Refractory Hypertension: a Narrative Systematic Review with Emphasis on Prognosis.

PURPOSE OF REVIEW: To perform a narrative systematic review on refractory hypertension (RfHT) with particular emphasis on prognosis. RECENT FINDINGS: There were 37 articles on RfHT, 13 non-systematic reviews, and 24 original studies. RfHT, a recently described extreme phenotype of anti-hypertensive treatment failure, shall be defined as uncontrolled out-of-office blood pressure (BP) levels despite the use of at least 5 anti-hypertensive drugs, including a long-acting diuretic and a mineraloreceptor antagonist. Its prevalence ranges from 0.5 to 4.3% of general treated hypertensives and between 3.6 and 51.4% of patients with resistant hypertension (RHT). RfHT is associated with younger age, African ancestry, obesity, hypertension-mediated organ damage and clinical cardiovascular diseases, and with some comorbidities, such as diabetes and obstructive sleep apnea. Its physiopathological mechanisms probably involve sympathetic overactivity and not volume overload. Patients with RfHT have a worse prognosis than non-refractory RHT individuals, with higher risks of adverse cardiovascular and renal outcomes and of mortality. RfHT represents a rare but true extreme phenotype of anti-hypertensive treatment failure distinct from RHT and with a significantly worse prognosis. Identifying such individuals is important to tailor specific interventions.

Prevalence and associated factors of aspiration and severe dysphagia in asymptomatic patients in the late period after open partial laryngectomy: a videofluoroscopic evaluation.

PURPOSE: This study aimed to evaluate late and asymptomatic patients after open partial horizontal laryngectomy (OPHL), investigating the clinical-surgical and socio-demographic factors associated with aspiration and severe dysphagia. METHODS: One-thousand videofluoroscopic swallowing studies were performed in 100 asymptomatic patients in the late period after OPHL(median 6.5 years). Aspiration and severe dysphagia were, respectively, assessed by the Penetration-Aspiration scale (PAS) and by the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) classification. Associated factors were investigated by multivariate logistic regressions. RESULTS: 34% (95% CI 24.3-47.6%) of patients presented aspiration and 23% (95% CI 15.3-34.6%) had severe or life-threatening dysphagia (DIGEST grades 3-4). On logistic regression, the presence of aspiration was associated with lower preoperative serum albumin (odds ratio [OR]: 0.22; 95% CI 0.07-0.64; p = 0.005, for each 1 g/dL increment); a greater weight loss in early postoperative period (OR: 1.19, 95% CI 1.05-1.35; p = 0.008, for each 1 kg loss); older age at surgery (OR: 1.08; 95% CI 1.01-1.17, for each 1-year older); and with the presence of diabetes (OR: 5.16; 95% CI 1.09-27.47; p = 0.039). CONCLUSION: Deglutition abnormalities are frequent in asymptomatic patients later after OPHL. Older patients, with lower preoperative serum albumin levels, with greater postoperative weight loss, and with diabetes compose the clinical profile at risk for having worse swallowing function in the late period after OPHL.

Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

BACKGROUND: The prognostic importance of several hematological parameters has been scarcely investigated in type 2 diabetes. So, we aimed to evaluate their prognostic importance for development of complications in a cohort of type 2 diabetes. METHODS: In a prospective study, 689 individuals with type 2 diabetes had blood red cell, platelet and leukocyte parameters obtained at baseline. Multivariate Cox analyses examined the associations between several hematological parameters (including neutrophyl-to-lymphocyte, lymphocyte-to-monocyte, platelet-to-lymphocyte, and monocyte-to-HDL ratios) and the occurrence of microvascular (retina, renal and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs], and major adverse CVEs [MACEs]), and all-cause and cardiovascular mortality. Improvements in risk discrimination were assessed by C-statistics and Integrated Discrimination Improvement (IDI) index. RESULTS: During a median follow-up of 10.5 years, 212 patients had a CVE (174 MACEs), 264 patients died (131 cardiovascular deaths); 206 had a renal, 161 a retinopathy and 179 patients had a neuropathy outcome. In multivariate-adjusted analyses, the lymphocytes count and lymphocyte-to-monocyte ratio were protective (hazard ratios [HRs]: 0.77 and 0.72, respectively), whereas the neutrophyl-to-lymphocyte and platelet-to-lymphocyte ratios were associated with increased risks (HRs: 1.19 and 1.17) for all-cause mortality. For cardiovascular mortality, the monocytes count, the neutrophyl-to-lymphocyte and monocyte-to-HDL ratios were associated with increased risks and the lymphocyte-to-monocyte ratio was protective. Higher lymphocyte-to-monocyte ratio was protective for renal failure outcome. However, none of them improved risk discrimination. CONCLUSIONS: Low lymphocytes count and leukocyte ratios that mainly included lymphocytes were predictors of macrovascular complications and mortality in individuals with type 2 diabetes. However, they did not improve risk prediction over traditional risk factors.

