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BACKGROUND Obstructive sleep apnea (OSA), nocturnal hypertension, and nondipping systolic blood pressure (BP) are each highly prevalent among African Americans. However, few data are available on the association between OSA and nighttime BP in this population. METHODS We examined the association of OSA with nighttime BP among African Americans who completed 24-hour ambulatory BP monitoring (ABPM) at Exam 1 (2000–2004) of the Jackson Heart Study (JHS) and subsequently participated in the JHS Sleep Study (2012–2016). Type 3 home sleep apnea testing was used to assess OSA measures, including respiratory event index (REI4%) and percent sleep time RESULTS Among 206 participants who completed ABPM and participated in the Jackson Heart Sleep Study, 50.5% had nocturnal hypertension and 26.2% had moderate to severe OSA (REI4% ≥15 events/hour). After multivariable adjustment, each SD (13.3 events/hour) increase in REI4% was associated with 1.75 mm Hg higher nighttime DBP (95% confidence interval (CI): 0.38, 3.11) and a prevalence ratio of 1.11 (95% CI: 1.00, 1.24) for nocturnal hypertension. Each SD (10.4%) increase in nocturnal hypoxemia was associated with a 1.91 mm Hg higher nighttime SBP (95% CI: 0.15, 3.66). CONCLUSIONS Severity of OSA and nocturnal hypoxemia were associated with high nighttime BP in African American participants in the JHS.

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.

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.

SPRINT was a well designed and executed randomized clinical trial funded by the National Institutes of Health (NIH) in which 9,361 hypertensive patients at high risk of cardiovascular disease with blood pressure (BP) above 130 mm H g and below 180 mm H g, were randomly assigned to be treated to a goal systolic BP (SBP) of less than 140 vs. less than 120 mm Hg. The trial recruited hypertensive individuals in the United States who were older than 50 years of age and had never had a stroke and were not diabetic, but were either older than 75 years of age (28% of subjects), had chronic kidney disease with estimated glomerular filtration rate (eGFR) 20 m l/min/1.73 m 2 of body surface (28% of subjects), or had clinical or subclinical cardiovascular disease or a Framingham score indicating 10-year risk of >15% of cardiovascular disease. By 1-year post-randomization, the trial achieved SBPs of 121.4 mm H g in the intensive treatment group and 136.2 mm H g in the standard treatment group, a difference that was maintained throughout the trial. SPRINT was stopped early after a median follow-up of 3.26 years because of a 25% relative risk reduction in the intensive treatment group of the primary endpoint (myocardial infarction or other coronary syndromes, stroke, heart failure, or death from cardiovascular causes) and 27% in all-cause mortality. In order to achieve these results, patients in the intensive therapy group took a mean of approximately 3 vs. 2 antihypertensive drugs in the standard therapy group. About 3,000 patients in each group completed 3 years of the trial, a little more than 1,000 completed 4 and slightly less than 300 in each group completed 5 years of the trial. The beneficial results were found across all prespecified groups. However, it is noteworthy that individuals older than 75 years of age appeared to benefit more than younger subjects. Is it possible that these older individuals were “survivors,” who although at high cardiovascular risk, were able to benefit more than the more “mixed” younger group? As well, those subjects who entered the trial with SBP of

Abdominal obesity prevalence is increasing rapidly in the United States, particularly among adults 88 cm for women and >102 cm for men).2-5 High WC is associated with an increased risk of hypertension, stroke, coronary heart disease, diabetes mellitus, and cardiovascular-related death, independent of body mass index (BMI).6-11 Recognizing these important cardiovascular risks, the National Institutes of Health recommends screening for high WC in persons who are overweight (BMI 25–29.9) or obese class I (BMI 30–34.9) and to consider screening for high WC in persons with normal weight (BMI 18.5–24.9).2,4 However, many adults have moderate WC (80–88 cm for women and 94–102 cm for men).11-13 Less is known about the cardiovascular risks of moderate WC. Although WC appears to increase the risk of obesity-related complications in a graded fashion rather than only at high WC thresholds, previous studies have examined different moderate-range WC values based on empirically defined categories making translation of these findings into clinical practice challenging.8,9,14-15 Sex-specific WC cutoffs that predict obesity-related risk independent of BMI, that account for the graded relationship between WC and obesity-related risk, and that involve simple criteria (e.g., three strata) are needed for clinical practice and public health promotion. In 1995, Lean and colleagues identified two WC “action levels” associated with increased cardiovascular risk: (i) 80 cm in women and 94 cm in men, and (ii) 88 cm in women and 102 cm in men.14,16 However, few studies have tested whether these action levels predict cardiovascular risk independent of BMI in blacks and whites. The inclusion of blacks is important because US data (all pre-1990) have not found a consistent association between abdominal obesity and cardiovascular risk for blacks, after controlling for BMI.9,17,18 Therefore, we examined hypertension prevalence which is positively associated with obesity and abdominal obesity,2,6,19 by BMI and WC, with a focus on moderate WC, in a large biracial, national cohort of community-dwelling US adults aged 45–84 years. We tested the relationship between WC strata developed by Lean and colleagues and hypertension prevalence after adjusting for BMI and hypertension risk factors. We explored age variability because the relative proportion of lean body mass to fat mass may decrease with age7 and the relationship between abdominal obesity and cardiovascular risk may not persist in older adults after controlling for BMI.20 We hypothesized that moderate WC would be associated with prevalent hypertension among persons with normal, over-weight, or obese class I BMI.

