Diabetic retinopathy is associated with an increased incidence of cardiovascular events in Type 2 diabetic patients.

AIMS: We investigated the association of diabetic retinopathy with the risk of incident cardiovascular disease (CVD) events in a large cohort of Type 2 diabetic adults. METHODS: Our study cohort comprised 2103 Type 2 diabetic outpatients who were free of diagnosed CVD at baseline. Retinal findings were classified based on fundoscopy (by a single ophthalmologist) to categories of no retinopathy, non-proliferative retinopathy and proliferative/laser-treated retinopathy. Outcomes measures were incident CVD events (i.e. non-fatal myocardial infarction, non-fatal ischaemic stroke, coronary revascularization procedures or cardiovascular death). RESULTS: During approximately 7 years of follow-up, 406 participants subsequently developed incident CVD events, whereas 1697 participants remained free of diagnosed CVD. After adjustment for age, body mass index, waist circumference, smoking, lipids, glycated haemoglobin, diabetes duration and medications use, patients with non-proliferative or proliferative/laser-treated retinopathy had a greater risk (P < 0.001 for all) of incident CVD events than those without retinopathy [hazard ratio 1.61 (95% confidence interval 1.2-2.6) and 3.75 (2.0-7.4) for men, and 1.67 (1.3-2.8) and 3.81 (2.2-7.3) for women, respectively]. After additional adjustment for hypertension and advanced nephropathy (defined as overt proteinuria and/or estimated glomerular filtration rate < or = 60 ml/min/1.73 m(2)), the risk of incident CVD remained markedly increased in those with proliferative/laser-treated retinopathy [hazard ratio 2.08 (1.02-3.7) for men and 2.41 (1.05-3.9) for women], but not in those with non-proliferative retinopathy. CONCLUSIONS: Diabetic retinopathy (especially in its more advanced stages) is associated with an increased CVD incidence independent of other known cardiovascular risk factors.

[Chikungunya arthritis: report of 6 cases]. / Artropatia da Chikungunya: descrizione di 6 casi.

Chikungunya is an arboviral disease transmitted by Aedes mosquitoes. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia, that can persist for months. Chikungunya virus, a member of the genus Alphavirus, has recently caused a large outbreak on islands in the Indian Ocean and on the Indian subcontinent. The ongoing outbreak has involved more than 1.5 million patients, including travellers who have visited these areas. We describe our casistic of six travellers with Chikungunya arthropathy. All patients experienced fever and rash of short term during a travel in areas of epidemicity. All patients had peripheral poliarthralgias, which duration was >2 months in 4 cases (66%) and >6 months in 1 case (16%).

ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans.

The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Delta approximately 26%) of endothelium-dependent vasodilation in the femoral artery (P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirculation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.

Noninvasive detection of functional alterations of the arterial wall in IDDM patients with and without microalbuminuria.

OBJECTIVE: To test endothelial function in a group of 10 normoalbuminuric and eight microalbuminuric insulin-dependent diabetes mellitus patients (ages 28 +/- 3 [mean +/- SE] and 28 +/- 1 years, respectively), in comparison with 16 control subjects (age 35 +/- 2 years, normal subjects vs. diabetic subjects P = NS), to identify prestructural abnormalities of the arterial wall. An early stage of vascular involvement seems in fact to be characterized by functional alterations of endothelial control on vascular tone and wall interaction with circulating cells. Furthermore, many recent studies suggest the importance of microalbuminuria as an early marker not only of nephropathy but also of retinopathy and macroangiopathy. RESEARCH DESIGN AND METHODS: Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation (induced by glyceryl trinitrate administration) were evaluated in the right common femoral artery by echo-Doppler ultrasound. Arterial wall distensibility was evaluated at the common femoral artery by an echo-tracking system. RESULTS: In spite of a comparable increase in flow velocity, endothelium-mediated vasodilation was significantly reduced in diabetic subjects, particularly in microalbuminuric patients. Endothelium-independent vasodilation was also significantly impaired in diabetic subjects, particularly in microalbuminuric subjects; whereas arterial wall distensibility, an index of the viscoelastic properties of the wall, was similar in the three groups. CONCLUSIONS: These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.

ACE inhibitors improve endothelial function in type 1 diabetic patients with normal arterial pressure and microalbuminuria.

