Lama Ghazi

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Prospective studies indicate that hyperaldosteronism is found in 20% of patients with resistant hypertension. A small number of observational studies in normotensive and hypertensive patients suggest a correlation between aldosterone levels and obesity while others could not confirm these findings. The correlation between aldosterone levels and body mass index (BMI) in patients with resistant hypertension has not been previously investigated. Our objective was to determine whether BMI is positively correlated with plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, and 24-hour urinary aldosterone in black and white patients. We performed a cross-sectional analysis of a large diverse cohort (n=2170) with resistant hypertension. The relationship between plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, 24-hour urinary aldosterone, and BMI was investigated for the entire cohort, by sex and race (65.3% white, 40.3% men). We demonstrate that plasma aldosterone concentration and aldosterone:renin ratio were significantly correlated to BMI (P<0.0001) across the first 3 quartiles, but not from the 3rd to 4th quartile of BMI. Plasma renin activity was not correlated with BMI. Twenty-four–hour urinary aldosterone was positively correlated across all quartiles of BMI for the cohort (P<0.0001) and when analyzed by sex (men P<0.0001; women P=0.0013) and race (P<0.05), and stronger for men compared with women (r=0.19, P<0.001 versus r=0.05, P=0.431, P=0.028) regardless of race. In both black and white patients, aldosterone levels were positively correlated to increasing BMI, with the correlation being more pronounced in black and white men. These findings suggest that obesity, particularly the abdominal obesity typical of men, contributes to excess aldosterone in patients with resistant hypertension.

Urinary sodium excretion predicts blood pressure response to spironolactone in patients with resistant hypertension independent of aldosterone status.

Objective: Resistant hypertension (RHTN), blood pressure (BP) at least 140/90 mmHg despite using at least three different medications, including a diuretic, is associated with high dietary sodium and hyperaldosteronism. Mineralocorticoid receptor antagonists are recommended for treatment of RHTN, however, BP response to these agents varies widely. In the current analysis, we assessed predictors of BP response to spironolactone in patients with RHTN. Methods: We retrospectively evaluated the BP response to adding spironolactone 12.5–25 mg to existing medications. A favorable BP response was defined as a reduction in SBP of at least 10 mmHg. Tested variables included baseline characteristics and biochemical parameters. Results: A total of 79 patients with RHTN were included in the analysis. Evaluated patients were more likely women (53.2%) and African-American (55.8%); were generally obese (76%) and were prescribed an average of four antihypertensive medications. Baseline SBP was 153.6 ± 22.3 mmHg; addition of spironolactone resulted in a mean reduction of 15.5 ± 20.7 mmHg. Patients with high urinary sodium excretion (≥200 mEq/24 h) had a significantly greater BP reduction compared with patients with normal excretion (<200 mEq/24 h) (P = 0.008). Multivariable analysis identified 24 h urinary sodium excretion as a significant predictor of BP response (P = 0.021) after controlling for potential confounders, including primary aldosteronism. Conclusion: The antihypertensive effect of spironolactone is positively related to urinary sodium excretion regardless of aldosterone status. These findings suggest that mineralocorticoid receptor antagonists may be of preferential benefit in counteracting the BP effects of high dietary sodium.

Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ⩽40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ⩽40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P<0.0001), higher rates of obesity (53.4% versus 26.9%; P<0.0001), and significantly higher levels of plasma aldosterone (11.3±9.8 versus 8.9±7.4 ng/dL; P=0.005), plasma renin activity (4.9±10.2 versus 2.5±5.0 ng/mL per hour; P=0.001), 24-hour urinary aldosterone (13.4±10.0 versus 8.2±6.2 µg/24 h; P<0.0001), and sodium excretion (195.9±92.0 versus 146.8±67.1 mEq/24 h; P<0.0001). Among patients with resistant hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly.

Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension

Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ⩽40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ⩽40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P<0.0001), higher rates of obesity (53.4% versus 26.9%; P<0.0001), and significantly higher levels of plasma aldosterone (11.3±9.8 versus 8.9±7.4 ng/dL; P=0.005), plasma renin activity (4.9±10.2 versus 2.5±5.0 ng/mL per hour; P=0.001), 24-hour urinary aldosterone (13.4±10.0 versus 8.2±6.2 µg/24 h; P<0.0001), and sodium excretion (195.9±92.0 versus 146.8±67.1 mEq/24 h; P<0.0001). Among patients with resistant hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly.

