Development and validation of a risk score for hospitalization for heart failure in patients with Type 2 Diabetes Mellitus

<p>Abstract</p> <p>Background</p> <p>There are no risk scores available for predicting heart failure in Type 2 diabetes mellitus (T2DM). Based on the Hong Kong Diabetes Registry, this study aimed to develop and validate a risk score for predicting heart failure that needs hospitalisation in T2DM.</p> <p>Methods</p> <p>7067 Hong Kong Chinese diabetes patients without history of heart failure, and without history and clinical evidence of coronary heart disease at baseline were analyzed. The subjects have been followed up for a median period of 5.5 years. Data were randomly and evenly assigned to a training dataset and a test dataset. Sex-stratified Cox proportional hazard regression was used to obtain predictors of HF-related hospitalization in the training dataset. Calibration was assessed using Hosmer-Lemeshow test and discrimination was examined using the area under receiver's operating characteristic curve (aROC) in the test dataset.</p> <p>Results</p> <p>During the follow-up, 274 patients developed heart failure event/s that needed hospitalisation. Age, body mass index (BMI), spot urinary albumin to creatinine ratio (ACR), HbA_1c, blood haemoglobin (Hb) at baseline and coronary heart disease during follow-up were predictors of HF-related hospitalization in the training dataset. HF-related hospitalization risk score = 0.0709 × age (year) + 0.0627 × BMI (kg/m²) + 0.1363 × HbA_1c(%) + 0.9915 × Log₁₀(1+ACR) (mg/mmol) - 0.3606 × Blood Hb(g/dL) + 0.8161 × CHD during follow-up (1 if yes). The 5-year probability of heart failure = 1-S₀(5)^{EXP{0.9744 × (Risk Score - 2.3961)}}. Where S₀(5) = 0.9888 if male and 0.9809 if female. The predicted and observed 5-year probabilities of HF-related hospitalization were similar (p > 0.20) and the adjusted aROC was 0.920 for 5 years of follow-up.</p> <p>Conclusion</p> <p>The risk score had adequate performance. Further validations in other cohorts of patients with T2DM are needed before clinical use.</p

A Man with Labile Blood Pressure

Ronald Ma and colleagues discuss the differential diagnosis and management of a patient who presented with recurrent episodes of chest discomfort, palpitations, and labile blood pressure

Acute Encephalopathy Associated with Influenza A Infection in Adults

We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios >3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis

Impacts of chronic kidney disease and albuminuria on associations between coronary heart disease and its traditional risk factors in type 2 diabetic patients – the Hong Kong diabetes registry

<p>Abstract</p> <p>Background</p> <p>Glycated haemoglobin (HbA_1c), blood pressure and body mass index (BMI) are risk factors for albuminuria, the latter in turn can lead to hyperlipidaemia. We used novel statistical analyses to examine how albuminuria and chronic kidney disease (CKD) may influence the effects of other risk factors on coronary heart disease (CHD).</p> <p>Methods</p> <p>A prospective cohort of 7067 Chinese type 2 diabetic patients without history of CHD enrolled since 1995 were censored on July 30^th, 2005. Cox proportional hazard regression with restricted cubic spline was used to auto-select predictors. Hazard ratio plots were used to examine the risk of CHD. Based on these plots, non-linear risk factors were categorised and the categorised variables were refitted into various Cox models in a stepwise manner to confirm the findings.</p> <p>Results</p> <p>Age, male gender, duration of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular filtration rate, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and current smoking status were risk factors of CHD. Linear association between TC and CHD was observed only in patients with albuminuria. Although in general, increased HDL-C was associated with decreased risk of CHD, full-range HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L. Albuminuria and CKD were the main contributors for the paradoxically positive association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L.</p> <p>Conclusion</p> <p>In type 2 diabetes, albuminuria plays a linking role between conventional risk factors and CHD. The onset of CKD changes risk associations between lipids and CHD.</p