Background Although insulin resistance and metabolic syndrome are often used synonymously, concordance is not established. Methods Metabolic, hemodynamic, and hormonal data were analyzed on 141 patients in the Trial of Preventing Hypertension (TROPHY) Sub-Study with high-normal blood pressure (BP) (130 to 139/85 to 89 mm Hg [mean ± SD, 133 ± 8/85 ± 6 mm Hg]; age, 48 ± 9 years; body mass index 30 ± 5 kg/m2). Results Fifty-three of 141 subjects (37.6%; ∼3/8) had the metabolic syndrome based on three or more of the five risk factors (BP, waist circumference, fasting triglycerides, HDL-cholesterol, glucose). To maintain consistency in proportions, insulin resistance was defined as the upper 3/8 of the distribution on the homeostatic model assessment (HOMA), which uses fasting glucose and insulin and a modified Matsuda-DeFronzo index, based on fasting, 1- and 2-h glucose and insulin values. Among metabolic syndrome patients, 57% and 55% were in the upper 3/8 of the distribution for insulin resistance by HOMA and Matsuda-DeFronzo, respectively. Among subjects without the metabolic syndrome, 26% and 27% were insulin resistant by HOMA and Matsuda-DeFronzo criteria. The proportion of patients with metabolic syndrome and insulin resistance increased strongly and similarly with increasing body mass index. However, metabolic syndrome and insulin resistance were different compared with their respective controls in the lower 5/8 of the distribution, in waist/hip ratios, fasting and 1-h insulin, HDL-cholesterol, heart rate, and systolic BP responses to exercise and plasma renin, angiotensin, and aldosterone. Conclusions The findings suggest that metabolic syndrome and insulin resistance are not synonymous anthropometrically, metabolically, hemodynamically, or hormonally in patients with high-normal BP.

Background Previous reports have demonstrated the antihypertensive efficacy of high doses of spironolactone in subjects with primary aldosteronism and, to a lesser degree, subjects with resistant hypertension. Methods In current analysis, we examined the antihypertensive benefit of adding low-dose spironolactone to multidrug regimens that included a diuretic and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in subjects with resistant hypertension with and without primary aldosteronism. Subjects referred for resistant hypertension were evaluated with an early morning plasma renin activity, 24-h urinary aldosterone and sodium during a high dietary salt ingestion. The diagnosis of primary aldosteronism was confirmed with a renin activity 12 μg/24 h and urinary sodium >200 mEq/24 h. After biochemical evaluation, spironolactone (12.5 to 25 mg/d) was added to each subject's antihypertensive regimen. If blood pressure (BP) remained uncontrolled, the dose of spironolactone was titrated up to 50 mg/d. Follow-up BP was determined at 6 weeks, 3 months, and 6 months. Results A total number of 76 subjects were included in the analysis, 34 of whom had biochemical primary aldosteronism. Low-dose spironolactone was associated with an additional mean decrease in BP of 21 ± 21/10 ± 14 mm Hg at 6 weeks and 25 ± 20/12 ± 12 mm Hg at 6-month follow-up. The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors, ARBs, and diuretics. Conclusions We conclude that low-dose spironolactone provides significant additive BP reduction in African American and white subjects with resistant hypertension with and without primary aldosteronism.

The calcium antagonists are effective in the treatment of essential hypertension. This quality, in addition to their ability to inhibit atherosclerotic lesion formation, may make them superior to other classes of antihypertensive agents in preventing vascular complications of mild to moderate hypertension. Preliminary results of clinical trials suggest that the calcium antagonists retard the progression of early atherosclerotic lesions in native coronary arteries and saphenous vein grafts, but have less effect on established lesions. Further study is needed to determine whether these agents have a favorable effect on the overall clinical outcome of patients with coronary artery disease. Clinical trials also suggest that the calcium antagonists retard the progression of renal insufficiency in hypertensive patients by mechanism(s) that do not depend on blood pressure lowering per se. Prospective studies with larger numbers of patients are needed to determine whether these apparent renoprotective effects are sustained for the long term in both diabetic and nondiabetic hypertensive populations. The dihydropyridine calcium antagonists are effective in reducing brain damage and mortality secondary to acute ischemic stroke. It is still unknown whether they are also effective in the primary and secondary prevention of ischemic stroke, and whether other classes of calcium antagonists are useful in the prevention and/or treatment of ischemic stroke. The potential antiatherosclerotic and cardio-, neuro-, and renoprotective effects of the calcium antagonists, coupled with their lack of adverse metabolic effects, have defined an expanding therapeutic role for these agents in the 1990s.

To identify antigens important to the diagnosis or pathogenesis of coccidioidomycosis, we analyzed three coccidioidal extracts by immunoblotting techniques with sera from patients infected with Coccidioides immitis and from immunized rabbits. When denatured fungal extracts were used, sera from at least 9 of 10 patients reacted with antigens of 100, 60, and 45 kilodaltons (kDa). By agar diffusion, the 100-kDa antigen appeared to be identical to the conventional tube precipitin antigen. Five of the six sera from patients with pulmonary syndromes reacted with another antigen of 70 kDa, but sera from patients with disseminated disease did not react with this antigen. Both the 100-kDa and the 70-kDa antigens were present in the 70-130-kDa region of the nondenatured fungal extracts. Our results suggest that the 100-kDa antigen may be useful in future diagnostic tests and that the 70-kDa antigen may identify patients whose infection is confined to the chest.