Race, Sex, Age, and Regional Differences in the Association of Obstructive Sleep Apnea With Atrial Fibrillation: Reasons for Geographic and Racial Differences in Stroke Study

STUDY OBJECTIVES To examine the cross-sectional association between obstructive sleep apnea (OSA) risk and atrial fibrillation (AF) in the REasons for Geographic And Racial Differences in Stroke (REGARDS), a cohort of black and white adults. METHODS Using REGARDS data from subjects recruited between 2003-2007, we assessed 20,351 participants for OSA status. High OSA risk was determined if the participant met at least two criteria from the Berlin Sleep Questionnaire (persistent snoring, frequent sleepiness, high blood pressure, or obesity). AF was defined as a self-reported history of a previous physician diagnosis or presence of AF on electrocardiogram. Logistic regression was used to determine odds ratio and 95% confidence interval for the association between OSA status and AF with subgroup analysis to examine effect modification by age, race, sex, and geographical region. RESULTS The prevalence of AF was 7% (n = 1,079/14,992) and 9% (n = 482/5,359) in participants at low and high risk of OSA, respectively (P < .0001). Persons at high risk of OSA had greater prevalence of diabetes and stroke history, and were more likely to be obese and taking sleep medications. In a multivariable analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, high risk for OSA was associated with an increased odds of AF compared to low risk for OSA (odds ratio = 1.27, 95% confidence interval = 1.13, 1.44). This association differed significantly only by race (P for interaction = .0003). For blacks, there was a significant 58% increase in odds of AF in participants at high risk versus low risk of OSA, compared to a nonsignificant 12% increase in odds in whites. We were limited by self-reported variables, inability to adjust for obesity, and the cross-sectional nature of our study. CONCLUSIONS High risk of OSA is associated with prevalent AF among blacks but not whites. COMMENTARY A commentary on this article appears in this issue on page 1459.

Distinctive Risk Factors and Phenotype of Younger Patients With Resistant HypertensionNovelty and Significance: Age Is Relevant

Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ⩽40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ⩽40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P<0.0001), higher rates of obesity (53.4% versus 26.9%; P<0.0001), and significantly higher levels of plasma aldosterone (11.3±9.8 versus 8.9±7.4 ng/dL; P=0.005), plasma renin activity (4.9±10.2 versus 2.5±5.0 ng/mL per hour; P=0.001), 24-hour urinary aldosterone (13.4±10.0 versus 8.2±6.2 µg/24 h; P<0.0001), and sodium excretion (195.9±92.0 versus 146.8±67.1 mEq/24 h; P<0.0001). Among patients with resistant hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly.

OS 24-04 A PILOT STUDY ASSESSING THE FEASIBILITY OF VASCULAR FUNCTION IN LOW SOCIOECONOMIC STATUS PRESCHOOL CHILDREN.

Objective: To assess the feasibility of measuring non-invasively central aortic blood pressure (BP) and indices of arterial stiffness (aortic augmentation index (AIx) and pulse wave velocity (PWV)) in 3–5 year old children and assess if vascular function is affected by vascular inflammation (Serum C-reactive protein (CRP)) and /or cortisol. Design and Method: Central BP, AIx, and PWV were measured using applanation tonometry (SphygmoCor) in 16 children recruited from Head Start centers in AL. Results: We recruited 16 preschool African American children (age 53.1 ± 9.1 months, 69% males, weight 39.8 ± 8 lbs, height 36.2 ± 3.2 in). Of these 38% (n = 6) had an elevated blood pressure reading (> 90% for height, gender and age). BMI were comparable between the groups. Brachial (111 ± 9/69 ± 4 vs. 93 ± 11/55 ± 6 mmHg, p < 0.05) and central (93 ± 12/72 ± 6 vs. 85 ± 7/57 ± 6 mmHg, p < 0.05) BP, CRP (3.1[2.3–6.3] vs. 0.2[0.1–0.3] mg/L, p < 0.05) and cortisol (0.21 ± 0.09 vs. 0.15 ± 0.06, p = 0.09) were higher in children with hypertensive BP readings. There was no significant difference in PWV between the groups but AIx was higher in children with hypertensive BP readings (31 ± 8 vs.18 ± 16%, p = 0.07). Serum CRP correlated with systolic (Spearman r = 0.70) and diastolic (0.68) BP percentiles and with central systolic (0.58) and diastolic (0.71) BP readings (all p < 0.05) but not with AIx (0.25, p = 0.4) or PWV (−0.2, p > 0.9). Serum cortisol showed moderate correlations with AIx (0.43, p = 0.1) and PWV (-0.48, p = 0.1) but not with BP readings. Conclusions: Non-invasive assessment of central aortic BP and measures of arterial stiffness are feasible in preschool children. Children with hypertensive BP readings may have evidence of arterial stiffness as early as 3–5 years of age. Vascular function is associated with inflammatory and stress markers. Further studies are needed to determine vascular function changes in preschool children to elucidate mechanisms of early onset hypertension.

