Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: We investigated effects of renal function and albuminuria on cardiovascular outcomes in 9,795 low-risk patients with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. METHODS: Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5 years. RESULTS: Lower estimated GFR (eGFR) vs eGFR ≥90 ml min⁻¹ 1.73 m⁻² was a risk factor for total CVD events: (HR [95% CI] 1.14 [1.01-1.29] for eGFR 60-89 ml min⁻¹ 1.73 m⁻²; 1.59 [1.28-1.98] for eGFR 30-59 ml min⁻¹ 1.73 m⁻²; p < 0.001; adjusted for other characteristics). Albuminuria increased CVD risk, with microalbuminuria and macroalbuminuria increasing total CVD (HR 1.25 [1.01-1.54] and 1.19 [0.76-1.85], respectively; p = 0.001 for trend) when eGFR ≥90 ml min⁻¹ 1.73 m⁻². CVD risk was further modified by renal status changes over the first 2 years. In multivariable analysis, 77% of the effect of eGFR and 81% of the effect of albumin:creatinine ratio were accounted for by other variables, principally low HDL-cholesterol and elevated blood pressure. CONCLUSIONS/INTERPRETATION: Reduced eGFR and albuminuria are independent risk factors for cardiovascular events and mortality rates in a low-risk population of mainly European ancestry. While their independent contributions to CVD risk appear small when other risk factors are considered, they remain excellent surrogate markers in clinical practice because they capture risk related to a number of other characteristics. Therefore, both should be considered when assessing prognosis and treatment strategies in patients with diabetes, and both should be included in risk models.

Computation of ventilation-perfusion ratio with Kr-81m in pulmonary embolism.

Diagnostic difficulties occur in pulmonary embolism (PE) during visual analysis of ventilation-perfusion images in matched defects or in chronic obstructive lung disease (COPD). In 44 patients with angiographically confirmed PE and in 40 patients with COPD, the regional ventilation-perfusion ratios (V/Q) were therefore computed using krypton-81m for each perfusion defect, and were displayed in a functional image. In patients with PE and mismatched defects, a high V/Q (1.96) was observed. A V/Q greater than 1.25 was also found in nine of 11 patients having PE and indeterminate studies (studies with perfusion abnormalities matched by radiographic abnormalities). COPD was characterized by matched defects and low V/Q. The percentage of patients correctly classified as having PE or COPD increased from 56% when considering the match or mismatched character to 88% when based on a V/Q of 1.25 in the region of the perfusion defect. This quantitative analysis, therefore, seems useful in classifying patients with scintigraphic suspicion of PE.

Peripheral action of spironolactone: improvement in arterial elasticity.

Arterial elasticity, which can be assessed by means of a piezogram, is thought to be involved in the development of hypertension. In hypertensive patients (and with aging in normal subjects), arterial elasticity is reduced. Long-term administration of spironolactone, beta blockers, or a beta-blocker/dihydralazine combination to hypertensive patients sufficiently reduced systolic and diastolic blood pressure to about the same extent; however, only spironolactone had any effect on piezoelectric indexes of arterial elasticity.

Total respiratory pressure-volume curves in the adult respiratory distress syndrome.

To assess the value of measuring compliance in the adult respiratory distress syndrome, sequential pressure-volume curves were obtained in 19 patients with this syndrome. Analysis of the pressure-volume curves allowed separation of the patients into the following four groups: (1) group 1 (n = 6), normal compliance measured during deflation, little hysteresis, and no inflection in the ascending limb of the pressure-volume tracing; (2) group 2 (n = 8), normal compliance during deflation, increased hysteresis, and presence of an inflection; (3) group 3 (n = 10), decreased compliance during deflation, marked hysteresis, and presence of an inflection; and (4) group 4 (n = 10), reduced compliance during deflation, no increased hysteresis, and no inflection. These patterns were correlated with the stage of the adult respiratory distress syndrome and to the pattern of the chest x-ray film. Group 2 corresponds to the initial stage of the syndrome and to pure alveolar opacities on the chest x-ray film. Group 3 is seen later in the course of the syndrome and corresponds to mixed alveolar and interstitial opacities. Group 4 corresponds to patients with end-stage adult respiratory distress syndrome (two weeks) and a predominant interstitial pattern on the chest x-ray film. Group 1 corresponds to a nearly normal chest x-ray film and to recovery.

Decreased plasma epinephrine concentrations after glucose ingestion in humans.

