Long-term visit-to-visit glycemic variability as predictor of micro- and macrovascular complications in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study.

BACKGROUND: Long-term visit-to-visit glycemic variability is an additional measure of glycemic control. We aimed to evaluate the prognostic value of several measures of glycemic variability for the occurrence of micro- and macrovascular complications, and all-cause mortality in patients with type 2 diabetes. METHODS: 654 individuals were followed-up over a median of 9.3 years. Glycemic variability (SDs and coefficients of variation of HbA1c and fasting glycaemia) was measured during the first 12- and 24-months. Multivariate Cox analysis, adjusted for risk factors and mean HbA1c and fasting glycaemia levels, examined the associations between glycemic variability and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications [total cardiovascular events (CVE), major adverse CVEs (MACE) and cardiovascular mortality], and of all-cause mortality. RESULTS: During follow-up, 128 patients had a CVE (96 MACE), and 158 patients died (67 from cardiovascular diseases); 152 newly-developed or worsened diabetic retinopathy, 183 achieved the renal composite outcome (89 newly developed microalbuminuria and 91 deteriorated renal function), and 96 newly-developed or worsened peripheral neuropathy. Glycemic variability, particularly the 24-month parameters either estimated by HbA1c or by fasting glycemia, predicted all endpoints, except for retinopathy and peripheral neuropathy development/progression, and was a better predictor than mean HbA1c. Glycemic variability predicted retinopathy development/progression in patients with good glycemic control (HbA1c ≤ 7.5%, 58 mmol/mol) and predicted new-incident peripheral neuropathy. CONCLUSIONS: Long-term visit-to-visit glycemic variability is an additional and frequently a better glycemic parameter than mean HbA1c levels for assessing the risk of future development of micro- and macrovascular complications in patients with type 2 diabetes.

Initial and accrued damage as predictors of mortality in Brazilian patients with systemic lupus erythematosus: a cohort study.

The aim of this study was to investigate whether initial and accrued organ damage measured by Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) predicts mortality in cohort of Brazilian patients with systemic lupus erythematosus (SLE). One hundred and five outpatients with SLE were enrolled from July 2000 to March 2001; their demographics, disease manifestations, interventions and quantified disease activity (SLEDAI) were obtained. SDI was measured at baseline and at the end of follow-up. Initial and accrued SDI prognostic values for mortality were investigated by multivariate Cox survival analysis and Kaplan-Meyer survival curves. After a median follow-up of 6.3 years, 19 patients died due to disease activity, end-organ failure, cardiovascular events, cancer and infection. Deceased patients had longer disease duration and greater initial and final SDI than survivors had. After adjustment for age, sex and disease duration, both initial and final SDI >/= 3 points were independent predictors of mortality, with hazard ratios (HRs) of 3.0 (1.1-8.2) and 4.7 (1.6-14.5), respectively. Damage accrual during follow-up was the strongest predictor of death (HR: 5.1, 2.0-13.0). Renal and pulmonary damages were the main predictors of increased mortality risk. In conclusion, baseline and accrued damage increase mortality risk in Brazilian patients with SLE. Measures to prevent damage development and progression are urgent to reduce the mortality of patients with SLE.

Gross proteinuria is a strong risk predictor for cardiovascular mortality in Brazilian type 2 diabetic patients.

Increased proteinuria is recognized as a risk predictor for all-cause and cardiovascular mortality in diabetic patients; however, no study has evaluated these relationships in Brazilian patients. The aim of this study was to investigate the prognostic value of gross proteinuria for all-cause and cardiovascular mortalities and for cardiovascular morbidity in a cohort study of 471 type 2 diabetic individuals followed for up to 7 years. Several clinical, laboratory and electrocardiographic variables were obtained at baseline. The relative risks for all-cause, cardiovascular and cardiac mortalities and for cardiovascular and cardiac events associated with the presence of overt proteinuria (>0.5 g/24 h) were assessed by Kaplan-Meier survival curves and by multivariate Cox regression model. During a median follow-up of 57 months (range 2-84 months), 121 patients (25.7%) died, 44 from cardiovascular and 30 from cardiac causes, and 106 fatal or non-fatal cardiovascular events occurred. Gross proteinuria was an independent risk predictor of all-cause, cardiovascular and cardiac mortalities and of cardiovascular morbidity with adjusted relative risks ranging from 1.96 to 4.38 for the different endpoints. This increased risk remained significant after exclusion of patients with prior cardiovascular disease at baseline from the multivariate analysis. In conclusion, gross proteinuria was a strong predictor of all-cause, cardiovascular and cardiac mortalities and also of cardiovascular morbidity in a Brazilian cohort of type 2 diabetic patients. Intervention studies are necessary to determine whether the reduction of proteinuria can decrease morbidity and mortality of type 2 diabetes in Brazil.

