Showing papers by "Anushka Patel published in 2008"

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

Abstract: BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. RESULTS: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). CONCLUSIONS: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)

The relationship between proteinuria and coronary risk: A systematic review and meta-analysis

Abstract: Background: Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease Methods and Findings: A meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants Two independent researchers extracted the estimates of association between proteinuria (total urinary protein >300 mg/d), microalbuminuria (urinary albumin 30-300 mg/ d), macroalbuminuria (urinary albumin >300 mg/d), and risk of coronary disease from individual studies These estimates were combined using a random-effects model Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal) The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 147, 95% confidence interval [CI] 123-174) after adjustment for known risk factors For albuminuria, there was evidence of a dose-response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 147, 95% CI 130-166) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 217, 187-252) Sensitivity analysis indicated no important differences in prespecified subgroups Conclusion: These data confirm a strong and continuous association between proteinuria and subsequent risk of coronary heart disease, and suggest that proteinuria should be incorporated into the assessment of an individual's cardiovascular risk

Prospective observational study of acute coronary syndromes in China: practice patterns and outcomes

Abstract: Objective: To describe the investigation and management of patients admitted to hospitals in China with suspected acute coronary syndromes (ACS) and to identify potential areas for improvement in practice. Design: A multicentre prospective survey of sociodemographic characteristics, medical history, clinical features, in-hospital investigations, treatment practices and major events among patients with suspected ACS. Setting: Large urban public hospitals. Patients: Consecutive patients admitted to in-patient facilities with a diagnosis of suspected acute myocardial infarction (MI) or unstable angina pectoris. Main outcome measures: Myocardial infarction/re-infarction, heart failure, death. Results: Between September 2004 and May 2005, data were collected prospectively from 2973 patients admitted to 51 hospitals in 18 provinces of China. An initial diagnosis of ST elevation MI, non-ST elevation MI and unstable angina was made in 43%, 11% and 46% of patients, respectively. Diagnosis was inconsistent with objective measures in up to 20% of cases. At both tertiary and non-tertiary centres, there was little evidence that clinical risk stratification was used to determine the intensity of investigation and management. The mortality rate during hospitalisation was 5% overall and similar in tertiary and non-tertiary centres, but reported in-hospital re-infarction rates (8%) and heart failure rates (16%) were substantially higher at non-tertiary centres. Conclusion: This study has identified a number of areas in the management of ACS patients, including diagnosis and risk stratification, which deviate from current guidelines. These findings will help inform the introduction of widely used quality improvement initiatives such as clinical pathways.

Body mass index is an independent determinant of left atrial size.

Abstract: Background Obesity is a risk factor for atrial fibrillation (AF) but the mechanisms underlying this association are unclear. We aimed to assess whether body mass index (BMI) is an independent determinant of left atrial size, in subjects in sinus rhythm. Methods Subjects were consecutive ambulatory patients aged ≥18 years who underwent outpatient transthoracic echocardiography at a major metropolitan teaching hospital in Sydney, Australia. At the time of examination, age, sex, height and weight were measured. Left atrial (LA) area was measured on ultrasound by planimetry. Left ventricular (LV) function and LV posterior wall thickness were measured by M-mode. Results Of 4859 consecutive subjects who underwent outpatient echocardiography at our institution over a three-year period, we analysed echocardiographic data from 2534 aged ≥18 years with confirmed sinus rhythm, normal LV contractility and no evidence of significant aortic or mitral valve disease. In these subjects (age 47±16.6 years, BMI 27.1±6.1, 53% male), BMI was a significant predictor of LA size ( p 2 in those with normal BMI, 20.7±4.5cm 2 in the overweight and 22.3±4.1cm 2 in obese subjects ( p for trend Conclusions Obesity is associated with increased left atrial size in subjects undergoing clinically indicated echocardiography, independent of the effects of left ventricular size and posterior wall thickness. This may contribute, at least in part, to the rising incidence of atrial fibrillation in the community.

Retinal Vascular Lesions in Patients of Caucasian and Asian Origin With Type 2 Diabetes: Baseline results from the ADVANCE Retinal Measurements (AdRem) study