Plasma levels of norepinephrine (NE), epinephrine (E), immunoreactive insulin (IRI), and glucose were measured in six healthy volunteers after glucose consumption and in six volunteers after a water solution. Ingestion of the glucose (100 g) solution significantly decreased E levels from 46.7 +/- 8.0 to 20.8 +/- 1.9 pg/mL (P less than 0.01). Three hours after the glucose ingestion, plasma E levels nearly returned to basal values. Plasma IRI and glucose levels peaked at 45 minutes after glucose consumption (P less than 0.01), then declined toward basal values. Plasma NE levels were unaffected by glucose consumption. There were no changes in glucose, IRI, NE, or E levels in the control group. These results suggest that E behaves as a counter-regulatory hormone to insulin under stimulation by glucose.

[Phagocytic activity of monocytes in human primary glomerulonephritis]. / Activité phagocytaire des monocytes dans les glomérulonéphrites primitives humaines.

Circulating immune complexes (CIC) account for a majority of GN. Their pathogenicity depends on size, molecular composition, glomerular hemodynamics and activity of phagocytes. The phagocytic function of peripheral monocytes was studied in 23 patients with nonsystemic GN. Phagocytic activity of peripheral blood monocytes was assessed in vitro, by calculating phagocytic index (IP: number of zymozan particles in each monocyte) and phagocytosis percentage (PP: number of phagocyting monocytes); the tests were carried out on autologous and heterologous serum samples. In 13 controls, PP was 79 +/- 5.8%. In 7 membranous GN, 6 membranoproliferative GN and 10 lipoid nephrosis, PP was severely decreased, 63.4 +/- 9.6%, 52.1 +/- 19% and 52.2 +/- 14%. In each group of GN, these results were significantly different from controls (p less than 0.01). In all groups these results were similar in autologous and heterologous serum samples (55 +/- 13% and 57.5 +/- 16%; NS). Therefore, this defect was not linked to the presence of serum inhibitors. In conclusion, alterations of phagocytic activity is present in some primary GN and may explain an insufficient rate of CIC removal.

[Idiopathic nephrotic syndrome and the HLA allele. Prevalence of age-related DR7]. / Syndrome néphrotique idiopathique et allèle HLA. Prévalence de DR7 liée à l'âge.

High prevalence of HLA DR7 was well documented in idiopathic nephrotic syndrome (INS) of childhood. Our data in 43 INS, child and adult patients, did not show any significant difference from control group, specially for HLA DR7. Moreover a significant difference occurred when the data was compared in child and adult INS patients. HLA DR7 was more frequent when the nephrotic syndrome appeared before 15 years old. There was no correlation between the presence of HLA DR7 and those of allergy history or increased serum IgE level, on the opposite with previous data. The presence of DR7 would favor its onset at an earlier age. Alternatively, the difference in DR7 prevalence could be an additional argument for considering that the corticosensitivity and negative histological criteria might collect, under the same name, different glomerulopathies.

[Treatment of arterial hypertension. Efficacy of nitrendipine 20 mg/day]. / Traitement de l'hypertension artérielle. Efficacité de la nitrendipine 20 mg/j.

The effectiveness and acceptability of nitrendipine, given as a single 20 mg tablet in the morning, were evaluated in general practice in 6.058 hypertensive patients. Visits were planned after 2, 6 and 12 weeks of treatment. Eighty-nine percent completed the 12-week study, 95 percent of them receiving 20 mg of nitrendipine once daily. Adverse events were observed in 26 percent of the patients, mainly during the first two weeks, when flushing and peripheral edema occurred in 9 and 7 percent of the patients respectively. Both led to withdrawal of 4 percent of the patients included over 3 months. A supine diastolic blood pressure below 90 mmHg was achieved in 65 percent of the patients, irrespective of age, sex, activity, smoking habits, and presence of diabetes or previous antihypertensive therapy. This large-scale study further established the effectiveness of nitrendipine as monotherapy given once daily in most hypertensive patients. Eight out of 10 patients felt they had benefited from the treatment. The investigators were satisfied with the results in 66 percent of the patients. They considered that the main advantage of nitrendipine was ease of use.

[Therapeutic importance and tolerance of coated 50 mg Vectarion tablets (almitrine bismesylate) at a dosage of 100 mg/day. Study of blood gas, clinical and biological results after a year of long-term treatment]. / Intérêt thérapeutique et acceptabilité du Vectarion 50 mg comprimés enrobés (bismésilate d'almitrine) à la dose de 100 mg/jour. Etude des résultats gazométriques, cliniques et biologiques en traitement prolongé pendant 1 an.