Prognostic impact of liver fibrosis and steatosis by transient elastography for cardiovascular and mortality outcomes in individuals with nonalcoholic fatty liver disease and type 2 diabetes: the Rio de Janeiro Cohort Study.

BACKGROUND: Liver stiffness measurement (LSM, which reflects fibrosis) and controlled attenuation parameter (CAP, which reflects steatosis), two parameters derived from hepatic transient elastography (TE), have scarcely been evaluated as predictors of cardiovascular complications and mortality in individuals with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). METHODS: Four hundred type 2 diabetic patients with NAFLD had TE examination (by Fibroscan®) performed at baseline. Multivariate Cox analyses evaluated the associations between TE parameters and the occurrence of cardiovascular events (CVEs) and mortality. TE parameters were assessed as continuous variables and dichotomized at low/high values reflecting advanced liver fibrosis (LSM > 9.6 kPa) and severe steatosis (CAP > 296 or > 330 dB/m). Improvements in risk discrimination were assessed by C-statistic and by the relative Integrated Discrimination Improvement (IDI) index. RESULTS: During a median follow-up of 5.5 years, 85 patients died (40 from cardiovascular causes), and 69 had a CVE. As continuous variables, an increasing LSM was a risk marker for total CVEs (hazard ratio [HR]: 1.05; 95% CI: 1.01-1.08) and all-cause mortality (HR: 1.04; 95% CI: 1.01-1.07); whereas an increasing CAP was a protective factor for both outcomes (HR: 0.93; 95% CI: 0.89-0.98; and HR: 0.92; 95% CI: 0.88-0.97; respectively). As dichotomized variables, a high LSM remained a risk marker of adverse outcomes (with HRs ranging from 2.5 to 3.0) and a high CAP was protective (with HRs from 0.3 to 0.5). The subgroup of individuals with low-LSM/high-CAP had the lowest risks while the opposite subgroup with high-LSM/low-CAP had the highest risks. Both LSM and CAP improved risk discrimination, with increases in C-statistics up to 0.037 and IDIs up to 52%. CONCLUSIONS: Measured by hepatic TE, advanced liver fibrosis is a risk marker and severe steatosis is a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD.

Traditional and non-traditional risk factors for peripheral artery disease development/progression in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

BACKGROUND: The prognostic importance of non-traditional risk factors for peripheral artery disease (PAD) development/progression is scarcely studied in diabetes. We investigated if carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) added prognostic information beyond traditional cardiovascular risk markers for PAD outcomes. METHODS: Ankle-brachial index (ABI) was measured at baseline and after a median of 91 months of follow-up in 681 individuals with type 2 diabetes. Multivariate Cox regressions examined the associations between the candidate variables and the outcome. PAD development/progression was defined by a reduction in ABI ≥ 0.15 (to a level < 0.9) or limb revascularization procedures, lower-extremity amputations or death due to PAD. The improvement in risk discrimination was assessed by increases in C-statistics of the models. RESULTS: Seventy-seven patients developed/progressed PAD: 50 reduced ABI to < 0.9, seven had lower-limb revascularizations, and 20 had amputations or death. Age, male sex, diabetes duration, presence of microvascular complications (peripheral neuropathy and diabetic kidney disease), baseline HbA1c, 24-h systolic BP (SBP) and mean cumulative office SBP and LDL-cholesterol were associated with PAD development/progression in several models. CIMT and cf-PWV were additionally associated with PAD outcomes, and their inclusion further improved risk discrimination (with C-statistic increases between 0.025 and 0.030). The inclusion of ambulatory 24-h SBP, instead of office SBP, also improved PAD risk discrimination. CONCLUSIONS: Increased CIMT and aortic stiffness are associated with greater risks of developing/progressing PAD, beyond traditional risk factors, in type 2 diabetes.