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The Case: A 62-year-old woman had been admitted to hospital in July 1992 with flu-like symptoms and malaise. At that time, she had a 5-year history of hypertension and newly diagnosed diabetes mellitus. She denied having chest pain and had no pertinent family history. An electrocardiogram (ECG) obtained on admission showed STsegment depression over leads V 1 through V 4 and nonpathological Q waves over V 4 through V 6 . After admission, shock developed that required inotropic support, and treatment for a suspected non-ST-segment elevation myocardial infarction (MI) was started. This diagnosis was supported by serial cardiac enzyme levels: peak creatine kinase 592 (normal &lt; 235) U/L and lactate dehydrogenase 383 (normal &lt; 246) U/L. Echocardiography revealed left ventricular hypertrophy (LVH) and mild hypokinesia. Cardiac catheterization revealed concentric LVH, but normal coronary arteries. The patient was discharged a few days later, was well on follow-up and had no chest pain. Four years later, the patient was admitted to hospital with vomiting, dizziness and chest pain. She was hypotensive on admission. An ECG showed ST-segment elevation over leads V 2 through V 5 Over the next 12 months, the patient was admitted on 2 other occasions because of chest discomfort and dizziness. Her cardiac enzyme levels were elevated, and an ECG showed changes on both occasions; therefore, treatment for acute coronary syndromes was started. Recurrent syncopal episodes with documented postural hypotension also developed. Warfarin therapy was stopped in August 1997 following an echocardiogram that showed no further evidence of atrial thrombus. A repeat echocardiogram in September 1997 showed marked septal left ventricular hypertrophy with a mild subaortic gradient, systolic anterior movement of the mitral valve and midsystolic closure of the aortic valve with mild mitral valve regurgitation, which suggested hypertrophic obstructive cardiomyopathy (see video 1, available online at www.cmaj.ca/cgi/content/full /176/2/171-a/DC1). At a follow-up visit in March 1998 the patient described persistent dizzy spells and occasional headaches. She was noted to have suboptimal blood pressure control. A 24-hour urine collection for catecholamines was performed, which revealed marked elevation of catecholamine levels: epinephrine 1239 (normal 19-113) nmol/d and norepinephrine 1743 (normal 63-416) nmol/d. A CT scan revealed a 4-cm lesion on the left adrenal gland The patient we described presented with recurrent episodes of chest pain and vomiting as well as ECG changes suggestive of cardiac ischemia. Subsequent investigations, including coronary angiography, did not show evidence of substantial coronary artery disease. The patient also had marked LVH resembling hypertrophic obstructive cardiomyopathy. These cardiac complications were later found to be caused by a pheochromoctyoma. Pheochromocytoma can present with a myriad of symptoms (Box 1). This diagnosis is often not suspected, and at least 35% of pheochromocytomas are diagnosed at autopsy. If the classic symptoms of sweating, palpitations and headache are absent, as in the case we have described, it could be difficult to diagnose. Our patient was likely to have harboured the pheochromocytoma at the time of her first admission in 1992, because her long history of hypertension and diabetes was resolved after removal of the tumour. Although patients with pheochromocytoma typically describe paroxysms, there is marked variability in its manifestations between patients that can be attributed to the effects of catecholamines. Most patients with pheochromocytoma have hypertension, which may be intermittent, remittent or persistent. Paroxysms of severe hypertension occur in about 50% of cases. After an intense and prolonged episode of hypertension, shock may ultimately occur. This may be caused by low plasma volume, arrhythmias, cardiac damage or loss of vascular tone. In addition, epinephrine secretion from a pheochromocytoma, as in the present case, can cause episodic hypotension and syncope. This is attributed to concomitant stimulation of β 2 receptors, which results in vasodilatation in skeletal muscles. Excess catecholamine levels can also precipitate arrhythmias, which were present in about 20% of patients with catecholamine-secreting tumours in one study. 1 Pheochromocytoma can induce myocardial damage in a variety of ways. Long-standing hypertension can cause ventricular hypertrophy and, as in this case, marked septal hypertrophy. Coupled with intravascular volume depletion and impaired diastolic filling, outflow tract obstructions simulating hypertrophic obstructive cardiomyopathy may occur. In such cases, the echocardiographic features have been noted to improve following tumour resection. 2 In addition, persistent and prolonged exposure to high levels of catecholamines can result in dilated cardiomyopathy or catecholamine myocarditis, which is characterized by foci of myocardial cellular necrosis. In rare instances, pheochromocytoma has been reported to mimic an acute myocardial infarction. In these cases, there may be marked ECG changes, including T-wave inversion and STsegment elevation. 3 Catecholamines can alter ion transport across cell membranes and can alter the rate of membrane depolarization, which results in ECG changes that are suggestive of ischemia. In addition, ECG changes may be accompanied by segmental or global myocardial dysfunction, which may lead to pulmonary edema. 4 The pathophysiology of the myocardial dysfunction associated with pheochromocytoma has been linked to a direct toxic effect induced by catecholamines, demand ischemia due to increased • Erythrocytosis • Hyperamylasemia As part of a familial pheochromocytoma syndrome myocardial oxygen consumption, and myocardial stunning caused by coronary spasm. In the present case, the lack of residual contractile dysfunction or ECG abnormalities after acute episodes with ischemic changes and marked left ventricular regional hypokinesia suggested myocardial stunning to be the underlying mechanism. The diagnosis of pheochromocytoma is established by demonstrating excessive levels of catecholamines or their metabolites in blood or urine. It is now recognized that the measurement of free metanephrines in plasma or fractionated metanephrines in urine offers the highest sensitivity and specificity for the diagnosis of a pheochromocytoma. 5 Imaging studies should be arranged to localize the tumour after the demonstration of unequivocal biochemical evidence of a pheochromocytoma. Definitive surgery can often be performed laparoscopically but requires careful preoperative preparation. Preoperative α-blockade can normalize ischemic changes on an ECG due to catecholamine-induced cardiac ischemia. This unusual case illustrates several of the cardiovascular manifestations of pheochromocytoma. Pheochromocytoma should be included in the differential diagnosis of acute coronary syndromes, and clinicians should be aware of the less common presentations of pheochromocytoma in order to diagnose this potentially fatal condition (Box 2). Ronald C.W. M

Lessons from the Severe Acute Respiratory Syndrome Outbreak in Hong Kong

Severe acute respiratory syndrome (SARS) is now a global public health threat with many medical, ethical, social, economic, political, and legal implications. The nonspecific signs and symptoms of this disease, coupled with a relatively long incubation period and the initial absence of a reliable diagnostic test, limited the understanding of the magnitude of the outbreak. This paper outlines our experience with public health issues that have arisen during this outbreak of SARS in Hong Kong. We confirmed that case detection, reporting, clear and timely dissemination of information, and strict infection control measures are essential in handling such an infectious disease outbreak. The need for an outbreak response unit is crucial to combat any future outbreak

PERSPECTIVES Lessons from the Severe Acute Respiratory Syndrome Outbreak in Hong Kong

This paper outlines our experience with public health issues that have arisen during this outbreak of SARS in Hong Kong. We confirmed that case detection, reporting, clear and timely dissemination of information, and strict infection control measures are essential in handling such an infectious disease outbreak. The need for an outbreak response unit is crucial to combat any future outbrea