Gil F. Salles

Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus.

Background/Aims: Diabetic patients have an increased prevalence and severity of non‐alcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence and the factors associated with the presence of ultrasonographic NAFLD in type‐2 diabetic individuals.

Prognostic Influence of Office and Ambulatory Blood Pressures in Resistant Hypertension

BACKGROUND The prognostic value of office and ambulatory blood pressures (BPs) in patients with resistant hypertension is uncertain. METHODS This prospective study investigates the importance of office and ambulatory BPs as predictors of cardiovascular morbidity and mortality. At baseline, 556 resistant hypertensive patients underwent clinical-laboratory and 24-hour ambulatory BP monitoring examinations. Primary end points were a composite of fatal and nonfatal cardiovascular events and all-cause and cardiovascular mortalities. Multiple Cox regression was used to assess associations between BP and subsequent end points. RESULTS After median follow-up of 4.8 years, 109 patients (19.6%) reached the primary end point, and 70 all-cause deaths (12.6%) occurred (46 had cardiovascular causes). After adjustment for age, sex, body mass index, diabetes mellitus, smoking, physical inactivity, dyslipidemia, previous cardiovascular diseases, serum creatinine level, and number of antihypertensive drugs in use, no office BP showed any prognostic value. After further adjustment for office BP, higher mean ambulatory BPs were independent predictors of the composite end point. The hazard ratios associated with a 1-SD increment in daytime and nighttime systolic BP were 1.26 (95% confidence interval, 1.04-1.53) and 1.38 (1.13-1.68), respectively; the corresponding values for diastolic BP were 1.31 (1.05-1.63) and 1.36 (1.10-1.69). Ambulatory systolic and diastolic BP were equivalent predictors, and both were better than pulse pressure; nighttime BP was superior to daytime BP. For all-cause mortality, only the ambulatory BP monitoring diagnosis of true resistant hypertension was an independent predictor. CONCLUSION Higher ambulatory BP predicts cardiovascular morbidity and mortality in resistant hypertensive patients, whereas office BP has no prognostic value.

Efficacy of Spironolactone Therapy in Patients With True Resistant Hypertension

The role of spironolactone in resistant hypertension management is unclear. The aim of this prospective trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring. A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after a median interval of 7 months. Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration, and multivariate analysis adjusted for age, sex, and number of antihypertensive drugs to assess the predictors of blood pressure fall. There were mean reductions of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; P<0.001). Office systolic blood pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled ambulatory blood pressure was reached in 48% of patients. Factors associated with better response were higher waist circumference, lower aortic pulse wave velocity, and lower serum potassium. No association with plasma aldosterone or aldosterone:renin ratio was found. Adverse effects were observed in 13 patients (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect. In conclusion, spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure, especially in those with abdominal obesity and lower arterial stiffness. Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended.

Prognostic Value of Nocturnal Blood Pressure Reduction in Resistant Hypertension

BACKGROUND The prognostic value of nocturnal blood pressure (BP) reduction in resistant hypertension (RH) is unknown. The objective of this prospective study was to evaluate its importance as a predictor of cardiovascular morbidity and mortality. METHODS At baseline, 556 patients with RH underwent clinical and laboratory examinations and 24-hour ambulatory BP monitoring. The primary end points were a composite of fatal or nonfatal cardiovascular events, all-cause mortality, and cardiovascular mortality. Multiple Cox regression was used to assess associations between the nocturnal BP reduction and the subsequent end points. RESULTS After a mean follow-up of 4.8 years (range, 1-103 months), 109 patients (19.6%) reached the composite end point, with 70 all-cause and 46 cardiovascular deaths. A nondipping pattern was present in 360 patients (65.0%). After adjustment for age, sex, body mass index, diabetes, smoking status, physical inactivity, dyslipidemia, previous cardiovascular disease, number of antihypertensive drugs in use, and office and 24-hour ambulatory BP readings, the nondipping pattern was an independent predictor of the composite end point (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.12-2.71) and of cardiovascular mortality (HR, 2.31; 95% CI, 1.09-4.92). In subgroup analysis, the reduced (HR, 1.71; 95% CI, 1.03-2.83) and reverted (HR, 1.89; 95% CI, 1.04-3.43) dipping patterns were predictive of total cardiovascular events. The effect of the nondipping pattern on cardiovascular prognosis was stronger in younger patients and in those with true RH. CONCLUSIONS The nocturnal BP variability patterns provide valuable prognostic information for stratification of cardiovascular morbidity and mortality risk in patients with RH, above and beyond other traditional cardiovascular risk factors and mean ambulatory BP levels.

Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM). However, data regarding the prevalence and correlates of its histopathological stages are scarce. The aim was to investigate the prevalence and correlates of the more severe histopathological features of NAFLD, nonalcoholic steatohepatitis (NASH) and advanced fibrosis, in T2DM.

Prognostic Effect of the Nocturnal Blood Pressure Fall in Hypertensive Patients: The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) Meta-Analysis.

The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment ( P <0.001): untreated patients had increased risk of total CVEs (HR, 1.92), whereas treated patients had borderline lower risk (HR, 0.72) than normal dippers. For CVEs, heterogeneity was low for systolic night-to-day ratio and reverse/reduced dipping and moderate for extreme dippers. Quality of included studies was moderate to high, and publication bias was undetectable. In conclusion, in this largest meta-analysis of hypertensive patients, the nocturnal BP fall provided substantial prognostic information, independent of 24-hour SBP levels. # Novelty and Significance {#article-title-42}The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment (P<0.001): untreated patients had increased risk of total CVEs (HR, 1.92), whereas treated patients had borderline lower risk (HR, 0.72) than normal dippers. For CVEs, heterogeneity was low for systolic night-to-day ratio and reverse/reduced dipping and moderate for extreme dippers. Quality of included studies was moderate to high, and publication bias was undetectable. In conclusion, in this largest meta-analysis of hypertensive patients, the nocturnal BP fall provided substantial prognostic information, independent of 24-hour SBP levels.

Prognostic impact from clinic, daytime, and night-time systolic blood pressure in nine cohorts of 13,844 patients with hypertension.

Background and method: To determine which SBP measure best predicts cardiovascular events (CVEs) independently, a systematic review was conducted for cohorts with all patients diagnosed with hypertension, 1+ years follow-up, and coronary artery disease and stroke outcomes. Lead investigators provided ad hoc analyses for each cohort. Meta-analyses gave hazard ratios from clinic SBP (CSBP), daytime SBP (DSBP), and night-time SBP (NSBP). Coefficients of variation of SBP measured dispersion. Nine cohorts (n = 13 844) were from Europe, Brazil, and Japan. For sleep–wake SBP classification, seven cohorts used patient-specific information. Results: Overall, NSBPs dispersion exceeded DSBPs dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for CSBP and DSBP. For each comparison, P = 0.004 that this occurred by chance. Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals) = 1.25 (1.22–1.29), 1.20 (1.15–1.26), and 1.11 (1.06–1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20–1.31), 1.01 (0.94–1.08), and 1.00 (0.95–1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night–day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP: P = 0.023 and 0.012, respectively, that this occurred by chance. Conclusion: In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP, increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely.

Relation of Left Ventricular Hypertrophy With Systemic Inflammation and Endothelial Damage in Resistant Hypertension

The relation between left ventricular hypertrophy (LVH) and unfavorable cardiovascular prognosis may involve systemic inflammation and endothelial dysfunction/damage. The aim of this study was to investigate in a cross-sectional design the relationships of LVH with C-reactive protein (CRP) levels (a marker of systemic low-grade inflammation) and with microalbuminuria (a marker of glomerular endothelial damage) in 705 patients with resistant hypertension. At baseline, all were submitted to a laboratory evaluation including 24-hour urinary albumin excretion, 2D echocardiogram, and 24-hour ambulatory blood pressure monitoring. A total of 463 patients also had high-sensitivity CRP levels determined. LVH was defined as an indexed left ventricular mass >110 g/m2 in women and >125 g/m2 in men. Microalbuminuria was evaluated in 3 categories: low normal (<15 mg/24 hours), high normal (between 15 and 29 mg/24 hours), and abnormal (between 30 and 299 mg/24 hours). CRP was dichotomized at the median value (3.7 mg/L). Associations with LVH were examined after adjustment for all of the potential confounders by multivariate logistic regression. A total of 534 patients (75.7%) had LVH. After full adjustment, both abnormal microalbuminuria (odds ratio: 1.97; 95% CI: 1.04 to 3.73) and high CRP (OR: 1.76; 95% CI: 1.06 to 2.93) were independently associated with LVH occurrence. The high-normal albuminuria was associated with a borderline significant 46% increased chance of having LVH. Furthermore, the association between high CRP and LVH was observed exclusively in the subgroup with normal albuminuria. In conclusion, both systemic inflammation and endothelial damage were associated with LVH occurrence. These relationships offer insight into the pathophysiological mechanisms linking LVH to atherosclerosis and to increased cardiovascular morbidity and mortality.