Prognostic importance of visit-to-visit blood pressure variability for micro- and macrovascular outcomes in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study.

BACKGROUND: The prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes. METHODS: BP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index. RESULTS: Over a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03-1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%). CONCLUSIONS: Systolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.

Effects of continuous positive airway pressure treatment on aortic stiffness in patients with resistant hypertension and obstructive sleep apnea: A randomized controlled trial.

Resistant hypertension (RHT) is associated with obstructive sleep apnea (OSA) and increased aortic stiffness, measured by carotid-femoral pulse wave velocity (cf-PWV). We aimed to evaluate in a randomized controlled trial, the effect of Continuous positive airway pressure (CPAP) treatment on cf-PWV in comparison with a control group in patients with RHT and moderate-severe OSA. One-hundred and sixteen patients were randomized to 6-month CPAP treatment (56 patients) or no therapy (60 patients), while keeping their antihypertensive treatment unchanged. Carotid-femoral pulse wave velocity was performed at the beginning and end of the 6-month period. Intention-to-treat intergroup differences in cf-PWV changes were assessed by a generalized mixed-effects model with the allocation group as a fixed factor and adjusted for age, sex, changes in mean arterial pressure and the baseline cf-PWV values. Subgroup sensitivity analyses were performed, excluding patients with low CPAP adherence and low cf-PWV at baseline. CPAP and control groups had similar clinic-laboratorial characteristics. Patients had a mean cf-PWV of 9.4 ± 1.6 m/s and 33% presented cf-PWV > 10 m/s. During treatment, the control group had a mean increase in cf-PWV of +0.43 m/s (95% confidence interval [CI], +0.14 to +0.73 m/s; p = .005), whereas the CPAP group had a mean increase of +0.03 m/s (95% CI, -0.33 to +0.39 m/s; p = .87), resulting in a mean difference in changes between CPAP and control of -0.40 m/s (95% CI, -0.82 to +0.02 m/s; p = .059). Subgroup analyses did not change the results. In conclusion, a 6-month CPAP treatment did not reduce aortic stiffness, measured by cf-PWV, in patients with RHT and moderate/severe OSA, but treatment may prevent its progression, in contrast to no-CPAP therapy.

Prognostic impact of carotid intima-media thickness and carotid plaques on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

BACKGROUND: The prognostic importance of carotid atherosclerosis in individuals with diabetes is unsettled. We aimed to evaluate the relationships between parameters of carotid atherosclerosis and the future occurrence of micro- and cardiovascular complications in individuals with type 2 diabetes. METHODS: Ultrasonographic parameters of carotid atherosclerosis, intima-media thickness (CIMT) and plaques, were measured at baseline in 478 participants who were followed-up for a median of 10.8 years. Multivariate Cox analysis was used to examine the associations between carotid parameters and the occurrence of microvascular (retinopathy, renal, and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs] and cardiovascular mortality), and all-cause mortality. The improvement in risk stratification was assessed by using the C-statistic and the integrated discrimination improvement (IDI) index. RESULTS: During follow-up, 116 individuals had a CVE and 115 individuals died (56 from cardiovascular diseases); 131 newly-developed or worsened diabetic retinopathy, 156 achieved the renal composite outcome (94 newly developed microalbuminuria and 78 deteriorated renal function), and 83 newly-developed or worsened peripheral neuropathy. CIMT, either analysed as a continuous or as a categorical variable, and presence of plaques predicted CVEs occurrence and renal outcomes, but not mortality or other microvascular complications. Individuals with an increased CIMT and plaques had a 1.5- to 1.8-fold increased risk of CVEs and a 1.6-fold higher risk of renal outcome. CIMT and plaques modestly improved cardiovascular risk discrimination over classic risk factors, with IDIs ranging from 7.8 to 8.4%; but more markedly improved renal risk discrimination, with IDIs from 14.8 to 18.5%. CONCLUSIONS: Carotid atherosclerosis parameters predicted cardiovascular and renal outcomes, and improved renal risk stratification. Ultrasonographic carotid imaging may be useful in type 2 diabetes management.

Efficacy of diacerein in reducing liver steatosis and fibrosis in patients with type 2 diabetes and non-alcoholic fatty liver disease: A randomized, placebo-controlled trial.

