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Background: Having previously reported that aldosterone levels increase progressively with body mass index (BMI), the current analysis was done to determine to what extent this association is related to dietary high salt intake. We anticipated that aldosterone levels would decrease with higher sodium status consistent with classical suppression of aldosterone release secondary to progressive fluid retention induced by high dietary sodium intake., Methods: Cross-sectional analysis of a large diverse cohort of 2,705 patients with resistant hypertension (HTN) seen in a referral HTN Clinic. Dietary sodium intake was indexed by 24-hour (h) urinary sodium (UNa), aldosterone status was determined by plasma aldosterone concentration, plasma renin activity, and 24 h urinary aldosterone (UAldo). Patients with normal weight served as control., Results: In this study, 1,572 individuals with complete 24 h urine collections were analyzed. Mean BMI was 32.5 ± 7.1 kg/m2 and ranged from 24.6 ± 2.4 kg/m2 (first quartile) to 41.0 ± 4.2 kg/m2 (fourth quartile). BMI was positively associated with 24 h UNa and UAldo levels (P < 0.0001), 24 h UNa and UAldo. There was a positively stronger correlation in obese (r = 0.273, P < 0.0001) compared with normal weight individuals (r = 0.108, P = 0.0342) independent of number and classes of antihypertensive medications., Conclusions: Our analysis shows that there is an altered regulation of aldosterone in obese patients in the setting of high dietary salt intake., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients., Methods: We prospectively measured systemic, renal vein (RV), inferior vena cava (IVC), and urinary copy number of the mtDNA genes COX3 and ND1 by quantitative-PCR in CEH and ObAAEH patients during constant sodium intake and antihypertensive regimens, and compared them with healthy volunteers (HV) (n = 23 each)., Results: Blood pressure was similarly elevated in CEH and ObAAEH, while glomerular filtration rate (GFR) was higher and age lower in ObAAEH. Urinary (but not plasma) COX3 and ND1 were higher in CEH compared to HV, and further elevated in ObAAEH patients. COX3 and ND1 renal gradients (RV-IVC) were higher in ObAAEH vs. CEH, and their urinary levels directly correlated with GFR. In multivariate analysis, GFR remained the only predictor of elevated urinary COX3 and ND1 levels., Conclusions: Urinary fragments of the mitochondrial genome are elevated in ObAAEH patients and correlate with glomerular hyperfiltration. A positive gradient across the kidney in ObAAEH suggests selective renal release. These results are consistent with mitochondrial injury that may aggravate renal damage and accelerate hypertension-related morbidity/mortality rates in ObAAEH., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

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., (© 2017 American Heart Association, Inc.)

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., (© 2016 American Heart Association, Inc.)

