Martin K. Rutter

Significance of silent ischemia and microalbuminuria in predicting Coronary events in asymptomatic patients with type 2 diabetes

OBJECTIVES The aim of this study was to investigate the relationships between future coronary heart disease (CHD) events and baseline silent myocardial ischemia (SMI) and microalbuminuria (MA) in subjects with type 2 diabetes (T2D) free from known CHD. BACKGROUND Coronary heart disease is often asymptomatic in subjects with diabetes. There is limited information on the prognostic value of SMI and MA in this group. METHODS Eighty-six patients with T2D and no history of CHD were studied (43 with MA individually matched with 43 normoalbuminuric patients; mean [SD] age 62 [+/-7] years, 62 men). Metabolic assessment, three timed overnight urine collections for albumin excretion rate, a treadmill exercise test and ankle brachial index (ABI) were performed at baseline. Patients were followed for 2.8 years. RESULTS Forty-five (52%) patients had SMI during treadmill testing. At review, there had been 23 coronary (CHD) events in 15 patients. Univariate Cox regression analysis showed that CHD events were significantly related to baseline ABI (p = 0.014), SMI (p = 0.020), MA (p = 0.046), 10-year Framingham CHD risk >30% (p = 0.035) and fibrinogen (p = 0.026). In multivariate analysis, SMI was the strongest independent predictor of CHD events (p = 0.008); risk ratio (95% confidence interval) for SMI: 21 (2 to 204). In the prediction of CHD events, SMI showed higher sensitivity and positive predictive value than MA or Framingham calculated CHD risk. CONCLUSIONS The presence of baseline SMI and MA are associated with future CHD events in asymptomatic patients with T2D and may be of practical use in risk stratification.

Microalbuminuria is more frequent in South Asian than in European origin populations: a comparative study in Newcastle, UK

Aims We aimed to compare levels of urinary albumin excretion and the prevalence of microalbuminuria in UK South Asians and Europeans. Microalbuminuria predicts cardiovascular disease in European origin populations, but evidence from the general population of South Asians is lacking. Coronary heart disease (CHD) mortality is 40–50% higher in UK South Asians compared with the whole population, for reasons that are incompletely understood.

Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non-insulin-dependent diabetes mellitus.

Microalbuminuria is an increase in urinary albumin not detected by conventional dipstick testing and is present in 20% of patients with non-insulin-dependent diabetes mellitus (NIDDM). Mortality in NIDDM patients with microalbuminuria is 60% at 8 years and is mainly due to cardiovascular disease. Because many deaths occur without warning symptoms, we have compared the prevalence and severity of silent myocardial ischemia in asymptomatic NIDDM patients with and without microalbuminuria. We have performed a cross-sectional, case-control study of asymptomatic NIDDM patients attending hospital diabetes clinics. Forty-three patients with microalbuminuria were matched for age, gender, diabetes duration, and smoking status with 43 normoalbuminuric patients. A symptom-limited exercise stress test was performed and reported blind to patient status. The degree of electrocardiographic ST-segment depression, exercise time, work performed, and maximum heart rate with exercise were recorded. Patients with microalbuminuria had a higher prevalence of ischemic response (>1 mm ST depression) (65% vs 40%, p = 0.016), reduced total exercise time (5 vs 7 minutes, p <0.001), reduced work (6 vs 8 METs, p <0.001), and reduced age-predicted maximum heart rate (94% vs 101%, p = 0.004). In multiple logistic regression, albumin excretion rate was shown to be the strongest independent predictor of ischemic response (p = 0.03). Silent myocardial ischemia is common in asymptomatic NIDDM patients but is more common in those with microalbuminuria. In these subjects, the higher prevalence of ischemic response at low workloads suggests a higher probability of future coronary events, and possibly a higher probability of potentially treatable coronary artery disease.