The aim was to assess, in a randomized, double-blinded, placebo-controlled trial, the efficacy of diacerein, an anti-inflammatory drug, in improving liver fibrosis and steatosis in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sixty-nine diabetic patients with NAFLD were randomized to 24-month treatment with placebo (35 patients) or diacerein 100 mg/day (34 patients). Liver stiffness and steatosis were assessed by transient elastography (Fibroscan®) at baseline, and 12 and 24 months of follow-up. The primary outcome was the difference in mean liver stiffness and steatosis changes during treatment. Adjusted differences in mean changes on intention-to-treat analyses were estimated by generalized repeated-measures mixed-effects regressions. Diacerein significantly reduced liver stiffness in contrast to placebo by 1.6 kPa (95% CI: -2.6 to -0.5 kPa; p = 0.003), whereas no significant difference in mean changes in liver steatosis was observed. The reduction in liver stiffness was already evident at the 12-month examination, and accentuated at the 24-month examination. Eight patients reduced liver fibrosis stage during treatment, seven of whom were in the diacerein group (p = 0.020). In conclusion, a 2-year treatment with diacerein significantly reduced liver fibrosis in diabetic patients with NAFLD.

PNPLA3 gene polymorphism in Brazilian patients with type 2 diabetes: A prognostic marker beyond liver disease?

BACKGROUND & AIMS: Genetic factors may impact nonalcoholic fatty liver disease (NAFLD) severity. We aimed to assess the prevalence of patatin-like phospholipase domain-containing 3 protein (PNPLA3) gene rs738409 C > G polymorphism in Brazilian individuals with type 2 diabetes and to investigate its association with liver disease severity, diabetic chronic degenerative complications, and metabolic control. METHODS AND RESULTS: PNPLA3 genotyping was performed and classified as CC, CG, and GG. Clinical and laboratory data were obtained, including chronic degenerative diabetes complications. Liver stiffness and steatosis were evaluated by transient hepatic elastography with CAP using FibroScan®. Multiple logistic regression was performed to investigate the association of PNPLA3 G allele with clinical and laboratory variables and with hepatic fibrosis/steatosis. Three hundred three patients were included (118 male, mean age 59 ± 9.5 years). The G allele frequency was 32.5% (CC 47%, CG 41%, and GG 12%). Significant liver fibrosis and severe steatosis were diagnosed in 26% and 43% of patients, respectively. The variables independently associated with the G allele were coronary artery disease (OR: 2.25; 95% CI: 1.03-4.88; p = 0.04), better glycemic control (OR for having an HbA1c ≥ 8% [64 mmol/mol]: 0.53; 95% CI: 0.31-0.89; p = 0.01), and significant liver fibrosis (OR: 1.82; 95% CI: 1.04-3.17; p = 0.03). CONCLUSION: In individuals with diabetes and NAFLD, PNPLA3 gene rs738409 C > G polymorphism is a marker for the risk of significant liver fibrosis and cardiovascular disease and may be associated with better glycemic control.

Prognostic impact of the ankle-brachial index on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study.

AIMS/HYPOTHESIS: The prognostic importance of the ankle-brachial index (ABI) in individuals with diabetes is controversial. We aimed to evaluate the relationship between the ABI and the occurrence of micro- and macrovascular complications in individuals with type 2 diabetes. METHODS: The ABI was measured at baseline in 668 individuals with type 2 diabetes, and the individuals were followed-up for a median of 10 years. Multivariate Cox analysis was used to examine associations between the ABI and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration and peripheral neuropathy) and macrovascular (total cardiovascular events, major adverse cardiovascular events [MACE] and cardiovascular mortality) complications, and all-cause mortality. The improvement in risk stratification was assessed using the C statistic and the integrated discrimination improvement (IDI) index. RESULTS: During follow-up, 168 individuals had a cardiovascular event (140 MACE) and 191 individuals died (92 cardiovascular deaths); 156 individuals newly developed or experienced worsening diabetic retinopathy, 194 achieved the renal composite outcome (122 with newly developed microalbuminuria and 93 with deteriorating renal function) and 95 newly developed or experienced worsening peripheral neuropathy. The ABI, either analysed as a continuous or as a categorical variable, was significantly associated with all macrovascular and mortality outcomes, except for non-cardiovascular mortality. Individuals with a baseline ABI of ≤0.90 had a 2.1-fold increased risk of all-cause mortality (95% CI 1.3, 3.5; p = 0.004), a 2.7-fold excess risk of cardiovascular mortality (95% CI 1.4, 5.4; p = 0.004) and a 2.5-fold increased risk of MACE (95% CI 1.5, 4.4; p = 0.001). The ABI improved risk discrimination over classical risk factors, with relative IDIs ranging from 6.3% (for all-cause mortality) to 31% (for cardiovascular mortality). In addition, an ABI of ≤0.90 was associated with the development or worsening of peripheral neuropathy (2.1-fold increased risk [95% CI 1.1, 4.3]; p = 0.033), but not with retinopathy or renal outcomes. CONCLUSIONS/INTERPRETATION: A low ABI is associated with excess risk of adverse cardiovascular outcomes, mortality and peripheral neuropathy development or worsening, and improves cardiovascular risk stratification. The ABI should therefore be routinely evaluated in individuals with type 2 diabetes.