Background: Hypertension is the most prevalent and significant modifiable risk factor for coronary heart disease. A portion of patients with uncontrolled hypertension are considered to have resistant hypertension (RHTN). Myocardial ischemia incidence increases along with blood pressure (BP) levels. However, the prevalence of myocardial ischemia in patients with RHTN, as well as the factors associated with it, is unknown., Methods: We enrolled 129 patients with true RHTN regularly followed in our specialty hypertension clinic and evaluated then by resting and dipyridamole pharmacological stress myocardial perfusion scintigraphy. Patients were then divided into 2 groups: those with (I-RHTN; n = 36) and those without (NI-RHTN; n = 93) myocardial ischemia. Echocardiography, 24-hour ambulatory BP monitoring (ABPM), and flow mediated dilation (FMD) were also evaluated., Results: Thirty six (28%) patients had myocardial ischemia. There was no difference between groups regarding age, sex, biochemical parameters, office, and 24-hour ABPM levels. Patients in the I-RHTN group were more likely diabetic (31% vs. 11%; P < 0.05) and obese (75% vs. 40%; P < 0.001). Adjusting for age and body mass index, multiple logistic regression showed that diabetes (odds ratio (OR) = 6.5; 95% confidence interval (CI) = 1.06-40.14; P = 0.04), FMD (OR = 0.18; 95% CI = 0.07-0.41; P < 0.001), heart rate (OR = 1.23; 95% CI = 1.11-1.36; P < 0.001), left ventricular mass index (OR = 1.02; 95% CI = 1.01-1.04; P = 0.04), and microalbuminuria (OR = 1.02; 95% CI = 1.01-1.04; P = 0.002) were independent predictors of ischemia., Conclusions: In conclusion, there is a high prevalence of myocardial ischemia in patients with RHTN. Increased microalbuminuria, heart rate, endothelial dysfunction, and left ventricular mass can be useful to guide the investigation for myocardial ischemia in these high risk patients., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To evaluate the prevalence of and characterize resistant hypertension in a large representative population with successful hypertension management and reliable health information., Patient and Methods: We performed a cross-sectional study using clinical encounter, laboratory, and administrative information from the Kaiser Permanente Southern California health system between January 1, 2006, and December 31, 2007. From individuals older than 17 years with hypertension, resistant hypertension was identified and prevalence was determined. Multivariable logistic regression was used to calculate odds ratios (ORs), with adjustments for demographic characteristics, clinical variables, and medication use., Results: Of 470,386 hypertensive individuals, 60,327 (12.8%) were identified as having resistant disease, representing 15.3% of those taking medications. Overall, 37,061 patients (7.9%) had uncontrolled hypertension while taking 3 or more medicines. The ORs (95% CIs) for resistant hypertension were greater for black race (1.68 [1.62-1.75]), older age (1.11 [1.10-1.11] for every 5-year increase), male sex (1.06 [1.03-1.10]), and obesity (1.46 [1.42-1.51]). Medication adherence rates were higher in those with resistant hypertension (93% vs 89.8%; P<.001). Chronic kidney disease (OR, 1.84; 95% CI, 1.78-1.90), diabetes mellitus (OR, 1.58; 95% CI, 1.53-1.63), and cardiovascular disease (OR, 1.34; 95% CI, 1.30-1.39) were also associated with higher risk of resistant hypertension., Conclusion: In a more standardized hypertension treatment environment, we observed a rate of resistant hypertension comparable with that of previous studies using more fragmented data sources. Past observations have been limited due to nonrepresentative populations, reliability of the data, heterogeneity of the treatment environments, and less than ideal control rates. This cohort, which was established using an electronic medical record-based approach, has the potential to provide a better understanding of resistant hypertension and outcomes., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

A large body of evidence strongly links aldosterone to development and progression of cardiovascular disease, including vascular stiffness, left ventricular hypertrophy, congestive heart failure, chronic kidney disease, and, especially, hypertension. Emerging data suggest that adipocytes may serve as a source of aldosterone, either directly or indirectly, through the release of aldosterone-stimulating factors. If adipocytes are confirmed to have an important contribution to hyperaldosteronism, it would have significant clinical implications in linking aldosterone to obesity-related increases in cardiovascular risk. Such a cause-and-effect situation would then provide the opportunity to reverse that risk with preferential use of aldosterone antagonists in obese patients., (2010 Elsevier Ltd. All rights reserved.)

Obstructive sleep apnea, aldosterone excess, and resistant hypertension are common comorbidities in obese patients. The mechanisms that link these conditions are not fully elucidated, but sympathetic nervous system activation, sodium retention, renin-angiotensin-aldosterone system stimulation, endothelial dysfunction, and increased production of reactive oxidative species may be contributing factors. Patients diagnosed with this triad should be treated with low-salt diet, weight-loss counseling, and continuous positive airway pressure, as well as aggressive antihypertensive therapy, usually with multiple agents, including a mineralocorticoid receptor antagonist. Patients with aldosterone-producing adenoma may require adrenalectomy.

Hypertension resistant to 2 antihypertensive drugs is more common among obese patients than among lean patients. The case we describe and the observations we report suggest that refractoriness among obese hypertensives is frequently caused by obstructive sleep apnea and/or inappropriately high plasma aldosterone levels. In other words, obese hypertensives may have sleep apnea, obese hypertensives without sleep apnea may have inappropriately elevated levels of plasma aldosterone, and a surprising number of obese patients with sleep apnea also have elevated levels of aldosterone. The mechanisms by which obesity and obstructive sleep apnea increase aldosterone levels and raise blood pressure are not understood, but sympathetic nervous system activation and production of nonclassical adrenal stimuli are two possibilities. Obstructive sleep apnea can be detected with a careful history and various sleep studies. Inappropriately elevated aldosterone levels can be detected by measuring the ratio of plasma aldosterone concentration to plasma renin activity. Successful treatment of these resistant hypertensives often can be achieved by devices that provide positive pressure to the upper airway to correct obstructive sleep apnea and by incorporating an aldosterone antagonist in the therapeutic regimen.

