Thi qar university/college of medicine

Incidence of cardiovascular disease in Type 2 DM

Supervisor : Dr. Bassim Athaib

Done by:Rawan kadem

Tuka Jawad

Background

The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.

Abstract

Diabetes is a major risk factor for heart disease, and heart disease is responsible for substantial morbidity and mortality among people living with diabetes. The diabetic metabolic milieu predisposes to aggressive obstructive coronary artery disease that causes heart attacks, heart failure and death. Furthermore, diabetes can be associated with heart failure, independent of underlying coronary artery disease, hypertension or valve abnormalities. The pathogenesis of the vascular and myocardial complications of diabetes is, as yet, incompletely understood. Although a number of medical and surgical approaches can improve outcomes in diabetic patients with cardiovascular disease, much remains to be learned in order to optimize approaches to these

Findings

Our cohort consisted of 50 individuals, of whom 35 had cardiac disease with DM and 15 did not have cardiac disease in type 2 diabetes. We observed 35 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1–10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 16·2%] and heart failure (14·1%] Type 2 diabetes was positively associated with peripheral arterial disease (ischaemic stroke (1·72 [1·52–1·95]), stable angina (1·62 [1·49–1·77]), heart failure (1·56 [1·45–1·69]), and non-fatal myocardial infarction (1·54 [1·42–1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35–0·59]) and subarachnoid haemorrhage (0·48 [0·26–0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76–1·19]).Interpretation

Heart failure and p

Interpretation

Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design

Introduction

The cardiovascular complications of diabetes present a formidable challenge because of the high prevalence of diabetes and the adverse effects of cardiovascular disease on quality of life and survival. Recent statistics from the Centers for Disease Control estimate that heart disease is noted on more than two-thirds of diabetes-related death certificates among people 65 years or older [1]. Diabetes is a major risk factor for obstructive coronary artery disease (CAD), leading to myocardial infarction and heart failure. Diabetes is also associated with an increased risk of heart failure in the absence of valvular abnormalities, alcoholism, congenital anomalies, hypertension, or obstructive CAD. This disorder is known as diabetic cardiomyopathy. In this review, we discuss the epidemiology, pathogenesis and management of coronary artery and myocardial complications that affect diabetics, with an emphasis on data from human studies. Insights from in vitro and in vivo animal models will be discussed elsewhere in this issue.

Patients with type 2 diabetes are at increased risk of cardiovascular diseases and associated clinical complications.Although type 2 diabetes has become an increasingly common disease, estimated to affect 380 million people worldwide by 2025,the incidence of myocardial infarction and stroke has declined rapidly during the past few decades. However, myocardial infarction and stroke continue to be chosen as primary outcomes of major type 2 diabetes trials (appendix).To reliably estimate the benefit of type 2 diabetes prevention and treatment in trials, or the future burden of type 2 diabetes-associated diseases for health-care planning, a better understanding of how type 2 diabetes affects the risk of other acute and chronic cardiovascular manifestations is needed.

Previous studies have not compared the relation between type 2 diabetes and a wide range of cardiovascular outcomes such as heart failure, peripheral arterial disease, abdominal aortic aneurysm, and ventricular arrhythmias in the same study, but have instead focused on a narrower range of disease outcomes, usually just one or two.Such comparisons need large study samples to reliably estimate associations for rare outcomes. Since early reports were

published,5results of several small studies have shown that the effect of type 2 diabetes on cardiovascular manifestations differs according to the specific cardiovascular outcome measuredand the sex of the participant.However, these studies were not designed to reliably assess associations with several cardiovascular diseases or across population subgroups.

We have addressed these gaps in knowledge by establishing a large prospective cohort using linked electronic health records,which combine information about diabetes diagnosis, risk factors, and medication use with future cardiovascular events. Our objective was to investigate and compare associations between type 2 diabetes and future risk of 12 of the most common initial cardiovascular presentations in men and women.

Procedures

We defined individuals as having diabetes at baseline (type 1, type 2, or uncertain type) on the basis of coded diagnoses recorded in CPRD or hospital episode statistics at or before study entry (appendix). Participants who developed new-onset diabetes during follow-up were analysed according to their baseline status of no diabetes. We compared people with type 2 diabetes to those without diabetes; we excluded people with type 1 diabetes or diabetes of uncertain type. In each participant with diabetes, we assessed glycaemic control by taking the mean of all the HbA1cmeasurements from 3 years before study entry to 3 years after, ignoring values occurring after an endpoint.

For continuous variables (BMI, HDL cholesterol, total cholesterol, and systolic blood pressure) we used, as a baseline value, the most recent measurement recorded in CPRD in the year before study entry, but included measurements outside this time window in imputation models. Social deprivation was included in models as quintiles of the index of multiple deprivation,a score calculated for each participant's neighbourhood on the basis of social indices such as income, education, and employment. Data recorded before study entry were used to classify participants as never smokers, ex-smokers, or current smokers at baseline.Outcomes The primary endpoint was the first record of one of the following 12 cardiovascular presentations in any of the data sources: stable angina, unstable angina, myocardial infarction, unheralded coronary death, heart failure, transient ischaemic attack, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, peripheral arterial disease, abdominal aortic aneurysm, and a composite outcome classified as arrhythmia or sudden cardiac death, which consisted of cardioversion, ventricular arrhythmia, implantable cardioverter defibrillator, cardiac arrest, or sudden cardiac death. Any events occurring after the first cardiovascular presentation were ignored. Endpoint definitions are described in the appendix and coding algorithms are available .Secondary outcomes were cardiovascular mortality and all-cause mortality