Increased left ventricular mass index and nocturnal systolic blood pressure in patients with Type 2 diabetes mellitus and microalbuminuria

Aims To compare left ventricular mass (LVM) index and function in patients with Type 2 diabetes mellitus with and without microalbuminuria and to investigate the clinical determinants of left ventricular hypertrophy.

Impaired Glucose Tolerance and Insulin Resistance in Heart Failure: Underrecognized and Undertreated?

BACKGROUND A link between diabetes mellitus (DM) and heart failure (HF) has been well-recognized for more than a century. HF is also closely linked to abnormal glucose regulation (AGR) and insulin resistance (IR) in patients without DM and, similarly, these conditions commonly coexist. In epidemiological studies, each condition appears to predict the other. The prevalence of AGR/IR in HF patients without DM is significantly underrecognized and, as yet, the optimal method for screening for these abnormalities in the outpatient setting is unclear. METHODS AND RESULTS The purpose of this review is to overview the prevalence and prognostic impact of AGR and IR in HF patients without DM and discuss potential pathophysiological pathways that link these conditions with HF. The severity of glucose intolerance in patients with HF correlates with functional and clinical severity of HF and is an independent predictor of an adverse outcome. It is thought that changes in cardiac metabolism, including a switch from glucose metabolism toward fatty acid metabolism, may in part contribute to the pathophysiological processes associated with HF patients with AGR/IR. CONCLUSIONS We discuss how pharmacological targeting of metabolic pathways in the myocardium of these patients with HF may represent novel therapeutic strategies in these at-risk patients.

Enhanced external counterpulsation for the relief of angina in patients with diabetes: safety, efficacy and 1-year clinical outcomes

Abstract Background Patients with diabetes are at greater risk for coronary events, yet they are less likely to benefit from revascularization than those without diabetes. Enhanced external counterpulsation has recently emerged as a treatment option for select patients with chronic stable angina. Methods We examined baseline characteristics, angina response, and cardiac outcomes of patients with diabetes mellitus treated with Enhanced External Counterpulsation (EECP) for chronic stable angina. Data were collected from patients enrolled in the International EECP Patient Registry (IEPR) before and after a course of EECP, and at 1 year after completion of treatment. Results Of 1532 IEPR patients studied, 43% had diabetes mellitus at baseline. Patients with diabetes were experiencing, on average, 11 episodes of angina per week. Most had been revascularized with prior percutaneous coronary intervention or coronary artery bypass graft surgery (86%) and most were considered unsuitable for either additional procedure (87%). Treatment was completed as prescribed in 79% of patients (mean, 32 hours). Immediately after EECP, 69% of patients with diabetes demonstrated a reduction in angina of ≥1 Canadian Cardiovascular Society angina class. After 1 year, maintenance of angina reduction was reported in 72% of patients with diabetes. Quality of life was significantly improved. Despite a high-risk profile among the diabetic group in this study, 1-year mortality was similar to coronary intervention registry populations. Conclusion This study suggests that in select patients with diabetes, EECP can be a safe, effective, well-tolerated treatment option for the relief of angina.

Impact of the atherosclerotic process in patients with diabetes.

Abstract Between 120 and 140 million people suffer from diabetes mellitus (type 1 and type 2) worldwide, and this number may well double by the year 2025. Patients with diabetes are at increased risk of atherosclerosis and its clinical sequelae: coronary, peripheral vascular, and cerebrovascular diseases. Concurrently, the most common cause of death in persons with diabetes is myocardial infarction. The pathogenesis, progression, and epidemiology of atherosclerotic disease are distinct in patients with diabetes. Atherosclerosis can develop much earlier in life, and at an accelerated rate, compared with non-diabetic individuals. One of the factors responsible for increased atherosclerosis is related to the atherogenic lipid profile in diabetes. The pathobiological processes that are responsible for transforming dormant atherosclerotic plaques into active rupture-prone plaques may be enhanced in diabetes as well. It follows that a major challenge in the treatment of patients with diabetes is to reduce the risk of atherosclerotic disease. The third National Cholesterol Education Program (NCEP) report recently recommended that the management of dyslipidaemia in patients with diabetes should be as aggressive as in those with established coronary heart disease (CHD). The NCEP Adult Treatment Panel III guidelines recommend statins for patients at elevated risk for CHD.