Gross proteinuria is a strong risk predictor for cardiovascular mortality in Brazilian type 2 diabetic patients

Increased proteinuria is recognized as a risk predictor for all-cause and cardiovascular mortality in diabetic patients; however, no study has evaluated these relationships in Brazilian patients. The aim of this study was to investigate the prognostic value of gross proteinuria for all-cause and cardiovascular mortalities and for cardiovascular morbidity in a cohort study of 471 type 2 diabetic individuals followed for up to 7 years. Several clinical, laboratory and electrocardiographic variables were obtained at baseline. The relative risks for all-cause, cardiovascular and cardiac mortalities and for cardiovascular and cardiac events associated with the presence of overt proteinuria (>0.5 g/24 h) were assessed by Kaplan-Meier survival curves and by multivariate Cox regression model. During a median follow-up of 57 months (range 2-84 months), 121 patients (25.7 percent) died, 44 from cardiovascular and 30 from cardiac causes, and 106 fatal or non-fatal cardiovascular events occurred. Gross proteinuria was an independent risk predictor of all-cause, cardiovascular and cardiac mortalities and of cardiovascular morbidity with adjusted relative risks ranging from 1.96 to 4.38 for the different endpoints. This increased risk remained significant after exclusion of patients with prior cardiovascular disease at baseline from the multivariate analysis. In conclusion, gross proteinuria was a strong predictor of all-cause, cardiovascular and cardiac mortalities and also of cardiovascular morbidity in a Brazilian cohort of type 2 diabetic patients. Intervention studies are necessary to determine whether the reduction of proteinuria can decrease morbidity and mortality of type 2 diabetes in Brazil.

QT-interval parameters are increased in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) patients have increased cardiovascular morbidity and mortality. QT-interval parameters are presumed markers of cardiovascular risk and have not been previously evaluated in SLE. Standard 12-lead ECGs were obtained from 140 female SLE outpatients and 37 age and body mass index-matched controls. QT interval was measured in each lead and heart rate-corrected maximum QT-interval duration (QTcmax) and QT-interval dispersion (QTd) were calculated. Risk factors for cardiovascular disease and lupus clinical features, disease treatment, disease activity and damage index were recorded. SLE patients have increased QT-interval parameters when compared to controls (QTcmax: 427.91 +/- 31.53 ms(1/2) versus 410.05 +/- 15.45 ms(1/2), P < 0.001; QTd: 52.38 +/- 22.21 ms versus 37.12 +/- 12.88 ms, P < 0.001). These differences persisted after excluding those patients with arterial hypertension, diabetes and with ECG abnormalities (QTcmax: 419.90 +/- 28.78 ms(1/2) versus 409.15 +/- 15.85 ms(1/2), P = 0.041; QTd: 54.74 +/- 26.00 ms versus 37.96 +/- 13.05 ms, P = 0.001). Multivariate linear regression for factors associated with QTcmax selected the presence of electrocardiographic left ventricular hypertrophy (ECG-LVH) (P = 0.003), nonspecific ST-T-wave abnormalities (P = 0.022) and left atrial enlargement (P = 0.044). Multivariate associates with QTd were age (P = 0.018), ECG-LVH (P = 0.022) and ST-T abnormalities (P = 0.031). In conclusion, SLE patients have increased QT interval parameters when compared to controls. This prolongation may lead to an increased cardiovascular risk. This finding might be due to subclinical atherosclerotic cardiovascular disease.

Long-term thalidomide use in refractory cutaneous lesions of lupus erythematosus: a 65 series of Brazilian patients.

Thalidomide has been reported as efficacious in refractory cutaneous lupus erythematosus (LE). The most fearful side-effects are teratogenicity and neuropathy. We reported clinical efficacy of long-term low-dose use of thalidomide in 65 patients with LE, emphasizing the prevalence of adverse effects, especially of neuropathy and its related factors. Data obtained from medical records included age, sex, disease duration, and the presence of diagnostic criteria for systemic lupus erythematosus (SLE), the extent and activity of cutaneous lesions and previous treatments. Sixty-three patients (98.9%) presented complete or partial improvement with thalidomide therapy. Drowsiness occurred in 50 patients (77%). Twenty-eight patients (43.2%) presented neuropathy symptoms. Nerve conduction studies were done in 21 (75%) of them and were abnormal in 12 (57%). With the interruption of thalidomide, 24 (82.5%) had complete or partial improvement of neuropathy symptoms and 23 (82%) of them had cutaneous relapse. There were no significant differences between those who developed or not neuropathy in treatment duration, age, total dose and systemic versus cutaneous LE. In conclusion, thalidomide can be used in refractory cutaneous LE with great efficacy and relative security. Controlled studies with schemes with lower doses or intermittent usage or alternative drugs are wanted to reduce the burden of cutaneous morbidity of lupus erythematosus.

Usefulness of QT-interval parameters for cardiovascular risk stratification in type 2 diabetic patients with arterial hypertension.