Results

The study cohort included 50 individuals, of whom 35 had cardiac disease with diabetes and 15 did not have cardiac disease in type 2 diabetes. People with type 2 diabetes had lower mean HDL cholesterol and higher mean BMI than people without diabetes ). The use of statins and antihypertensive medication was greater in people with type 2 diabetes than in those without diabetes, and increased over time .People with type 2 diabetes were about twice as likely to be black or south Asian as those without diabetes

Women without

cardiac disease in type 2 DM

Women with cardiac

disease in Type 2DM

Men without cardiac

disease in type 2 DM

Men with cardiac disease

in type 2 DM

Age/years 3.6 (16.2) 3.5 (14.4) 2.6 (17.6) 5.8 (18.3)

Current smoker 2.5 (17.6) 4(14.8) 4 (23.7) 6 (20.6)

No smoker 8 (67.9) 18(64.9) 8.3 (58.7) 16 (45.3)

Systolic pressure 3.8 (19.6) 7 (19.7) 2.7 (17.2) 5 (17.6)

Diastolic pressure 1.5 (10.3) 3.5 (14.4) 1 (10%) 3.5 (14.8)

Total cholesterol 2.6 (16.2) 8 (23.4) 3.6 (19.2) 7.3 (23.4)

HDL concentration 3.2(10.2) 6 (18.5) 1.7 (10.3) 18 (50.3)

Random glucose level

1 (10) 5 (15.5) 7.5 (67.9) 4.7 (16.4)

Fasting glucose level

4(20) 2.5 (10) 4.8 (27.5) 8 (25.1)

CONCLUSIONSIndividuals with type 1 and type 2 diabetes carry an increased risk of vascular and myocardial disease. These complications contribute significantly to morbidity and mortality among those living with diabetes. While a number of therapeutic approaches have improved outcomes in both CAD and heart failure in diabetes, more remains to be understood regarding the links between the altered metabolic state in diabetes and the cardiovascular pathology with which it is associated. Such new knowledge will enable development of more effective therapies that are specifically aimed at the underlying causes of the cardiovascular complications in diabetics.

Management

Despite advances in medical therapy of diabetes, diabetic patients with coronary disease fare poorly when compared to those without diabetes. This may reflect, in part, the observation that diabetics more frequently have silent ischemia related to autonomic dysfunction, such that they present later in the course of this chronic disease [28]. It also likely reflects the incomplete normalization of the absolute levels and the dynamic excursions of insulin, glucose and fatty acids despite aggressive diabetic management. Furthermore, while increased insulin levels and hyperglycemia generally predict adverse outcomes in diabetic patients [29], tight glycemic control, though seemingly logical, has been controversial with regard to decreasing macrovascular complications, such as CAD. Most recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial found that independent of hypoglycemic events, type 2 diabetic subjects randomized to tight glycemic therapy had increased mortality, prompting early termination of the study [30, 31]. On the other hand, the lack of significant cardiovascular benefits in this trial must be weighed with the clear benefits of aggressive glycemic targets for decreasing microvascular disease, particularly in type 1 diabetes.

Controlling non-glycemic risk factors is also extremely important for treating CAD in the diabetic patient and is strongly recommended by both the American Diabetic Association and the American Heart Association [32]. Benefits have been noted with tobacco cessation and healthy lifestyle choices including exercise and weight reduction [33]. Multiple trials have shown decreased cardiovascular events in diabetic patients with aggressive lipid lowering using statin drugs [33-37]. Likewise, vigorous control of blood pressure decreases cardiovascular event rates. While most anti-hypertensive agents are effective in this regard, antagonism of the renin-angiotensin-aldosterone axis is particularly important in diabetic patients to decrease myocardial infarction and death, with data supporting the use of angiotensin converting enzyme inhibitors (ACE-I) from the Heart Outcomes Prevention Evaluation (HOPE) trial and the micro HOPE substudy, and the use of angiotensin receptor blockers

(ARBs) from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial [38, 39].

A number of multicenter trials have examined outcomes in diabetics with CAD following revascularization. Subgroup analysis from the Bypass Angioplasty Revascularization Investigation (BARI) study showed that coronary artery bypass grafting (CABG) in diabetics, who presented with acute coronary syndromes due to multivessel CAD, improved long-term survival better than PCI [40]. This survival benefit was most apparent among those receiving at least one arterial graft as opposed to those receiving only vein grafts. Subsequently, a number of studies have compared treatment modalities in diabetics with stable ischemic heart disease. The BARI 2D study showed that in diabetics with stable but more severe CAD (affecting all three coronary vessels), prompt revascularization by CABG compared to medical therapy conferred a reduction in major cardiovascular events. Initial results from the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial also showed a benefit of CABG over drug-eluting stents in terms of decreased adverse cardiac events in CABG-treated patients and increased need for revascularization among those receiving drug eluting stents [41]. In diabetics with stable and less severe CAD, intensive medical therapy was as effective as PCI as a first-line therapy in BARI 2D [42]. Important additional data is expected to come from the ongoing Future Revascularization Evaluation in patients with Diabetes Mellitus: Optimal Management of Multivessel disease (FREEDOM) study that will evaluate CABG versus PCI in a study design that incorporates the most advanced approaches to PCI and optimal medical management

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