Celso Amodeo

Obstructive Sleep Apnea The Most Common Secondary Cause of Hypertension Associated With Resistant Hypertension

Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension may help to control blood pressure and reduce cardiovascular risk. However, there are no studies systematically evaluating secondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients with resistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, including aortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renal parenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age: 52±1 years, 43% males, systolic and diastolic blood pressure: 176±31 and 107±19 mm Hg, respectively), obstructive sleep apnea (apnea-hypopnea index: >15 events per hour) was the most common condition associated with resistant hypertension (64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified (primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age >50 years (odds ratio: 5.2 [95% CI: 1.9–14.2]; P<0.01), neck circumference ≥41 cm for women and ≥43 cm for men (odds ratio: 4.7 [95% CI: 1.3–16.9]; P=0.02), and presence of snoring (odds ratio: 3.7 [95% CI: 1.3–11]; P=0.02) were predictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea appears to be the most common condition associated with resistant hypertension. Age >50 years, large neck circumference measurement, and snoring are good predictors of obstructive sleep apnea in this population.

Disparate cardiovascular findings in men and women with essential hypertension

We measured systemic hemodynamic, volume, and endocrine findings in 100 hypertensive women matched to 100 men by mean arterial pressure, age, race, and body surface area. Women had a higher resting heart rate, cardiac index, and pulse pressure and lower total peripheral resistance (all p less than 0.01) than men with the same pressure level. Isometric stress caused an increase in arterial pressure that was almost 50% higher in men than in women. The sexual difference in cardiovascular findings was significant before but not after menopause. For any level of arterial pressure, total peripheral resistance (and therefore the risk of hypertensive cardiovascular disease) was lower in women than in men. We conclude that premenopausal women are hemodynamically younger than men of the same chronologic age. Our study identifies a pathophysiologic mechanism for the clinical and epidemiologic finding that essential hypertension is less lethal in women than in men.

Immediate and short-term hemodynamic effects of diltiazem in patients with hypertension.

The immediate effects of intravenous diltiazem effects and short-term (4 weeks) of the oral drug on systemic and regional hemodynamics, cardiac structure, and humoral responses were evaluated by previously reported methods in nine patients with mild-to-moderate essential hypertension and in one patient with primary aldosteronism. Diltiazem was first administered in three intravenous doses of 0.06, 0.06, and 0.12 mg/kg, respectively; patients were then treated for 4 weeks with daily doses ranging from 240 to 360 mg (average 300 mg). Intravenous diltiazem immediately reduced mean arterial pressure (from 115 +/- 3 to 96 +/- 3 mm Hg; p less than .01) through a fall in total peripheral resistance index (from 37 +/- 3 to 23 +/- 2 U/m2; p less than .01) that was associated with an increase in heart rate (from 66 +/- 2 to 77 +/- 3 beats/min; p less than .01) and cardiac index (from 3.3 +/- 0.3 to 4.3 +/- 0.4 liters/min/m2; p less than .01). These changes were not associated with changes in plasma levels of catecholamines or aldosterone or in plasma renin activity. After 4 weeks the significant decrease in mean arterial pressure persisted (104 +/- 3 mm Hg; p less than .01) and there were still no changes in the humoral substances or plasma volume. Renal blood flow index increased (from 368 +/- 52 to 462 +/- 57 ml/min/m2; p less than .01) and renal vascular resistance index decreased (from 0.37 +/- 0.06 to 0.26 +/- 0.04 U/m2; p less than .01), while splanchnic hemodynamics did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Biventricular cardiac hypertrophy in essential hypertension

Left ventricular hypertrophy (LVH) is the major adaptation of the heart to a prolonged increase in the left ventricular afterload in hypertension. However, the structure and function of the right ventricle have received little attention. The present study was designed to assess right ventricular structural changes in patients with established essential hypertension. To accomplish this, M-mode echocardiograms were obtained from 15 healthy normotensive subjects and 35 patients with essential hypertension-15 with normal left ventricles and 20 with clear-cut echocardiographic evidence of LVH. In comparison with the normotensive subjects, right ventricular wall thickness was increased almost twofold in the hypertensive patients with LVH (7.0 +/- 2.1 mm vs 3.7 +/- 0.8 mm; p less than 0.001); there was a significant, direct correlation between right and left ventricular wall thickness in the entire patient population (r = 0.65; p less than 0.001). Furthermore, the left atrial emptying index was significantly reduced in all patients with hypertension regardless of whether LVH was present (p less than 0.001) and suggests early diastolic functional involvement of the left ventricle in hypertension. We therefore conclude that right ventricular hypertrophy is associated with LVH in patients with hypertension, although the changes of LVH are frequently more obvious to the clinician.