QT-interval parameters are potential indicators of increased cardiovascular risk. We evaluated prospectively their prognostic value, in relation to other risk markers, for cardiovascular fatal and nonfatal events in a cohort of 271 hypertensive type 2 diabetic outpatients. QT intervals were measured from 12-lead standard ECGs obtained on admission and maximum rate-corrected QT-interval duration and QT-interval dispersion (QTd) calculated. Clinical and laboratory data and 2-D echocardiograms (available in 126 patients) were recorded. Survival analyses included Kaplan-Meier survival curves, uni and multivariate Cox proportional-hazards models. After a median follow-up of 55 months (range 2-84), 68 total fatal or nonfatal cardiovascular events and 34 cardiovascular deaths (24 of them from cardiac causes) were observed. In multivariate Cox analysis, QTd was an independent predictor for total cardiovascular events (HR: 1.16, 95% CI: 1.01-1.34, for each 10 ms increments) and for cardiac deaths (HR: 1.28, 95% CI: 1.01-1.60). Other independent risk indicators for cardiovascular morbidity and mortality were echocardiographic left ventricular hypertrophy (Echo-LVH), serum triglycerides, presence of pre-existing cardiac and peripheral arterial disease, age, diabetes duration, heart rate and the presence of frequent ventricular premature contractions on ECG. The combination of QTd and Echo-LVH improved cardiovascular risk stratification compared with either alone, the presence of both prolonged QTd (>65 ms) and Echo-LVH was associated with a 3.2-fold (95% CI: 1.7-6.1) increased risk of a first cardiovascular event and a 5.9-fold (95% CI: 2.1-16.4) increased risk of cardiovascular death. Thus, QT provided additive prognostic information for cardiovascular morbidity and mortality beyond that obtained from conventional risk markers, including Echo-LVH, in type 2 diabetic patients with arterial hypertension.

Rate, pattern and factors related to damage in Brazilian systemic lupus erythematosus patients.

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI) is an accepted instrument to ascertain damage. It has been shown to vary among different SLE populations. The aim of this study was to assess SDI score, pattern and factors related to damage in Brazilian SLE outpatients. The SDI was obtained in 105 patients with a median age of 41 (5-95%, 19-61.7) years and a median SLE duration of 127 (17.6-345.9) months. Patients had a median SDI of 2 (0-8) and 81.9% had some damage (SDI > 0). Damage was associated with a higher number of ACR criteria for SLE in multivariate analysis (OR = 2.32, 95%CI = 1.23-4.37, P = 0.009). Antiphospholipid syndrome (APS) (OR = 9.82, 95%CI = 2.74-35.23, P < 0.001), methylprednisolone pulses (OR = 3.91, 95%CI = 1.19-12.81, P = 0.024), age (OR = 1.70, 95%CI = 1.02-1.13, P = 0.011) and prednisone use duration (OR = 1.01, 95%CI = 1.002-1.02, P = 0.020) were related to severe damage (SDI > or = 4). Hypertension was associated with renal, cardiac and atherosclerotic damage, as cyclophosphamide pulses were with premature menopause. In conclusion, damage was very frequent in Brazilian SLE patients, mainly due to skin involvement, compared to other SLE populations. The presence of APS was the major independent contributor to the development of severe damage. Arterial hypertension was identified as a common risk factor for renal, cardiac and atherosclerotic damage.

Multivariate associates of QT interval parameters in diabetic patients with arterial hypertension: importance of left ventricular mass and geometric patterns.

The aim of the study was to assess the determinants of increased QT interval parameters in diabetic patients with arterial hypertension and, in particular, the strength of their relationships to echocardiographically derived left ventricular mass (LVM) and geometric patterns. In a cross-sectional study with 289 hypertensive type 2 diabetic outpatients, maximal QT and QTc (heart rate-corrected) intervals, and QT, QTc, and number-of-leads-adjusted QT interval dispersions were manually measured from standard baseline 12-lead ECGs. Electrocardiographic criteria for left ventricular hypertrophy (LVH) were either Sokolow-Lyon or Cornell sex-specific voltages. LVM and geometric patterns were determined by 2D echocardiography. Statistical analyses involved bivariate tests (Mann-Whitney, chi2, Spearman's correlation coefficients, ANOVA and receiver-operating-characteristic (ROC) curve analyses) and multivariate tests (multiple linear and logistic regressions). QT dispersion measurements showed significant correlations with echocardiographic LVM (r=0.26-0.27). ROC curves demonstrated a poor isolated predictive performance of all QT parameters for detection of LVH (areas under curve: 0.58-0.59), comparable to that of electrocardiographic voltage criteria. Only patients with concentric hypertrophy had significantly increased QT dispersion (QTd) when compared to those with normal geometries (64.24+/-21.09 vs 53.20+/-15.35, P<0.05). In multivariate analyses, both electrocardiographic and echocardiographic LVH were independent predictors of increased QTd, as well as only QTd and gender were determinants of LVM. In conclusion, increased QT interval dispersion is associated with LVM and concentric hypertrophy geometric pattern in diabetic hypertensive patients, although in isolation neither QTd nor any QT parameter presents enough predictive performance to be recommended as screening procedures for detection of LVH.