Presence Of Microvascular Disease Research Articles

Enfermedad arterial periférica oculta en población diabética seguida en atención primaria

Introduction The aim of our study was to estimate the prevalence and associated factors of occult peripheral arterial disease (PAD) assessed by the ankle-brachial index (ABI) in subjects with type 2 diabetes mellitus followed up in a single urban Primary Care Center. Methods This is a cross-sectional study involving subjects who were sampled randomly from patients with type 2 diabetes and aged 50 to 80 years-old. The dependent variable was the presence of PAD, assessed by an ABI below 0.9. Demographic, clinical and laboratory parameters were also recorded. A forward, stepwise, logistic binary regression was built in order to examine variables associated with abnormal ABI. Results Four-hundred and fifty-six patients were included; they were 61±6 years-old, of which 243 (53%) were men. An ABI<0.9 was found in 126 patients (27.6%), 310 (68%) patients had an ABI 0.9–1.3 and only 20 patients (4.4%) had and ABI higher than 1.3. Using multivariate analyses, past or present smoking, duration of diabetes, platelet count and hypertriglyceridemia, were independently associated to PAD; on the contrary, only waist cincumference and the presence of microvascular disease were associated to an ABI higher than 1.3. Conclusion The prevalence of PAD was high and consistent with the literature, thus reinforcing the measurement of ABI for all patients with type 2 diabetes followed up in primary care. Smoking, duration of diabetes, platelet count and hypertriglyceridemia were independently associated to a low ABI.

Retinal arteriolar narrowing increases the likelihood of chronic kidney disease in hypertension

Retinal arteriolar narrowing is a marker of chronic microvascular damage from hypertension. We hypothesized that the presence of retinal arteriolar narrowing increases the likelihood of chronic kidney disease (CKD) associated with hypertension. We examined 3602 persons of Chinese, Malay and Indian ethnicities, aged at least 24 years residing in Singapore. CKD was defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m(2). Hypertension was defined as SBP of at least 140 mmHg or DBP of at least 90 mmHg or self-reported physician-diagnosed hypertension. Retinal arteriolar caliber was measured from retinal photographs and summarized. The lowest arteriolar caliber quartile was defined as retinal arteriolar narrowing. Both hypertension and retinal arteriolar narrowing were associated with CKD (n = 185), independent of major confounders, with multivariable odds ratio of 2.10 (95% confidence interval 1.46-3.02) for CKD associated with hypertension and odds ratio of 1.68 (95% confidence interval 1.04-2.71) for retinal arteriolar narrowing. The association between hypertension and CKD was stronger in the presence of retinal arteriolar narrowing (P for interaction 0.09), and joint exposure to both hypertension and retinal arteriolar narrowing was associated with a three-fold odds of having CKD (multivariable odds ratio 3.61, 95% confidence interval 1.88-6.93) compared with absence of hypertension and arteriolar caliber in the highest quartile (quartile 4). These findings show that the presence of microvascular disease in the retina increases the likelihood of CKD associated with hypertension and suggest that examination of the retinal vasculature may aid in stratification of CKD risk in hypertensive patients.

Diabetes mellitus as a prothrombotic condition

Diabetes mellitus (DM) is characterized by fasting hyperglycaemia and a high risk of atherothrombotic disorders affecting the coronary, cerebral and peripheral arterial trees. The risk of myocardial infarction (MI) is 3-5 fold higher in Type 2 DM and a DM subject with no history of MI has the same risk as a non-DM subject with a past history of MI. In total around 70% of deaths are vascular with poorer outcomes to both acute events and cardiological interventions. It was proposed that clustering of vascular risk factors (hyperinsulinaemia, dysglycaemia, dyslipidaemia and hypertension) around insulin resistance (IR) accounted for the increase in risk with Type 2 DM. The importance of this became apparent with the recognition that risk clustering occurs in normoglycaemic and impaired glucose tolerance (IGT) subjects with IR, in total around 25% of the population in addition to long-standing Type 1 subjects with renal disease. Evidence indicates that thrombotic risk clustering also occurs in association with IR, suppression of fibrinolysis due to elevated concentrations of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1) is invariable with IR and there is evidence that this is regulated by the effects of triglyceride on the PAI-1 gene promoter. Other studies indicated that prothrombotic risk (coagulation factors VII, XII and fibrinogen) also associates with the IR syndrome. The development of endothelial cell dysfunction with suppression of nitric oxide and prostacyclin synthesis, combined with platelet resistance to the anti-aggregatory effects of these hormones leads to loss of control over platelet activation. In addition, hyperglycaemia and glycation have marked effects on fibrin structure function, generating a clot which has a denser structure, resistant to fibrinolysis. The combination of increased circulating coagulation zymogens, inhibition of fibrinolysis, changes in fibrin structure/function and alterations in platelet reactivity creates a thrombotic risk clustering which underpins the development of cardiovascular disease.