Sarcopenia in chronic kidney disease on conservative therapy: prevalence and association with mortality

BACKGROUND In chronic kidney disease (CKD), multiple metabolic and nutritional abnormalities contribute to the impairment of skeletal muscle mass and function thus predisposing patients to the condition of sarcopenia. Herein, we investigated the prevalence and mortality predictive power of sarcopenia, defined by three different methods, in non-dialysis-dependent (NDD) CKD patients. METHODS We evaluated 287 NDD-CKD patients in stages 3-5 [59.9 ± 10.5 years; 62% men; 49% diabetics; glomerular filtration rate (GFR) 25.0 ± 15.8 mL/min/1.73 m(2)]. Sarcopenia was defined as reduced muscle function assessed by handgrip strength (HGS <30th percentile of a population-based reference adjusted for sex and age) plus diminished muscle mass assessed by three different methods: (i) midarm muscle circumference (MAMC) <90% of reference value (A), (ii) muscle wasting by subjective global assessment (B) and (iii) reduced skeletal muscle mass index (<10.76 kg/m² men; <6.76 kg/m² women) estimated by bioelectrical impedance analysis (BIA) (C). Patients were followed for up to 40 months for all-cause mortality, and there was no loss of follow-up. RESULTS The prevalence of sarcopenia was 9.8% (A), 9.4% (B) and 5.9% (C). The kappa agreement between the methods were 0.69 (A versus B), 0.49 (A versus C) and 0.46 (B versus C). During follow-up, 51 patients (18%) died, and the frequency of sarcopenia was significantly higher among non-survivors. In crude Cox analysis, sarcopenia diagnosed by the three methods was associated with a higher hazard for mortality; however, only sarcopenia diagnosed by method C remained as a predictor of mortality after multivariate adjustment. CONCLUSIONS The prevalence of sarcopenia in CKD patients on conservative therapy varies according to the method applied. Sarcopenia defined as reduced handgrip strength and low skeletal muscle mass index estimated by BIA was an independent predictor of mortality in these patients.

Diltiazem maintains renal vasodilation without hyperfiltration in hypertension: Studies in essential hypertensive man and the spontaneously hypertensive rat

SummaryThe systemic and renal hemodynamic effects of diltiazem were determined in patients with mild to moderately severe essential hypertension and in rats with spontaneous hypertension (SHR). Seven patients were treated for one full year (300 mg/day, average dose) and 10 SHR and 10 normotensive Wistar-Kyoto (WKY) rats received 1 and 2 mg/ kg, intravenously. In both man and rat with genetic hypertension, arterial pressure was reduced through a fall in total peripheral resistance without associated reflexive increases in heart rate and cardiac index; and the patients demonstrated no change in plasma volume. In both man and the SHR: renal blood flow increased (in SHR not statistically significant) as arterial pressure and renal vascular resistance fell; glomerular filtration rate (GFR) remained unchanged and the filtration fraction (FF) significantly fell; and calculated intrarenal hemodynamic indices (using the Gomez formulae) demonstrated falls in afferent and efferent glomerular arteriolar pressures and resistances and in intraglomerular pressures, thereby explaining the unchanged GFRs and the decline in FF. These findings in both hypertensive man and rat are in contrast with those of the normotensive WKY that only demonstrated a fall in afferent glomerular arteriolar resistance. Thus, these data demonstrate that diltiazem controlled arterial pressure in both forms of genetic hypertension associated with falls in systemic and renal arteriolar resistances and with improved intrarenal hemodynamics without glomerular hyperfiltration.

Obstructive sleep apnea, hypertension and cardiovascular diseases

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial (hypopnea) or complete interruption (apnea) in breathing during sleep due to airway collapse in the pharyngeal region. OSA and its cardiovascular consequences have been widely explored in observational and prospective studies. Most evidence verifies the positive relationship between OSA and hypertension, coronary artery disease, atrial fibrillation, stroke and heart failure. However, more studies are needed to better assess the impact of OSA, and possible benefit of treatment with continuous positive airway pressure (CPAP) on dyslipidemia, type 2 diabetes, insulin resistance and cardiovascular mortality. The leading pathophysiological mechanisms involved in the changes triggered by OSA, include intermittent hypoxemia and re-oxygenation, arousals and changes in intrathoracic pressure. Hypertension is strongly related with activation of the sympathetic nervous system, stimulation of the renin–angiotensin–aldosterone system and impairment of endothelial function. The high prevalence of OSA in the general population, hypertensive patients and especially obese individuals and patients resistant to antihypertensive therapy, highlights the need for effective screening, diagnosis and treatment of OSA to decrease cardiovascular risk.