Abstract: OBJECTIVE —The objective of this study was to describe prevalent vascular retinal lesions among patients with type 2 diabetes enrolled in the ADVANCE Retinal Measurements (AdRem) study, a substudy of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS —Seven-field stereoscopic photographs of both eyes were obtained at the baseline assessment of the ADVANCE trial. All photographs were graded in a central reading center. Gradable retinal images were received from 1,605 patients. RESULTS —The number of patients with any retinopathy (Early Treatment of Diabetic Retinopathy Study [ETDRS] score ≥20) was 645 (40.2% [95% CI 37.8–42.6]); of these, 35 (2.2% [1.6–3.0]) had severe diabetic retinopathy (ETDRS score ≥50). Focal arterial narrowing, venous beading, and arteriovenous nicking were present in 3.8, 5.1, and 9.8% of participants, respectively. Among participants included in this study, Chinese and South-Asian patients had more retinopathy than Caucasians, as defined both by ETDRS score (49.4, 46.0, and 31.3%, respectively; P P CONCLUSIONS —Using a sensitive diagnostic procedure, more than one-third of patients with type 2 diabetes enrolled in the AdRem study had retinal lesions at baseline. Despite differences in prevalence and severity of retinopathy among Chinese, South-Asian, and Caucasian patients included in this study, the cross-sectional associations among established risk factors for retinopathy and retinal lesions were similar across ethnic groups.

Elevated total cholesterol: Its prevalence and population attributable fraction for mortality from coronary heart disease and ischaemic stroke in the Asia-Pacific region

Abstract: Background: About half of the world s cases of cardiovascular disease occur in the Asia-Pacific region. The contribution of serum total cholesterol (TC) to this burden is poorly quantified. Design: The most recent nationally representative data on TC distributions for countries in the region were sought. Individual participant data from 380 483 adults in the Asia Pacific Cohort Studies Collaboration were used to estimate associations between TC and cardiovascular disease. Methods: High TC was defined as ≥6.2mmol/l, and nonoptimal TC as ≥ 3.8mmol/l. Hazard ratios for fatal coronary heart disease (CHD) and ischaemic stroke (IS) were found from Cox models. Sex-specific population attributable fractions for high TC and nonoptimal TC were estimated for each country. The former used conventional methods, based on single measures of TC and a fixed dichotomy of risk strata; the latter took account of the continuous positive association between TC and both CHD and IS and regression dilution. Results: Data were available from 16 countries. Where reported, the prevalence of high TC ranged from 4 to 27%. The fraction of fatal CHD and IS attributable to high TC ranged from 0 to 14% and 0 to 15%, respectively. Although leaving the relative ranking of countries much the same, the fractions estimated for nonoptimal TC were typically at least twice as big, ranging from 0 to 47% and 0 to 35%, respectively. Conclusion: Conventional methods for estimating disease burden severely underestimate the effect of TC. Cholesterol-lowering strategies could have a tremendous effect in reducing cardiovascular deaths in this populous region.

Cardiovascular risk management at a Maori-led Primary Health Organisation--findings from a cross-sectional audit.

Abstract: AIM To examine the cardiovascular disease (CVD) risk profile and management for the first 12 months of an electronic risk assessment program at Tamaki Healthcare, Auckland. METHODS An audit of risk assessment and medication data supplemented by a manual case record review. RESULTS 1522 people were screened representing around 15.5% of the eligible population. Of the 1420 people with data available, 248 (17.5%) had a calculated 5-year CVD risk > or = 15% and another 177 (12.5%) had previous CVD. Maori were significantly more likely to be at high CVD risk than non-Maori (OR 2.07 (1.51-2.84); p<0.001). For Pacific peoples (mostly of Samoan, Tongan, Niuean, Fijian, or Cook Islands origin) there was no increased likelihood of high CVD risk. Medication data were available for 399 (95.5%) people at high CVD risk. Prescribing rates for this group were 78.1% for blood pressure lowering, 71.9% for lipid-lowering, 65.3% for anti-platelet ,and 50.3% for all three therapies. Whilst this group may represent the better end of the management spectrum, success in achieving treatment targets was modest. For 451 people with either diabetes or established CVD, 65.9% and 66.1% were not meeting blood pressure and lipid management recommendations respectively. There were very few disparities in prescribing rates and attainment of target levels by ethnic group. CONCLUSION This study has shown that a primary care electronic risk assessment program can be rapidly implemented within 12 months. Although the sample may not be representative due to a small proportion screened so far, major disparities in risk factor prevalence rates were found- particularly for Maori. Furthermore, substantial guideline-practice gaps were encountered in the appropriate prescribing of cardiovascular medicines and attainment of recommended targets. Several Tamaki Healthcare initiatives to address these findings are discussed.

The Relationship between Proteinuria and Coronary Risk: A Systematic Review and

Abstract: Background Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined. This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk. We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease. Methods and Findings A meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk. MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease. Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants. Two independent researchers extracted the estimates of association between proteinuria (total urinary protein .300 mg/d), microalbuminuria (urinary albumin 30–300 mg/ d), macroalbuminuria (urinary albumin .300 mg/d), and risk of coronary disease from individual studies. These estimates were combined using a random-effects model. Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size. A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal). The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23–1.74) after adjustment for known risk factors. For albuminuria, there was evidence of a dose–response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 1.47, 95% CI 1.30–1.66) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 2.17, 1.87–2.52). Sensitivity analysis indicated no important differences in prespecified subgroups. Conclusion

Efficacy and safety of fixed combination of perindopril and indapamide in type 2 diabetes: results from ADVANCE in context of available evidence.