Incidence of Coronary Heart Disease in Type 2 Diabetic Men and Women

Cardiovascular disease (CVD) is the main cause of morbidity/mortality in diabetes. We set forth to determine incidence and identify predictors (including microvascular complications and treatment) of first coronary heart disease (CHD) event in CVD-free type 2 diabetic patients. A cohort of 6,032 women and 5,612 men, sampled from a nationwide network of hospital-based diabetes clinics, was followed up for 4 years. Baseline assessment included retinopathy, nephropathy, and foot ulcers. First CHD events (myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and electrocardiogram-proven angina) were analyzed for 29,069 person-years. The age-standardized incidence rate (per 1,000 person-years) of first CHD event (n = 881) was 28.8 (95% CI 5.4-32.2) in men and 23.3 (20.2-26.4) in women. Major CHD (myocardial infarction, coronary artery bypass grafting, and percutaneous transluminal coronary angioplasty) was less frequent in women (5.8 [4.3-7.2]) than in men (13.1 [10.9-15.4]; a sex ratio of 0.5 [0.4-0.6]). Incidence rates of all outcomes were higher in patients with microvascular complications (for major CHD, age-adjusted rate ratios were 1.6 [1.2-2.21] in men and 1.5 [1.0-2.2] in women). By multivariate Cox analysis, age and diabetes duration were risk predictors common in both sexes. In men, glycemic control and treated hypertension were additional independent risk factors, but residing in the south was associated with a significant 29% risk reduction. In women, higher triglycerides/lower HDL cholesterol and microvascular complications were independent risk factors. In CVD-free patients with type 2 diabetes, risk of first CHD event depends on sex, geographic location, and presence of microvascular disease. Hyperglycemia and hypertension, particularly in men, and diabetic dyslipidemia, especially in women, are risk factors amenable to more aggressive treatment.

Diabetes, glucose level, and risk of sudden cardiac death

The prevalence of diabetes mellitus in industrialized countries is rapidly increasing, and diabetes is suspected to carry a particular high risk for sudden cardiac death (SCD). We conducted a population-based case-control study at Group Health Cooperative. Cases (n=2040) experienced out-of-hospital cardiac arrest due to heart disease between 1980 and 1994. Controls (n=3800) were a stratified random sample of enrollees. Diabetes status was classified into four exclusive groups: (i) no diabetes, (ii) borderline, (iii) diabetes without microvascular disease (retinopathy or proteinuria), and (iv) diabetes with microvascular disease. When compared with no diabetes, we observed progressively higher risk of SCD associated with borderline diabetes [Odds ratio (OR)=1.24 (0.98-1.57)], diabetes without microvascular disease [OR=1.73 (1.28-2.34)], and diabetes with microvascular disease [OR=2.66 (1.84-3.85)], after adjustment for potential confounders (P-value for trend <0.001). Higher glucose levels were also associated with the risk of SCD both in the absence and in the presence of microvascular disease. However, subjects with microvascular complications but with glucose level <7.7 mmol/L were not at significant increased risk of SCD. These results emphasize the role of diabetes as a strong risk factor for SCD and outline the importance of glucose level at every stage of diabetes severity.

Associations between inflammatory markers, traditional risk factors, and complications in patients with type 2 diabetes mellitus