Aortic stiffness and ambulatory blood pressure as predictors of diabetic kidney disease: a competing risks analysis from the Rio de Janeiro Type 2 Diabetes Cohort Study.

AIMS/HYPOTHESIS: Diabetic kidney disease (DKD) is a microvascular complication associated with poor control of blood glucose and BP. We aimed to evaluate the predictors of development and progression of DKD in a cohort of high-risk individuals with type 2 diabetes, placing emphasis on ambulatory BP and arterial stiffness. METHODS: In a prospective study, 629 individuals without advanced renal failure had their renal function evaluated annually over a median follow-up period of 7.8 years. Ambulatory BP was monitored and aortic stiffness was assessed by carotid-femoral pulse wave velocity at baseline. Multivariate competing risks analysis with all-cause mortality, using the Fine and Gray approach, was used to examine the independent predictors of development and progression of DKD, a composite of development or progression of abnormal albuminuria and worsening of renal function (doubling of serum creatinine or progression to end-stage renal disease). RESULTS: At baseline, 197 individuals had DKD. During follow-up, DKD developed or progressed in 195 individuals, abnormal albuminuria developed or progressed in 125 individuals and renal function deteriorated in 91. After adjustments for baseline albuminuria and renal function, age, sex, diabetes duration and use of renin-angiotensin antagonists, poorer control of blood glucose (HR 1.17; 95% CI 0.98, 1.40; p = 0.09 for each 1 SD increment in mean first-year HbA1c), higher ambulatory systolic BP (HR 1.28; 95% CI 1.09, 1.50; p = 0.003, for each 1 SD increase in daytime systolic BP [SBP]) and increased aortic stiffness (HR 1.16; 95% CI 1.00, 1.34; p = 0.05) were independent predictors of development or progression of DKD. At baseline, ambulatory BP was a stronger predictor than BP measured in the clinic. Aortic stiffness predicted abnormal albuminuria development or progression (HR 1.26; 95% CI 1.02, 1.56; p = 0.036) whereas ambulatory BP was a stronger predictor of renal function deterioration (HR 1.32; 95% CI 1.09, 1.60; p = 0.005 for daytime SBP). CONCLUSIONS/INTERPRETATION: Poor blood glucose and BP control and increased aortic stiffness were the main predictors of development or progression of DKD; ambulatory SBP was a better predictor than BP measured in the clinic. Ambulatory BP monitoring and assessment of aortic stiffness should be more widely used in clinical type 2 diabetes management.

Increasing aortic stiffness is predictive of advanced liver fibrosis in patients with type 2 diabetes: the Rio-T2DM cohort study.

BACKGROUND & AIMS: Type 2 diabetes mellitus (T2DM) is a risk factor for cardiovascular disease (CVD) and advanced stages of non-alcoholic fatty liver disease (NAFLD). The aim was to evaluate the association between aortic stiffness, a preclinical CVD marker, with advanced liver fibrosis identified by transient elastography (TE) in T2DM outpatients with NAFLD. METHODS: This longitudinal study included 291 T2DM patients with NAFLD detected by ultrasonography, who had two carotid-femoral pulse wave velocity (cf-PWV) measurements and a TE examination (Fibroscan(®) ) performed over a median follow-up of 7 years. Advanced liver fibrosis (corresponding to ≥ F3 stage) was considered as median values >7.9 kPa (M probe) or >7.2 kPa (XL probe). Increased aortic stiffness was defined as cf-PWV >10 m/s. RESULTS: Eighty patients (27.5%) had advanced liver fibrosis. Overall, there was an increase in cf-PWV of 0.1 m/s/year (1% per year). Both a high aortic stiffness at the 2nd cf-PWV examination [odds ratios (OR): 3.0; 95% CI: 1.3-7.2; P = 0.011] and a serial increase in aortic stiffness (OR: 2.1; 95% CI: 1.0-4.3; P = 0.046) were associated with increased odds of having advanced liver fibrosis. Patients who presented either an increase in aortic stiffness or persisted with high values had significantly higher mean liver stiffness than those who either decreased aortic stiffness or persisted with normal cf-PWV values (mean difference: 2.1 kPa, 95% CI: 0.5-3.7 kPa, P = 0.012), after adjustments for anthropometric-demographic and clinical laboratory covariates. CONCLUSIONS: In T2DM patients with NAFLD, a high or increasing aortic stiffness predicted development of advanced liver fibrosis on TE.