Prognostic value of QT interval parameters in type 2 diabetes mellitus: Results of a long-term follow-up prospective study

The prognostic importance of electrocardiographic ventricular repolarization QT parameters (maximum rate-corrected QT interval-QTcmax, QT interval dispersion-QTd, and QTcd), in relation to other risk markers, on cardiovascular and cardiac mortality, and on total fatal or nonfatal cardiovascular events, was evaluated prospectively in 471 type 2 diabetic outpatients. During a median follow-up of 57 months (range: 2-84), 121 (25.7%), patients died, 44 (36.3% of them) from cardiovascular causes and 106 (22.5%) fatal or nonfatal cardiovascular events were observed. In Cox proportional hazards multivariate analysis, both QTd and QTcmax were independent predictors of cardiovascular and cardiac mortality (hazard ratio [HR]: 1.34, 95% confidence interval [95% CI]: 1.12-1.59, for each 10-ms increments in QTd and HR: 1.17, 95% CI: 1.03-1.21 for 10-ms increments in QTcmax, for cardiovascular mortality). They were also predictors of total fatal or nonfatal cardiac and cardiovascular events (HR: 1.18, 95% CI: 1.05-1.33 for QTd and HR: 1.09, 95% CI: 1.04-1.15 for QTcmax). Additional independent prognostic markers for total cardiovascular events were the presence of previous cardiac disease, cerebral or peripheral vascular disease, age, male gender, known diabetes duration, heart rate, and serum triglycerides. Excluding patients with prior cardiac disease did not change significantly the prognostic performance of QTd but decreased that of QTcmax. In conclusion, QT interval parameters give additional prognostic information in patients with type 2 diabetes mellitus, beyond that obtained from traditional risk factors. QT interval dispersion seems a better prognostic marker than maximum QT interval, particularly in patients without previous cardiac diseases.

Microvascular degenerative complications are associated with increased aortic stiffness in type 2 diabetic patients

OBJECTIVE Diabetes is a risk factor for increased arterial stiffness; however, few studies had investigated its associated factors. The aim was to evaluate the correlates of increased arterial stiffness in type 2 diabetes, particularly the relationships with microvascular complications. METHODS 482 type 2 diabetic patients without peripheral arterial disease were evaluated in a cross-sectional study. Clinical (including tests of cardiovascular dysautonomy), laboratory, ECG, echocardiographic and 24h ambulatory blood pressure monitoring data were obtained. Arterial stiffness was assessed by carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocity (PWV) measurements. Statistics included multivariate linear and logistic regressions to investigate the independent correlates of increased arterial stiffness. RESULTS No diabetes-related variable was associated with peripheral arterial stiffness. 148 patients (31%) had increased aortic PWV (>12m/s). On multiple linear regression, retinopathy and nephropathy, besides age, heart rate, 24h pulse pressure, diabetes duration, dyslipidemia and number of antihypertensive drugs in use, were independently associated with aortic PWV. On multivariate logistic regression increased aortic stiffness was associated with retinopathy (odds ratio: 3.83, 95% confidence interval [CI]: 2.24-6.56, p<0.001) and peripheral neuropathy (odds ratio: 1.79, 95%CI: 1.06-3.02, p=0.03) after adjusting for possible confounding variables. Other variables associated with increased aortic stiffness were older age, heart rate, diabetes duration, 24h pulse pressure, dyslipidemia and physical inactivity. CONCLUSIONS In type 2 diabetic patients, increased central arterial stiffness is associated with the presence of microvascular complications independent of other established determinants of aortic stiffness.