The objectives of this study, in which Almitrine bismesylate was administered for one year in chronic bronchitics with obstructive hypoxia, were to assess its clinical and gasometric efficacy and its clinical, laboratory, spirometric and electrocardiac acceptability. The blood gas results show a significant rise in PaO2 (p less than 0.001) rising by 5.5 mmHg after 6 months (T6) and by 6.0 mmHg after 12 months (T12) in comparison with the value at the study's onset. The PaCO2 fell by 3.3 mmHg at T6 and 2.7 mmHg at T12 (p less than 0.001). The dyspnoea of the patient, scored by the doctor on a scale of severity from 0 to 5 was situated on a mean of 3.3 points at the beginning of the study. It was significantly reduced by 0.8 points at T6 and by 0.9 points at T12 (p less than 0.001). The percentage of patients hospitalised during the course of the study fell significantly in comparison with the previous year, from 68% to 49% (p less than 0.001). The improvement in clinical status and in blood gases bore no relation to changes in respiratory function. The clinical acceptability of the product was good; few side effects were observed and the respiratory, digestive and neurological problems were often pre-existing. They only led to cessation of treatment in three cases. The electrocardiogram was unchanged. The laboratory investigations was unchanged, with the exception of a fall in red blood cells in relation to the correction of the hypoxaemia in polycythaemic patients.

Fibrates and microvascular complications in diabetes--insight from the FIELD study.

Fibrates are widely prescribed lipid-lowering drug in the treatment of dyslipidemia. Their main clinical effects, mediated by peroxisome proliferative activated receptor (PPAR) alpha activation, are a moderate reduction in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, a marked reduction in triglycerides (TG) and an increase in high-density lipoprotein cholesterol (HDL-C), usually dependent of their baseline levels and dyslipidemia type. A beneficial effect on cardiovascular outcomes but also on inflammatory and thrombogenesis pathways as well as antioxidant properties have been evidenced conferring other pleiotropic effects to fibrates. Diabetic retinopathy, nephropathy and neuropathy are the major microvascular complications of Type 2 diabetes mellitus (T2DM) and their presence can accentuate the risk of cardiovascular disease. Hyperglycemia, hypertension, genetic susceptibility among other risk factors play a significant role in the development and progression of these complications. Plasma lipid abnormalities are also involved in the pathogenesis of microvascular diseases suggesting a potential benefit of lipid lowering drugs in their prevention. Clofibrate was the first fibrate in the 60's to show an improvement in the retinal hard exudation in subjects with diabetic retinopathy. Recently, in the Fenofibrate Intervention in Event Lowering in Diabetes (FIELD) study fenofibrate treatment demonstrated a significant 30% reduction in the need for laser therapy in patients with and without known diabetic retinopathy, and more particularly in the first course of laser treatment for both macular edema and proliferative retinopathy. In addition, fenofibrate treatment was associated with less albuminuria progression and reduced risk of non traumatic distal amputations. These results, along with previous evidence of positive effects on microvascular complications, suggest that fibrates, and particularly fenofibrate, offer good opportunity to prevent the most serious complications of diabetes.

A one-year double-blind placebo-controlled study of the efficacy and safety of almitrine bismesylate in hypoxic COLD patients. Monitoring progress status on 490 patients entered into the VIMS study before January 1st, 1984.

The aim of the VIMS group is to verify the efficacy and acceptability of almitrine bismesylate (ABM) taken orally in the treatment of chronic obstructive bronchitis, by an international long-term study, one year controlled against placebo. This study includes more than 800 out-patients in 70 centres in 12 countries. 490 patients entered the study before 1/1/84, after the first 9 months of the inclusion period. 60% of patients are treated in France, 20% in the U.K. and Ireland and 20% in Belgium, Denmark, Italy, Switzerland. Their mean FEV1 is 0.87 liters, their mean PaO2 is 57 mmHg. The study protocol foresees two control visits separated by a 3 week interval before entry into the study in order to verify the stability of the patients on the basis of clinical, spirometric and gazometric data; the variation in PaO2 is less than or equal to 6 mmHg in more than 90% of the patients. The severity of the disease is assessed by the existence of an hospitalisation during the year preceeding the study in 55% of the patients, the necessity of oxygenotherapy at home for at least 12hr/day in 1/3 of them. The treatment of the latter was attributed separately at random to seek in a prospective manner the interest of associating O2 and ABM. During the study, the mortality of the patients included is 6% and about 70% of the patients completed the study period. The survey of adverse reactions and reasons for treatment interruption is progressively established by close collaboration between the investigators and monitors, to comply with the directives of pharmacosurveillance for severe and polymedicated patients. The analysis of the results to be carried out at the end of the study after verification and correction by the investigators, should enable us to enhance our knowledge of the clinical and gazometric parameters in patients with chronic obstructive disease followed for one year and treated by conventional means (control group) and the activity of ABM in order to confirm its therapeutic value in the treatment of chronic obstructive bronchitis.