The changing costs and benefits of screening for asymptomatic coronary heart disease in patients with diabetes.

Aggressive medical therapy can be justified in most patients with diabetes, but there may be some higher-risk asymptomatic patients who could benefit from revascularization and/or medical therapy for myocardial ischemia. Silent myocardial ischemia (SMI) might be used to identify these high-risk individuals. In this Review we define SMI as objective evidence of ischemia from any noninvasive test occurring in an asymptomatic patient. We outline what is known about asymptomatic coronary heart disease (CHD) in diabetes and how this relates to SMI. We examine how SMI predicts angiographic CHD and CHD events, and we describe the changing role of CHD screening as reflected by various guidelines. We identify the recent research suggesting that there may be substantial numbers of high-risk asymptomatic patients who have diabetes with undiagnosed CHD and who could benefit from more-active intervention; however, with the recent advances in medical therapy, and the uncertain benefits of screening, current guidelines strongly discourage this practice, except in limited clinical situations, such as before major surgery. Carefully conducted clinical trails using state-of-the-art investigations and therapy in well-characterized patients with diabetes are urgently required to inform physicians on when and how to intervene.

Autonomic neuropathy in asymptomatic subjects with non-insulin-dependent diabetes mellitus and microalbuminuria

Patients with non-insulin-dependent diabetes mellitus (NIDDM) and microalbuminuria (MA) are at increased risk of early death. In NIDDM patients without evidence of heart disease, we examined the links between MA and autonomic neuropathy (AN) and reduced heart rate variability (HRV), both of which have been linked to a poor prognosis. We have studied 43 asymptomatic NIDDM patients with MA and have matched them with 43 normoalbuminuric patients for age, gender, diabetes duration, and smoking status. AN was assessed by heart rate changes to deep breathing, Valsalva, and posture and blood pressure changes to posture and hand grip. Twentyfour hour Holter monitoring was used to evaluate HRV.Patients with MA showed evidence of AN and reduced HRV when compared with normoalbuminuric patients. In multivariate analysis, with measures of AN and HRV as outcome variables, Logc albumin excretion rate was a significant independent predictor but stronger predictors were the presence of diabetic retinopathy, age, body mass index, claudication, alcohol consumption, and calcium channel blocker use.The presence of MA is linked to AN and reduced HRV in asymptomatic NIDDM patients. The nature of the relationship is complex, involving multiple relationships with other clinical parameters.

QT prolongation in patients with Type 2 diabetes and microalbuminuria.

Abstract. The link between microalbuminuria and premature death in Type 2 diabetes is not fully explained by conventional cardiovascular risk factors. We aimed to determine if QT prolongation and/or dispersion are linked to microalbuminuria in patients with Type 2 diabetes and to investigate their associations with other risk factors. We have studied asymptomatic patients with Type 2 diabetes with no clinical evidence of coronary disease (43 with microalbuminuria matched with 43 normoalbuminuric patients). Rate-corrected maximum QT interval (QTc max) was greater in the microalbuminuric group [mean (SD): 450 (23) vs 440 (20) ms1/2, p = 0.046] as was the proportion of patients with QTc max > 440 ms (67 % vs 38 %, p = 0.01). Rate-corrected QT dispersion (QTcd) was similar in the two groups [57 (21) vs 53 (23) ms1/2, p = 0.41]. Linear regression analysis showed that QTc max and/or QTcd were not strongly linked to albumin excretion rate but more strongly to factors associated with microalbuminuria such as blood pressure and factor XIIa. Our findings support the hypothesis that QT prolongation and microalbuminuria have common determinants in Type 2 diabetes. QT prolongation may contribute to the increased mortality observed in microalbuminuric subjects with Type 2 diabetes.