Objective: Inflammatory markers predict cardiovascular events in a wide range of patients. Two factors, fibrinogen (FIB) and high-sensitivity C reactive protein (CRP), are currently entering clinical practice as cardiovascular risk predictors. In patients with type 2 diabetes mellitus, we sought to examine the relationship between macrovascular disease, urinary albumin/creatinine ratio (ACR), and FIB or CRP, as well as the relationship of FIB and CRP with traditional risk predictors of these complications of diabetes. Methods: In 202 consecutive patients with type 2 diabetes mellitus from a diabetes clinic, clinical and biochemical data were obtained and a cross-sectional analysis was performed. Results: Patients with macrovascular disease had higher FIB ( P=.02) but not higher CRP. They were older, more likely to have retinopathy or elevated serum creatinine, had higher ACR and lower HDL cholesterol. They were more likely to be treated with statins, β-blockers, and ASA. Adjustment for statin therapy did not result in significant differences in CRP levels according to macrovascular disease status. Both FIB ( P=.01) and CRP ( P=.02) were significantly higher in patients with ACR whose values were in the proteinuria range. In multivariate analysis, both FIB ( P=.001) and CRP ( P=.03) were positively correlated with ACR, but no association was seen between CRP and ACR when FIB was entered in the model. Other factors positively associated with ACR were age, diastolic blood pressure, retinopathy, and hemoglobin A1c (HbA1c). FIB and CRP were strongly correlated ( R=.49, P≤.001) and this effect was independent of statin therapy. CRP was positively associated with body mass index (BMI), serum triglycerides, and sulfonylurea therapy and negatively associated with metformin therapy. Patients on statin therapy had significantly higher FIB and lower CRP. Women on hormone replacement therapy (HRT) had significantly lower FIB and higher CRP. Conclusions: In patients with diabetes: (1) the two markers, FIB and CRP, are interrelated; (2) FIB is significantly associated with presence of microvascular disease, independent of CRP; (3) CRP is strongly associated with metabolic factors but not with complications of diabetes, independently of FIB; (4) statins and HRT were divergently associated with CRP and FIB as HRT was associated with lower FIB and higher CRP, while statins showed the reverse association; and (5) CRP and FIB provide different information about the characteristics and consequences of diabetes mellitus because of divergent associations with biological indicators and therapeutic agents.

Limited joint mobility in diabetes mellitus.

The relationship of limited joint mobility and finger joint contractures in diabetics to age of onset, duration, and control of diabetes has not been established. We measured the mobility of metacarpophalangeal, wrist, elbow, and ankle joints and assessed the prevalence of finger joint contractures in 254 young diabetics and 110 controls. The presence of microvascular disease was assessed by ophthalmoscopy and urine analysis for proteinuria. An estimate of long-term diabetic control was obtained from a postal questionnaire. A generalised reduction in joint mobility was present in diabetics of all ages two years after diagnosis. The reduction in joint mobility in controls between the ages of 12 and 13 was exaggerated in the diabetics. Diabetics diagnosed before puberty were more severely affected than those with a postpubertal onset, independent of duration of diabetes. Finger joint contractures were a significant feature of longstanding diabetics (nine years or more duration) only.

β-thromboglobulin and fibrinopeptide a in diabetes mellitus as markers of vascular damage

Beta-thromboglobulin (BTG) and fibrinopeptide A (FpA) were studied in 68 non-insulin dependent diabetic patients (NIDD) aged 32-81 with a mean duration of diabetes of 9 +/- 0.8 SEM years and 44 healthy controls, comparable for age and sex. Diabetic patients were subdivided into subsets according to the presence of microvascular disease, macrovascular disease or the absence of these lesions. Patients with microangiopathy (micro- and/or macrovascular disease) had higher HbA1 (a-c) (p less than 0.01), higher blood pressure (p less than 0.05) than both healthy controls and uncomplicated diabetics. Plasma BTG was higher in diabetic patients than in healthy controls (p less than 0.02), and was higher in complicated than in non-complicated diabetic subjects. Fpa was higher in complicated than in non-complicated diabetes (p less than 0.05). No differences were observed between the two subsets of complicated patients. In conclusion, we have shown that increased plasma- and platelet-BTG levels are present in non-insulin dependent diabetic subjects, with normal renal function and that plasma BTG is higher in patients with than in those without vascular disease. Fibrinopeptide A, a sensitive marker of in vivo fibrin formation, was significantly increased in NIDD with vascular complications.

Aortocoronary bypass in the diabetic patient

One hundred twelve patients undergoing aortocoronary bypass—35 with diabetes of adult onset and 77 without diabetes—were studied to determine whether diabetic patients have additional operative risks and greater operative mortality and whether their coronary disease differs from that of nondiabetic patients. Among the diabetic patients there was a greater prevalence of preoperative unstable angina, prior myocardial infarction and class IV functional disability (New York Heart Association criteria). The major coronary arteries angiographically and at operation appeared similar in both groups. The blood flow rates measured in aortocoronary bypass vein grafts were similar in both groups, raising doubt about the presence of microvascular disease in the myocardium of the diabetic patient. Preliminary follow-up results demonstrated relief of anginal symptoms in 76 percent of diabetic and 78 percent of nondiabetic patients. The operative mortality rate of 9 percent in diabetic and 4 percent in nondiabetic patients occurred among the first 40 patients in the series; no patient in either group has died in the immediate postoperative period during the last 18 months of the study. Aortocoronary bypass should be recommended to diabetic patients with symptomatic coronary arteriosclerosis using the same criteria for operability applied to the nondiabetic population.