Effectiveness of nitrendipine, 20 mg once daily in the management of hypertension in general practice.

The effectiveness of nitrendipine, given as a single 20 mg tablet in the morning, was evaluated in general practice in 6,058 hypertensive patients. They filled in a questionnaire on their activities and previous antihypertensive treatment, if any. Visits were planned after 2, 6, and 12 weeks. Then, patients and general practitioners gave their assessment of the treatment. Eighty-four percent completed the 12-week study while receiving 20 mg of nitrendipine once daily. Adverse events were observed in 26% of the patients, mainly during the first 2 weeks, where flushing and peripheral edema occurred in 9 and 7% of the patients, respectively. Both led to withdrawal of 4% of the included patients over 3 months. A supine diastolic blood pressure below 90 mm Hg was achieved in 65% of the patients, irrespective of age, sex, activity, smoking habits, and presence of diabetes or previous antihypertensive therapy. In conclusion, this large-scale study further established the effectiveness of nitrendipine as monotherapy given once daily in most hypertensive patients. Eight patients in 10 felt they had benefited from the treatment. The investigators were satisfied with the results in 66% of the patients. They considered that the main advantage of nitrendipine was ease of use.

Almitrine bismesylate: a long-term placebo-controlled double-blind study in COAD--Vectarion International Multicentre Study Group.

701 patients, age 61.9 +/- 8.3 yr (mean +/- SD), with hypoxaemic chronic obstructive airways disease (COAD) were entered into a one yr placebo-controlled double-blind study to determine the effect of oral almitrine bismesylate on arterial blood gas tensions and clinical condition. Initial arterial O2 tension (PaO2) was 7.6 +/- 0.8 kPa (57.0 +/- 6.2 mmHg) and arterial CO2 tension (PaCO2) was 6.0 +/- 0.9 kPa (45.2 +/- 6.7 mmHg). Forced expiratory volume in one second (FEV1) was 0.87 +/- 0.35 l and forced vital capacity (FVC) was 2.31 +/- 0.72 l. 163 patients, evenly distributed between treated and untreated groups, were receiving long-term O2 therapy; other conventional therapy was continued. In a stabilization period before treatment, excellent reproducibility of blood gas tensions and spirometry was achieved. In the placebo group (P; n = 357), little change in physiological measurements or clinical assessment was recorded, 90 patients (25%) were lost from the study, mostly due to deterioration of their respiratory disease or to death; 3.4% withdrew for adverse reactions. The almitrine group (A; n = 344), received 100-200 mg per day orally in two divided doses, depending on the improvement in PaO2 achieved. On entry to the study their blood gas tensions, lung function tests, clinical assessment, history of hospitalization and frequency of right heart failure were not significantly different from the placebo group. After one yr of treatment, PaO2 rose from 7.6 +/- 0.8 kPa (57.4 +/- 6.1 mmHg) to 8.5 +/- 1.3 kPa (63.7 +/- 9.7 mmHg), p less than 0.001 compared with the placebo group. Red cell count decreased p less than 0.001 compared with the placebo group and FEV1 increased from 0.92 l to 0.95 l, p less than 0.001 compared with the placebo group. Dyspnoea, assessed on a 100 mm analog scale was unchanged in the almitrine group as a whole, but some individual patients withdrew on account of breathlessness. A smaller proportion of patients in group A were hospitalized and had episodes of right heart failure during the study than in group P (p less than 0.05). Vital signs, biochemistry and ECG characteristics did not change. 139 patients (40%) in this group did not complete the study, 35 (10%) through deterioration of respiratory symptoms or death (4.9%); 43 (12.5%) withdrew because of adverse reactions, either drug-related or not. The most frequent adverse reactions were gastro-intestinal, central nervous system disturbances, increased dyspnoea and peripheral paraesthesiae.(ABSTRACT TRUNCATED AT 400 WORDS)