Abstract: OBJECTIVES: The ADVANCE trial was designed to determine the effects of routine blood pressure lowering using a fixed combination of perindopril-indapamide on major vascular outcomes in patients with type 2 diabetes, regardless of initial blood pressure levels or the use of other blood pressure-lowering drugs, including angiotensin-converting enzyme inhibitors. METHODS: After a 6-week run-in period, 11,140 high-risk individuals with type 2 diabetes were randomized to fixed combination perindopril-indapamide or matching placebo, in addition to current therapy. The two primary outcomes were composites of major macrovascular and major microvascular events, analysed jointly and separately by intention to treat. RESULTS: The reduction in blood pressure in participants assigned to active treatment was 5.6/2.2 mmHg greater than that observed in the control group. Active treatment reduced the risk of the combined primary outcome, a major macrovascular or microvascular event by 9% (P = 0.041) and resulted in a 14% (P = 0.025) reduction in all-cause mortality and an 18% (P = 0.027) reduction in cardiovascular mortality. There were reductions of 14% (P = 0.02) in total coronary events and 21% (P < 0.0001) in total renal events. The treatment was well tolerated, with 73% and 74% of patients in the active treatment and placebo groups still adherent to randomized therapy after an average of 4.3 years of follow-up. CONCLUSIONS: Routine treatment with the fixed combination of perindopril and indapamide was well tolerated and reduced the risk of death and major vascular events, regardless of the initial blood pressure level or concomitant treatments received. The results suggest that for every 79 patients treated in this manner, one death would be avoided over 5 years.

Advances in reducing the burden of vascular disease in type 2 diabetes

Abstract: 1. The epidemic of diabetes is accelerating and the World Health Organization estimates that the number of people affected worldwide will grow from 171 million in 2000 to 366 million by 2030. 2. The main causes of death and disability in individuals with type 2 diabetes are macrovascular and microvascular disease, and blood pressure is one of the main determinants of vascular complications in this population. 3. While randomized trials have demonstrated that blood pressure lowering reduces vascular complications in subjects with type 2 diabetes and hypertension, ADVANCE was designed to determine whether the addition of a fixed combination of perindopril and indapamide, on top of comprehensive and effective cardiovascular treatments and glucose control therapy, would produce further benefits, irrespective of the initial blood pressure. 4. The blood pressure lowering arm of ADVANCE has demonstrated that the simple addition of the fixed combination of perindopril and indapamide compared to matching placebo, significantly reduces combined macrovascular and microvascular complications by 9%, all-cause mortality by 14% and cardiovascular death by 18%. It also reduces total coronary events by 14% and all renal events and microalbuminuria by 21%. 5. Similar benefits were observed in participant sub-groups characterized by age, sex, baseline blood pressure, previous vascular diseases and concomitant cardiovascular therapy including blood pressure lowering therapy. 6. Successful implementation of this treatment, with a single combination tablet of perindopril and indapamide, should be practical and affordable in most clinical settings worldwide and has the capacity to save countless lives and to reduce the burden of coronary disease and renal disease burden among millions of people with type 2 diabetes.

High prevalence of chronic kidney disease in

Abstract: We describe the prevalence of stage III and IV chronic kidney disease in Thailand from a representative sample of individuals aged 35 years and above using a stratified, multistage, cluster-sampling method. Population estimates were calculated by applying sampling weights from the 2000 Thai census. Glomerular filtration rates were estimated from serum creatinine using the Cockroft–Gault and the simplified Modification of Diet in Renal Disease (MDRD) formulae. The prevalence of stage III disease among individuals aged 35 years and above was estimated to be about 20% using the Cockroft–Gault formula and about 13% from the MDRD formula. Stage IV disease was present in about 0.9 and 0.6% of this population using the respective formulae. The highest prevalence rates were observed in less well-developed rural areas and the lowest in developed urban areas. The prevalence of chronic kidney disease was significantly higher than that reported in individuals over 40 years old from the United States for both stage III and IV disease and higher than the reported incidence in Taiwan and Australia. This high prevalence of chronic kidney disease in Thailand has obvious implications for the health of its citizens and for the allocation of health-care resources.

Why is there more heat than light concerning the polypill

Abstract: Watts’s question—why are there still so few polypill trials?—is reasonable.1 In 2001 epidemiologist Richard Peto facilitated a meeting between the World Health Organization and the Wellcome Trust to discuss development of fixed dose combination products in secondary prevention of cardiovascular disease.2 Yusuf noted the potential for a combination treatment to reduce cardiovascular risk by three quarters in the Lancet in 2002.3 …