OBJECTIVE: The purpose of this study was to test whether a short-course treatment with ACE inhibitors may restore endothelium-dependent and/or -independent vasodilation in the femoral artery of microalbuminuric patients with type 1 diabetes and normal arterial pressure. RESEARCH DESIGN AND METHODS: We studied nine normotensive microalbuminuric type 1 diabetic patients and two groups of control subjects matched for femoral artery diameter to type 1 diabetic patients after placebo (control group A, n = 17) and ACE inhibitor (control group B, n = 18) treatment, respectively. The patients were enrolled in a double-blind cross-over study with a 1-week trial of either placebo, captopril (25 mg t.i.d.), or enalapril (10 mg/day) in randomized order to ascertain whether short-term ACE inhibition obtained with (captopril) or without (enalapril) a sulfhydryl donor molecule ameliorates vessel wall function. Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation were evaluated in the right common femoral artery by echo Doppler. RESULTS: Both captopril and enalapril normalized (control group B 22.9+/-3.2% per 8 min) endothelium-dependent response (19.6+/-7.5 and 18.0+/-5.3 vs. -10.4+/-4.1% per 8 min, P < 0.01, for both captopril and enalapril versus placebo, respectively) in the type 1 diabetic patients. Captopril (28.4+/-3.5 vs. 17.1+/-3.5% per 5 min during placebo, P < 0.05) but not enalapril (20.1+/-3.0 vs. 31.7+/-2.8% per 5 min, P < 0.05 for enalapril versus control group B, and NS for captopril vs. control group B) ameliorated endothelium-independent vasodilation in type 1 diabetic patients. CONCLUSIONS: ACE inhibition improves endothelium-dependent vasodilation in the femoral artery of normotensive microalbuminuric type 1 diabetic patients. Captopril also ameliorates endothelium-independent vasodilation, possibly through its sulfhydryl donor properties. These results may be of pathophysiological relevance to prevent cardiovascular complications in these patients.

Non-invasive detection of early endothelial dysfunction in hypercholesterolaemic subjects.

Hypercholesterolaemia is associated with accelerated atherogenesis. Before the evidence of morphological lesions or plaques, endothelial dysfunctions, such as impairment in endothelium-dependent vascular tone regulation, may occur. We studied 32 subjects, 16 with primary hypercholesterolaemia and 16 normocholesterolaemic controls. Flow-dependent vasodilation, an endothelium-dependent phenomenon, was evaluated by measuring femoral artery diameter and flow velocity in basal conditions and during distal post-ischemic hyperaemia, using a high resolution echo-Doppler. Arterial distensibility and compliance were evaluated for the common carotid and femoral arteries, using a pulsed echo-tracking system and measuring the absolute and relative stroke change in arterial diameter. In the hypercholesterolaemic group there was no flow-dependent arterial relaxation, indicated by the area under the curve of percentage diameter variation as a function of time. This parameter was inversely correlated with both total and LDL-cholesterol values in all population subjects. No difference was observed between the two groups in endothelium-independent vasodilation induced by glyceryl trinitrate administration or arterial wall distensibility and compliance, confirming the hypothesis of a functional defect.

Stiffness of the common carotid artery in treated hypertensive patients.

Antihypertensive treatment, by lowering blood pressure and correcting functional and/or structural abnormalities of the arterial wall, may prevent the arterial damage due to the accelerated ageing process. The objective of the present study was to determine, using a cross-sectional approach, whether arterial distensibility of patients whose blood pressure had been normalized for several months by antihypertensive treatment, was significantly higher than that of untreated hypertensive patients. The properties of the vessel wall of the common carotid artery (CCA) were studied non-invasively, using an original pulsed ultrasound echo-tracking system based on Doppler shift, during a study comparing 46 normotensive subjects and 81 age-matched hypertensive patients. The latter group included 25 patients well controlled by antihypertensive treatment for at least 3 months and 56 untreated hypertensives. The three groups did not differ with respect to age, total and high-density lipoprotein cholesterol, blood glucose and smoking. In each group, there were significant relationships between age and CCA dimensional and functional data, including end-diastolic diameter, absolute and relative stroke changes in diameter and Peterson modulus, indicating a widening of the CCA with advancing age and a decrease in its buffering function. When compared with untreated hypertensives, well controlled hypertensives had significantly lower blood pressure and Peterson elastic modulus according to age. However, although blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, their arterial distensibility remained altered compared with that of normotensive subjects (significant increase in Peterson elastic modulus). These results suggest that long-term antihypertensive treatment may not fully reverse arterial lesions due to the hypertensive disease.

Non-invasive ventilatory approach to treatment of acute respiratory failure in neuromuscular disorders. A comparison with endotracheal intubation.