BACKGROUND: Multiple studies indicate that primary aldosteronism (PA) is common in patients with resistant hypertension, with an estimated prevalence of approximately 20%. Additional studies suggest that beyond this 20% of patients with classical PA, there is a larger proportion of patients with lesser degrees of hyperaldosteronism which contributes even more broadly to antihypertensive treatment resistance. Given these observations, it is intuitive that use of aldosterone antagonists will provide antihypertensive benefit in patients with resistant hypertension and evidence of aldosterone excess. Intriguingly, however, are clinical findings demonstrating substantive benefit of aldosterone antagonists in patients with resistant hypertension, but without demonstrative evidence of hyperaldosteronism, that is, with seemingly normal or even low aldosterone levels. CONCLUSION: Spironolactone is clearly established as the most effective fourth agent for treatment of uncontrolled resistant hypertension. Emerging observations suggest a further role of spironolactone for counteracting the effects of diet high in sodium, particularly in obese, hypertensive patients. [ABSTRACT FROM AUTHOR]

Resistant hypertension affects an estimated 10-15 million American adults and is increasing in prevalence. The etiology of resistant hypertension is almost always multifactorial, including obesity, older age, high dietary salt, chronic kidney disease, and aldosterone excess. Classical primary aldosteronism and lesser degrees of aldosterone excess, possibly originating from visceral adipocytes, contribute broadly to antihypertensive treatment resistance. Treatment of resistant hypertension is predicated on appropriate lifestyle changes and use of effective combinations of antihypertensive agents from different classes. Blockade of aldosterone with spironolactone has been shown to be particularly effective for treatment of resistant hypertension. The antihypertensive benefit of spironolactone is not limited to patients with demonstrable hyperaldosteronism but instead can be effective in resistant hypertensive patients regardless of aldosterone levels. Chlorthalidone is a potent, long-acting thiazide-like diuretic and should be used preferentially to treat resistant hypertension as it is superior to normally used doses of hydrochlorothiazide. [ABSTRACT FROM AUTHOR]

BackgroundHigh waist circumference (WC) (women: >88 cm; men: >102 cm) increases cardiovascular risk. Less is known about moderate WC (women: 80-88 cm; men: 94-102 cm). Therefore, we examined the association between moderate WC and hypertension prevalence, independent of body mass index (BMI).MethodsAmong 24,247 eligible adults 45-84 years old, when recruited from January 2003 to October 2007 in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, we examined hypertension prevalence (systolic blood pressure (BP) ≥140 mm Hg, or diastolic BP ≥90 mm Hg, or self-reported antihypertensive medication use) by WC before and after stratification by BMI (normal: 18.5-24.9; overweight: 25-29.9; obese class I: 30-34.9). Logistic regression adjusted associations between WC, BMI, and hypertension prevalence for age, race, sex, region, income, education, cigarette smoking, glomerular filtration rate, alcohol use, and physical activity.ResultsOverall, hypertension prevalence was 44% among those with low WC (n = 8,068), 55% with moderate WC (n = 6,488), and 66% with high WC (n = 9,691). After full adjustment, moderate WC was independently associated with hypertension prevalence among persons with normal BMI, (adjusted odds ratio (aOR), 1.49; 95% confidence interval (CI), 1.31-1.70), overweight BMI (aOR, 1.80; 95% CI, 1.64-1.98), and obese class I BMI (aOR, 2.28; 95%CI, 1.96-2.65) (referent: low WC-normal BMI). The moderate WC-hypertension association was observed in blacks and whites and in men and women.ConclusionModerate WC is associated with hypertension prevalence independent of BMI and several hypertension risk factors in middle-aged and older adults.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.258 [ABSTRACT FROM AUTHOR]

Patients with resistant hypertension are those who have uncontrolled blood pressure despite use of three or more antihypertensive medications, or those who require four or more medications to achieve control. When evaluating resistant hypertension it is important to rule out pseudoresistant hypertension that may result from factors including poor blood pressure measurement technique and the white coat effect. Potential contributing factors should be identified and reversed if possible, including obesity, excess alcohol intake and use of interfering medications such as NSAIDS, sympathomimetics and oral contraceptives. Modification of lifestyle factors such as weight loss, sodium restriction and physical activity is paramount for treatment success. Secondary causes of hypertension are common in this patient group and, therefore, appropriate screening tests should be carried out as necessary. Pharmacologic therapy is centered on combination therapy of medications from different mechanisms of action, especially diuretics, which are essential in maximizing antihypertensive effects. The role of mineralocorticoid antagonists is expanding, especially in patients with obstructive sleep apnea and obesity where aldosterone excess may be implicated. Finally, when appropriate, specialist referral may facilitate blood pressure reduction and the ability to meet target blood pressure goals. [ABSTRACT FROM AUTHOR]