Calhoun served as chairman for the first American Heart Association Scientific Statement on the Evaluation and Treatment of Resistant Hypertension, published in 2008.