Prognostic Importance of Ambulatory Blood Pressure Monitoring in Resistant Hypertension: Is It All that Matters?

PURPOSE OF REVIEW: This article reviews the current knowledge on the prognostic importance of ambulatory blood pressure (BP) monitoring parameters in patients with apparent treatment-resistant hypertension. RECENT FINDINGS: Although mean 24-h ambulatory BPs have been consistently established as better cardiovascular risk predictors than clinic (office) BPs in several clinical settings, and ambulatory BP monitoring is generally indicated in patients with resistant hypertension; there were only five previous longitudinal prospective studies that specifically evaluated the prognostic importance of ambulatory BP monitoring parameters in resistant hypertensive patients. These studies are carefully reviewed here. In conjunction, they demonstrated that office BP levels have little, if any, prognostic value in resistant hypertensive patients. Otherwise, several ambulatory BP monitoring parameters are strong cardiovascular risk predictors, particularly nighttime sleep BPs and the non-dipping pattern. Most relevant, the ambulatory BP monitoring diagnosis of true resistant hypertension (i.e., patients with uncontrolled ambulatory BPs, either daytime or nighttime) doubled the risk of future occurrence of major cardiovascular events in contrast to patients with white-coat resistant hypertension (i.e., with controlled ambulatory BPs despite uncontrolled office BPs). This review reinforces the pivotal role of serial ambulatory BP monitoring examinations in the clinical management of patients with resistant hypertension.

Are 2 Years Enough? Exploring Technical Skills Acquisition Among General Surgery Residents in Brazil.

UNLABELLED: Phenomenon: Recent studies have shown that up to 40% of the General Surgery (GS) residents are not confident with their surgical skills. There is concern that residents are at risk of receiving inadequate training due to the low number of operations they perform. In Brazil, although all GS residents receive by law the Board Certification at the end of their programs, the assessment of their technical skills is not mandatory in Medical Residency programs' training. Consequently, our concern was that current GS medical residency format might be insufficient to create competent and autonomous general surgery residents after 2 years of regular training. Hence, the aim was to assess GS residents' surgical skills in their final months of training to evaluate the present format of GS residency programs in Brazil. APPROACH: Trained surgical faculty members directly observed 11 operations of varying difficulty performed by 2nd-year regular GS residents and by 4th-year residents in the optional Advanced Program in General Surgery. Participants were located at 3 university and 3 nonuniversity hospitals in Rio de Janeiro and Sao Paulo (Brazil's largest cities). Surgical skills were assessed using an internally developed observation checklist reviewed by subject matter experts. FINDINGS: Sixty residents (46 regular 2nd-year trainees and 14 advanced 4th-year trainees) were assessed on performing 499 operations. Only 10 residents (17%), all advanced 4th-year residents, satisfactorily performed all operations and were considered eligible for the Board Certification. Even after excluding the 2 operations of greatest difficulty, only 24 regular 2nd-year residents (52%) satisfactorily performed the other 9 operations. Residents from hospitals with open Emergency Departments performed better than those from hospitals without Emergency Departments. Insights: The results of this pilot study suggest that residents with 2 years of training are not prepared for independent high-level surgical practice. The current formatting of regular GS residency programs in Brazil (2 years) may be insufficient to train experts in general surgery.

Aortic Stiffness as a Surrogate Endpoint to Micro- and Macrovascular Complications in Patients with Type 2 Diabetes.