OBJECTIVE: Prospectively to investigate the efficacy of non-invasive positive pressure ventilation (NPPV) combined with cricothyroid "mini-tracheostomy" (CM) as a first-line intervention in patients with acute respiratory failure (ARF) of neuromuscular origin, in comparison with positive pressure ventilation (PPV) via endotracheal intubation (ETI). DESIGN: Prospective analysis of the short-term outcomes of 14 non-consecutive patients suffering from ARF of neuromuscular origin who were administered NPPV and comparison with the outcomes of 14 matched historical control patients receiving conventional mechanical ventilation (MV) via ETI. SETTING: Adult five-bedded respiratory intensive care unit in a university hospital. PATIENTS AND INTERVENTIONS: Fourteen neuromyopathic patients who developed hypercapnic ARF and were submitted to NPPV (group A) and fourteen matched historical control patients, who were administered PPV via ETI (group B). Seven subjects receiving NPPV also underwent CM. OUTCOME MEASURES: Mortality during ICU stay and treatment failure were evaluated; treatment failure was defined as death or the need for ETI for the NPPV group and as death or the inability to wean from MV for the control group. Length of stay in the ICU and time to improvement, defined as the time required for a significant relief of dyspnea and neurologic impairment and for correction of arterial blood gases, were also compared. RESULTS: Intra-hospital mortality and treatment failure were lower in the NPPV group than in the conventional PPV via ETI group (2 vs 8 cases and 4 vs 11 cases, respectively). In addition, the duration of ICU stay for subjects who underwent NPPV was shorter than for patients who were intubated (13.6 +/- 9.7 vs 47.1 +/- 51.9 days). "Mini-tracheostomy" was well tolerated and no significant side effects were encountered. Two patient were excluded from the study because they showed a severe inability to swallow and needed to be intubated to protect the upper airway from the risk of aspiration. CONCLUSIONS: Non-invasive positive pressure ventilation in combination with CM may be considered as a safer and more effective alternative to ETI in the treatment of patients with neuromuscular disorders (NMD) who develop ARF and require MV; nevertheless, patient selection remains important, since a significant proportion of neuromyopathic patients might have to be excluded from NPPV because of severe risk of aspiration.

Evolution of carotid atheromatous lesions in endarterectomized patients.

A noninvasive follow-up using duplex ultrasonography was conducted in 128 patients who had undergone carotid endarterectomy from January 1987 to December 1988. Repeated scans of the operated area revealed a distinct increase in thickened ultrasonographic features (32% vs 8%), and a stenosing lesion was detected in 8 patients. There was also a parallel increase in the number of subjects with thicknesses of the intima adjacent to the endarterectomy area exceeding 2.5 mm. In 7% of cases, dilatation was detected in the operated area and in 27% the margin of the area was raised. The study also dealt with the contralateral carotid artery, where a progression of atheromatous involvement was observed with an increased number of cases of hemodynamically significant stenosis and 3 cases of occlusion. Periodic duplex ultrasonography in endarterectomized patients proves useful for the early detection of hemodynamically significant stenoses or of structural features potentially capable of generating emboli.

Elevated plasma fibrinogen levels in patients with essential hypertension are related to vascular complications.

AIM: We investigated whether or not fibrinogen is related to the cardiovascular risk profile and complications in hypertensive subjects. METHODS: Plasma fibrinogen and laboratory tests including factor VII, homocysteine and microalbuminuria were evaluated in 127 consecutive hypertensive subjects stratified according to cardiovascular risk. Parameters were age, gender, smoking, cholesterol, diabetes, target organ damage: left ventricular hypertrophy (LVH), carotid atherosclerotic complications and retinical vessels. RESULTS: Fibrinogen levels were significantly different between patients according to risk levels (low 290+/-73, n=20, high 342+/-94 mg/dl, n=39, very high risk 350+/-72, n=29, p=0.01), hypertension grade (II-III) and organ damage. Fibrinogen was significantly higher in patients with more severe carotid atherosclerotic lesions and vascular retinal lesions (grades II-III vs 0 and I). Also in patients, matched for age and sex, without and with carotid atherosclerotic lesions, fibrinogen was significantly higher in the latter group. No significant differences were found on the basis of IVS, creatinine and microalbuminuria. In hypertensive patients, fibrinogen directly correlated with age, by multiple linear regression. In hypertensive patients with diabetes, fibrinogen was significantly higher (466+/-176 mg/dL, n=14) than in those hypertensive without diabetes (333+/-87 mg/dL, n=113, p=0.001) and in all patients there was a a significant correlation (r=0.474, p<0.001) between blood glucose and fibrinogen. CONCLUSION: Hyperfibrinogenemia is a marker of vascular damage and could be an important factor contributing to the evolution of the complications.

[Study of flow-dependent vasodilation of the femoral artery in hypertensive and normal subjects]. / Etude de la vasodilatation flux-dépendante au niveau de l'artère fémorale chez l'hypertendu et le normotendu.