National alert campaign about increased cholesterol: determination of cholesterol levels in 81,262 Brazilians

OBJECTIVE To determine the levels of total cholesterol in a significant sample of the Brazilian population. METHODS Blood cholesterol was determined in 81.262 individuals > 18 years old (51% male, 44.7 +/- 15.7 years), using Accutrend equipment, in the cities São Paulo, Campinas, Campos do Jordão, São José dos Campos, Santos, Santo André , Ribeirão Preto, Porto Alegre, Rio de Janeiro, Belo Horizonte, Curitiba, Brasília, Salvador and documented in the presence of other risk factors (RF) for coronary artery disease (CAD) (systemic hypertension, CAD in the family, smoking, and diabetes). Participants were classified according to sex, age, and the presence or absence of RF, respectively, as 0 RF, 1 RF and > 2 RF. The percentage of individuals with cholesterol > 200 mg/dL and > 240 mg/dL was evaluated. RESULTS The prevalence of individuals with 0, 1, and > 2 risk factors was 30% (n = 24,589), 36% (n =29,324), and 34% (n = 27,349) respectively, (P=0.657), and the mean total cholesterol of the population was 199.0 +/- 35.0 mg/dL. Cholesterol levels above 200 and 240 mg/dL were found, respectively, in 40% (n = 32,515) and 13% (10.942) of individuals. The greater the number of risk factors the higher the levels of cholesterol (P<0.0001) and the greater the proportion of individuals with cholesterol > 200 mg/dL (P=0.032). No difference existed in the proportion of individuals with cholesterol > 240 mg/dL (P=0.11). CONCLUSION A great percentage of individuals with cholesterol levels above those recommended to prevent coronary artery disease was found.

Visceral fat and coronary artery calcification in patients with chronic kidney disease

BACKGROUND Abdominal fat is a metabolically active tissue which has been associated with cardiovascular events and death in chronic kidney disease (CKD) patients. We explore here the association between surrogates of abdominal fat and coronary artery calcium score (CACs). METHODS Cross-sectional analysis of 232 non-dialysis-dependent CKD patients Stages 3-5 (median age 60 [25th-75th percentile 52-67] years; 60% men). Visceral adipose tissue (VAT) and CACs were assessed by computed tomography. Surrogates of abdominal fat included VAT and waist circumference (WC). RESULTS VAT was positively associated with CACs in univariate analysis (ρ = 0.23). Across increasing VAT quartiles, patients were older, more often men and smokers. Although increasing VAT quartiles associated with higher glomerular filtration rate and leptin, better nutritional status (subjective global assessment) as well as larger muscle stores and strength, they were also more insulin resistant (HOMA-IR), dyslipidemic and inflamed (C-reactive protein and white blood cells). In addition, CACs were incrementally higher. Clinically evident coronary artery calcification (CACs ≥ 10 Agatston) was present in 63% of the patients. Both increased visceral fat (odd ratio 1.60 [95% CI 1.23-2.09] per standard deviation increase) and increased WC (1.05 [1.01-1.12] per cm increase), augmented the odds to present calcification. Such associations remained statistically significant after extensive multivariate adjustment for confounders. CONCLUSIONS Abdominal fat is associated with coronary artery calcification in non-dialysis dependent CKD patients, supporting its potential role as a cardiovascular risk factor in uremia.

Comparison of diagnostic criteria for acute kidney injury in cardiac surgery

Background There is considerable controversy regarding the diagnosis of Acute Kidney Injury (AKI), and there are over 30 different definitions. Objective To evaluate the incidence and risk factors for the development of AKI following cardiac surgery according to the RIFLE, AKIN and KDIGO criteria, and compare the prognostic power of these criteria. Methods Cross-sectional study that included 321 consecutive patients (median age 62 [53-71] years; 140 men) undergoing cardiac surgery between June 2011 and January 2012. The patients were followed for up to 30 days, for a composite outcome (mortality, need for dialysis and extended hospitalization). Results The incidence of AKI ranged from 15% - 51%, accordingly to the diagnostic criterion adopted. While age was associated with risk of AKI in the three criteria, there were variations in the remaining risk factors. During follow-up, 89 patients developed the outcome and all criteria were associated with increased risk in the univariate Cox analysis and after adjustment for age, gender, diabetes, and type of surgery. However, after further adjustment for extracorporeal circulation and the presence of low cardiac output, only AKI diagnosed by the KDIGO criterion maintained this significant association (HR= 1.89 [95% CI: 1.18 - 3.06]). Conclusion The incidence and risk factors for AKI after cardiac surgery vary significantly according to the diagnostic criteria used. In our analysis, the KDIGO criterion was superior to AKIN and RIFLE with regard its prognostic power.