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Diabetic Cardiomyopathy and Subclinical Cardiovascular Disease the Multi-Ethnic Study of Atherosclerosis (MESA)

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Diabetic Cardiomyopathy and Subclinical Cardiovascular Disease the Multi-Ethnic Study of Atherosclerosis (MESA) Pathophysiology/Complications ORIGINAL ARTICLE Diabetic Cardiomyopathy and Subclinical Cardiovascular Disease The Multi-Ethnic Study of Atherosclerosis (MESA) 1 4 ALAIN G. BERTONI, MD, MPH JOSEPH F. POLAK, MD, MPH eart failure has become a frequent 1 5 DAVID C. GOFF,JR., MD, PHD MOHAMMED F. SAAD, MD, MRCP manifestation of cardiovascular dis- 1 6 RALPH B. D’AGOSTINO,JR., PHD MOYSES SZKLO, MD, DRPH 2 ease (CVD) among individuals with IANG IU PHD 7 H K L , RUSSELL P. TRACY, PHD diabetes (1). As the prevalence of diabetes 1 8 W. GREGORY HUNDLEY, MD AVID ISCOVICK MD, MPH 3 D S. S , increases, it will probably emerge as one JOAO A. LIMA, MD of the principal causes of heart failure in the U.S. (2–4). There is significant evi- dence of the existence of “diabetic cardio- OBJECTIVE — Studies have demonstrated increased left ventricular mass (LVM) and dia- myopathy,” described classically as heart stolic dysfunction among diabetic patients without clinical cardiovascular disease (CVD), but failure in the absence of obstructive coro- few have assessed the potential contribution of subclinical CVD to ventricular abnormalities in nary disease but now more often defining diabetes. We examined whether diabetic cardiomyopathy is associated with subclinical athero- sclerosis and if abnormalities are found with impaired fasting glucose (IFG). ventricular abnormalities seen in individ- uals without coronary disease including RESEARCH DESIGN AND METHODS — LVM, end-diastolic volume (EDV), and increased left ventricular mass (LVM) and stroke volume were measured by magnetic resonance imaging (MRI), and atherosclerosis was impaired diastolic function (3,5–8). Pro- assessed by coronary artery calcium and carotid intima-media wall thickness in 4,991 partici- posed mechanisms include deleterious ef- pants in the Multi-Ethnic Study of Atherosclerosis, a cohort study of adults aged 45–84 without fects of hyperglycemia, hypertension, and prior CVD. Multivariable linear regression was used to analyze the association between MRI impaired endothelial function, which measures and glucose status. may lead to compromised myocardial blood flow (8,9). Atherosclerosis may be a RESULTS — Increased LVM was observed in white, black, and Hispanic participants with contributing factor in diabetic cardiomy- diabetes but not among Chinese participants. After adjustment for weight, height, CVD risk factors, and subclinical atherosclerosis, ethnicity-specific differences in ventricular parameters opathy, as many studies have not had an- were present. Among whites and Chinese with diabetes, LVM was similar to that in normal giographic data or have focused on the subjects; EDV and stroke volume were reduced. In blacks with diabetes, EDV and stroke volume lack of obstructive lesions on coronary were reduced, and LVM was increased (ϩ5.6 g, P Ͻ 0.05). Among Hispanics with diabetes, EDV angiography and have not determined the and stroke volume were similar to normal, but LVM was increased (ϩ5.5 g, P Ͻ 0.05). After presence or extent of subclinical CVD. adjustment, IFG was associated with a decrease in EDV and stroke volume in whites and blacks There is less information available on only; however, no significant differences in LVM were observed. whether cardiomyopathy is also present in impaired fasting glucose (IFG), al- CONCLUSIONS — Ethnicity-specific differences in LVM, EDV, and stroke volume are as- though an association between IFG sociated with abnormal glucose metabolism and are independent of subclinical CVD. and heart failure has been found (10). Diabetes Care 29:588–594, 2006 Determining the relationship between subclinical atherosclerosis and early ab- normalities in diabetic and pre-diabetic ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● hearts would advance our understanding of the pathophysiology of ventricular dys- From the 1Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina; the 2Department of Preventive Medicine, Northwestern University, Chicago, Illinois; the function and may suggest interventions to 3Department of Medicine, Johns Hopkins University, Baltimore, Maryland; the 4Department of Radiology, prevent heart failure in at-risk adults. Tufts-New England Medical Center, Boston, Massachusetts; the 5Department of Preventive Medicine, Health Therefore, we sought to investigate Sciences Center School of Medicine, Stony Brook, New York; the 5Department of Preventive Medicine, whether ventricular abnormalities related 6 Health Sciences Center School of Medicine, Stony Brook, New