Flow dependent vasodilation of brachial artery is not significantly different in hypertensives as compared to normotensives. Since, in vitro, changes in vasomotor tone of large arteries in response to endothelial stimulation may differ depending on the territory, we re-examined phenomenon of flow-dependent vasodilation at the level of the femoral artery in 10 normotensives (NT) and 12 age matched (45 +/- 9 vs 43 +/- 4 yrs) hypertensives (HT). Systolo-diastolic variations of femoral artery diameter (D) were recorded using an original echo-tracking system based on doppler shift while blood flow velocity was measured at the same level using a bidimensional pulsed doppler system (V). A 10 min period of leg ischemia did not induce any significant change in D and V in each group but decreased foot skin blood flow (laser doppler). This decrease occurred to the same extent in NT and HT. During reactive hyperemia following release of the pneumatic cuff, V increased (from 2.1 +/- 0.3 to 12.5 +/- 2.4 cm/s in NT) and returned to control level at the 3rd min. Diastolic diameter (Dd) increased (max: 2nd min) in NT (9.3 +/- 0.8 vs 8.8 +/- 0.9 mm; p less than 0.001) and in HT (9.5 +/- 1.2 vs 8.4 +/- 1.2 mm; p less than 0.01). Dd increased to a greater extent in HT than in NT while reactive hyperemia (laser doppler) did not differ. Thus, a non-invasive method is able to demonstrate a flow-dependent vasodilation at the level of the femoral artery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Visco-elastic properties of common carotid artery in treated hypertension]. / Propriétés visco-élastiques de la carotide primitive. L'hypertendu traité.

It is now possible to measure clinically by a non-invasive method systolo-diastolic variations of the internal diameter of large arteries over 4 to 10 cardiac cycles with an original vascular echo-tracking device using Doppler shift. By the means of a transversal study of healthy subjects and patients followed up in the hypertension clinique, the authors set out to determine whether long-term non-specific antihypertensive treatment could, by correcting the blood pressure, also normalise the vascular changes encountered in hypertension. This study compared 46 normotensive subjects (Group I), 25 essential hypertensive patients with normal blood pressure recordings after at least 3 months' treatment (Group II) and 56 untreated essential hypertensive patients of the same average age (range 24 to 78 years). The common carotid artery was chosen for study of its geometry (internal diastolic diameter: Dd) and function (relative systolic expansion Ds-Dd/Dd; Perterson's elastic modulus; cross sectional compliance). The arterial diameter increased significantly with age in all three patients groups. In patients under 60 years of age, the diameter, corrected for age and sex, was significantly greater in Group II than in Group I, and similar in Groups II and III. This suggests that in spite of correcting blood pressure by long-term therapy (4.1 +/- 4.1 years), the internal diameter of a large artery such as the common carotid artery remains increased, which is in favour of the persistence of structural arterial changes rather than a prolonged vasodilator effect of the antihypertensive agents used.(ABSTRACT TRUNCATED AT 250 WORDS)

Large and small forearm arteries of essential hypertensives are less reactive to angiotensin II than to noradrenaline.

In order to investigate the reactivity to angiotensin II (Ang II) in large and small arteries in situ, brachial artery diameter, blood flow velocity, local volumic blood flow and local vascular resistance (mean arterial pressure divided by local blood flow) were determined non-invasively, using a pulsed Doppler system. Increasing doses of Ang II (0.5, 1.0 and 2.0 ng/kg per min) were given intravenously and double-blind to nine normotensive subjects (group I) and 10 hypertensive patients (group III); placebo (glucose) was given to nine hypertensives (group II). Angiotensin II did not change the brachial artery diameter, blood flow velocity, local blood flow or local resistance. Mean arterial pressure was increased slightly but significantly (P less than 0.05) by Ang II at 2 ng/kg per min in groups I and III. In contrast, we had shown previously, following the same procedure, that subthreshold doses (for the increase in mean arterial pressure) of noradrenaline reduced branchial artery diameter, velocity and local blood flow and increased local resistance in hypertensives. These results indicate that in hypertensives the vascular reactivity of the brachial circulation (1) is lower than that of other territories in response to Ang II and (2) is lower in response to Ang II than in response to noradrenaline.

Haemodynamic parameters in hypertensive patients: changes induced by lacidipine and nifedipine.

We conducted a randomly allocated, double-blind study in 16 essential hypertensive patients, eight of whom were treated with nifedipine and eight with lacidipine. The antihypertensive efficacy was evaluated and any modifications to peripheral haemodynamic parameters were observed in the brachial artery by a mechanographic method and B-mode scanner with a 10-MHz probe. Statistically significant reductions in blood pressure from basal values were observed after 1 and 6 months' treatment. Enhanced compliance (P less than 0.005), reduced characteristic impedance (P less than 0.001) and lower peripheral resistances (P less than 0.01) were also noted. Variations in pulse wave velocity and mean blood pressure showed a statistically significant correlation as early as the first month of treatment (P less than 0.01). Our results suggest that therapy with nifedipine and lacidipine allows an improvement in peripheral haemodynamics in hypertensive patients. This response is maintained in chronic treatment, even just before the next dose administration at the end of the longest dose interval.