Increased aortic stiffness has been recognized as a predictor of adverse cardiovascular outcomes in some clinical conditions, such as in patients with arterial hypertension and end-stage renal disease, in population-based samples and, more recently, in type 2 diabetic patients. Patients with type 2 diabetes have higher aortic stiffness than non-diabetic individuals, and increased aortic stiffness has been correlated to the presence of micro- and macrovascular chronic diabetic complications. We aimed to review the current knowledge on the relationships between aortic stiffness and diabetic complications, their possible underlying physiopathological mechanisms, and their potential applications to clinical type 2 diabetes management.

NAFLD and Increased Aortic Stiffness: Parallel or Common Physiopathological Mechanisms?

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide. Liver inflammation and fibrosis related to NAFLD contribute to disease progression and increasing liver-related mortality and morbidity. Increasing data suggest that NAFLD may be linked to atherosclerotic vascular disease independent of other established cardiovascular risk factors. Central arterial stiffness has been recognized as a measure of cumulative cardiovascular risk marker load, and the measure of carotid-femoral pulse wave velocity (cf-PWV) is regarded as the gold standard assessment of aortic stiffness. It has been shown that increased aortic stiffness predicts cardiovascular morbidity and mortality in several clinical settings, including type 2 diabetes mellitus, a well-known condition associated with advanced stages of NAFLD. Furthermore, recently-published studies reported a strong association between NAFLD and increased arterial stiffness, suggesting a possible link in the pathogenesis of atherosclerosis and NAFLD. We sought to review the published data on the associations between NAFLD and aortic stiffness, in order to better understand the interplay between these two conditions and identify possible common physiopathological mechanisms.

Increased aortic stiffness predicts future development and progression of peripheral neuropathy in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study.

AIMS/HYPOTHESIS: Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication that is strongly associated with poor glycaemic control and also with a worse prognosis. We aimed to evaluate the predictors of the development and progression of DPN in a cohort of high-risk patients with type 2 diabetes. METHODS: In a prospective study, 477 patients with type 2 diabetes were clinically assessed for the presence of DPN at baseline and after a median follow-up of 6.2 years (range 2-10 years). Clinical laboratory data were obtained at study entry and throughout the follow-up. Aortic stiffness was assessed by the carotid-femoral pulse wave velocity (cf-PWV) at baseline. Multivariate Poisson regression analysis was used to examine independent predictors of the development/progression of DPN. RESULTS: At baseline, 135 patients (28%) had DPN, and during follow-up 97 patients (20%) had either a new development or a worsening of DPN. Patients who showed a development or progression of DPN were taller and had a longer duration of diabetes, a greater prevalence of other microvascular complications and hypertension, greater aortic stiffness and poorer glycaemic control than patients who did not have new or progressive neuropathy. After adjustments for the baseline prevalence of DPN, the patient's age and sex, and the time interval between DPN assessments; an increased aortic stiffness (cf-PWV >10 m/s) were predictive of new/progressive DPN (incidence rate ratio 2.04, 95% CI 1.28, 3.23; p = 0.002). Other independent predictors were the mean first-year HbA1c level (p = 0.05), nephropathy (p = 0.006), arterial hypertension (p = 0.06) and height (p = 0.03). CONCLUSIONS/INTERPRETATION: Increased aortic stiffness at baseline predicts the future development or progression of peripheral neuropathy, independent of diabetic metabolic control, suggesting a physiopathological link between macrovascular and microvascular abnormalities in type 2 diabetes.

Cardiovascular and renal complications in patients with resistant hypertension.

With an increased prevalence, resistant hypertension is recognized as an entity with a high cardiovascular morbidity and mortality. In a large cohort of patients with resistant hypertension, the crude incidence rate of total cardiovascular events reached 4.32 per 100 patient-years of follow-up (19.6 %), with a cardiovascular mortality of 8.3 % (incidence rate of 1.72 per 100 patient-years). Cardiovascular event rates are significantly higher in resistant hypertensives compared with non-resistant (18.0 % versus 13.5 %). In the same way, the prevalence of established cardiovascular and renal disease, as the asymptomatic organ damage (represented by left ventricular hypertrophy, carotid wall thickening, arterial stiffness, and microalbuminuria) is higher in these patients. Many studies have demonstrated a strong association between damage to these organs with higher blood pressure levels, the diagnosis of true resistant hypertension, and refractory hypertension. All efforts should be employed in order to control blood pressure and also to regress and/or prevent subclinical cardiovascular and renal damage. The focus should be on prevention of cardiovascular and renal complications, improving the prognosis of resistant hypertension.