York; the Department of Epidemiology, to diabetes are also observed in IFG and Johns Hopkins University, Baltimore, Maryland; the 7Department of Pathology, University of Vermont, Colchester, Vermont; and the 8Cardiovascular Health Research Unit, University of Washington, Seattle, whether these abnormalities may be me- Washington. diated by atherosclerosis in the Multi- Address correspondence and reprint requests to Dr. Alain G. Bertoni, Wake Forest University Health Ethnic Study of Atherosclerosis (MESA), a Sciences, Department of Public Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157. population-based cohort of adults with- E-mail: [email protected]. Received for publication 11 August 2005 and accepted in revised form 2 December 2005. out CVD. Abbreviations: CAC, coronary artery calcium; CVD, cardiovascular disease; EDV, end-diastolic volume; ESV, end-systolic volume; IFG, impaired fasting glucose; IMT, intima-media thickness; LVM, left ventricular mass; MESA, Multi-Ethnic Study of Atherosclerosis; MRI, magnetic resonance imaging; NFG, normal fasting RESEARCH DESIGN AND glucose. METHODS — MESA is a population- A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion based sample of 6,814 men and women factors for many substances. from four ethnic groups (white, African © 2006 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby American, Hispanic, and Chinese) aged marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 45–84 without clinical CVD before re- 588 DIABETES CARE, VOLUME 29, NUMBER 3, MARCH 2006 Bertoni and Associates cruitment. Details regarding the design (MRI) was performed using 1.5-Telsa by glucose status were then assessed using and objectives of MESA have been pub- magnets at each center; the MESA proto- multivariable linear regression, with ad- lished (11). Individuals with a medical col has been described in detail (11,13). justment for age, sex, race, clinic, weight, history of heart attack, angina, coronary Briefly, imaging was performed with a and height (model 1). Using interaction revascularization, pacemaker or defibril- four-element, phased-array surface coil terms in these models, we found evidence lator implantation, valve replacement, placed anteriorly and posteriorly, electro- of a significant interaction between glu- heart failure, or cerebrovascular disease cardiogram gating, and brachial artery cose status and ethnicity for several ven- were excluded from the sample. During blood pressure monitoring. Cine images tricular parameters; in ethnicity-stratified the baseline examination (2000–2002), of the left ventricle were obtained during models, we then assessed for a glucose standardized questionnaires and cali- short breath-holding (12–15 s) at resting status–sex interaction. Because of the brated devices were used to obtain demo- lung volume. Quantitative measurements greater evidence for glucose status– graphic data, tobacco usage, medical were performed at one reading center us- ethnicity interaction, further analyses conditions, current prescription medica- ing MASS (v4.2) analytical software for were performed, stratified by ethnicity tion usage, weight, and height. Resting reader interpretation (Medis, Leiden, the and adjusting for sex. Subsequent models seated blood pressure was measured three Netherlands) by one of two trained tech- incorporated risk factors for atherosclero- times using a Dinamap automated oscil- nicians. Left ventricular wall thickness sis (smoking, hypertension, blood pres- lometric sphygmomanometer (model Pro was defined as the average of six midven- sure, LDL and HDL cholesterol, and 100; Critikon, Tampa, FL); the last two tricle segment thickness measurements. triglycerides) and then CAC and carotid measurements were averaged for analysis. Left ventricular EDV and end-systolic vol- IMT to determine whether adjustment for Fasting blood glucose and lipids were an- ume (ESV) were calculated by summing these variables altered the relationship be- alyzed at a central laboratory. Individuals the areas on each separate slice multiplied tween glucose category and ventricular were considered to have diabetes if they by the sum of the slice thickness. End- parameters. We modeled CAC in several replied “Yes” to the question “Has a doctor diastolic LVM was determined by the sum ways, including using the Agatston score ever told you that you had diabetes?” of the area between the epicardial and en- as a continuous variable, as a categorical and/or the medication inventory included docardial contours multiplied by the slice variable (CAC present or not), and as hypoglycemic drugs or if fasting blood thickness; this value was then multiplied quartiles. Because of the large number of glucose was Ն7.0 mmol/l (126 mg/dl). by the specific gravity of myocardium individuals
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