PS 14-14 24-HOUR URINARY SODIUM PREDICTS LEFT VENTRICULAR HYPERTROPHY REGRESSION TO SPIRONOLACTONE IN PATIENTS WITH RESISTANT HYPERTENSION

Objective: Patients with resistant hypertension (RHTN) commonly have primary aldosteronism (PA), which is associated with left ventricular hypertrophy (LVH). Aldosterone activates mineralocorticoid receptors (MR) and induces hypertrophy. Experimental studies indicate a paradoxical activation of the MR in sodium-loaded rats despite adequate suppression of aldosterone. MR antagonists slow down cardiac hypertrophy. We hypothesized that the MR antagonist spironolactone (SPL) would cause greater LVH reduction in patients on high sodium (Na) diet independent of aldosterone. Design and Method: Overall 34 patients with RHTN, defined as BP ≥ 140/90 mmHg despite ≥3 different medications, including a diuretic, were treated with SPL. Cardiac magnetic resonance imaging and biochemical evaluation was performed at baseline, 3 and 6 months in patients with PA and non-PA. PA was defined as renin activity (PRA) <1 ng/ml/h and urinary aldosterone ≥12 ug /24h. We dichotomized patients according to UNa level (UNa ≥200 mEq/24h: high Na diet) and PA status. LVH reduction was indexed by left ventricular mass (LVM) and interventricular septum thickness (IVS) regression. Results: LVM and IVS regression after treatment with SPL at 3 and 6 months was greater in patients with PA on a normal sodium diet and less pronounced in patients on a high sodium diet suggesting that Na blunts the effects of cardiac MR when treated with SPL. However, in patients with non-PA high Na intake did not blunt the effects of SPL. Conclusions: Contrary to our hypothesis, high dietary Na blunted LVH regression in patients with PA treated with SPL. Further studies are needed to elucidate mechanisms for sodium dependent MR activation in patients with PA and non-PA.

OS 33-02 IN PATIENTS WITH RESISTANT HYPERTENSION INCREASED 24-H URINARY CORTISOL LEVEL PREDICT INCREASED BODY MASS INDEX.

Objective: Obesity is associated with a high risk of hypertension and is characterized by hyperaldosteronism and hypercortisolism. We have previously reported that patients with resistant hypertension (RHTN), defined as blood pressure (BP) that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes, have a high prevalence of hyperaldosteronism that is positively correlated with body mass index (BMI). Experimental studies indicate that adipocytes secrete a as yet undetermined factor that stimulates aldosterone and cortisol release. Our objective was to determine in patients with RHTN if obesity as indexed by BMI is positively correlated with both 24-hour urinary aldosterone (24 h U-Aldo) and cortisol (24 h UCort) levels. Design and Method: Cross-sectional study of a cohort of 745 patients with RHTN referred to the Hypertension Clinic at the University of Alabama at Birmingham. All patients underwent 24 h U-Aldo and 24 h UCort evaluation. Results: Characteristics of the cohort were 50% females, 40% African Americans, BMI = 32.7 ± 6.9 kg/m2, systolic BP = 157.8 ± 25.6 mmHg, and diastolic BP = 87.6 ± 14.9 mmHg, and average number of medications 4.2 ± 1.2. 24 h UAldo (p = 0.0007) and 24-h UCort levels (p = 0.01) were both positively correlated across tertiles of BMI for the entire cohort. When analyzed by gender there was no difference in BMI but men had significantly higher UCort levels (161 ± 93 versus 120 ± 66 &mgr;g, p < 0.001) and the relation was stronger in men than women (r = 0.12 vs 0.08, p < 0.05) suggesting that visceral adipose tissue more characteristic of men is an important mediator. When analyzed by race there was no difference between Caucasian and African American subjects. Conclusions: Aldosterone and cortisol levels were positively related to BMI and higher in men than women suggesting that obesity, particularly visceral adiposity, contributes importantly to increases in both hormones possibly secondary to a common adipocyte-derived stimulus.