流行和临床症状不显的心血管疾病的预断冲击在个体以新陈代谢的综合症状和糖尿病.docx

1、流行和临床症状不显的心血管疾病的预断冲击在个体以新陈代谢的综合症状和糖尿病Prevalence and Prognostic Impact of Subclinical Cardiovascular Disease in Individuals With the Metabolic Syndrome and DiabetesErik Ingelsson1, Lisa M. Sullivan2, Joanne M. Murabito1,3, Caroline S. Fox1,4, Emelia J. Benjamin1,5,6, Joseph F. Polak7, James B. Meigs8

2、, Michelle J. Keyes1,9, Christopher J. ODonnell1,10,11, Thomas J. Wang1,10, Ralph B. DAgostino, Sr.1,9, Philip A. Wolf1,12, and Ramachandran S. Vasan1,5,6 1 National Heart, Lung, and Blood Institutes Framingham Study, Framingham, Massachusetts2 Department of Biostatistics, Boston University, Boston,

3、 Massachusetts3 Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts4 Division of Endocrinology, Diabetes, and Hypertension, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts5 Department of Preventive Medicine, Boston University S

4、chool of Medicine, Boston, Massachusetts6 Cardiology Section, Boston University School of Medicine, Boston, Massachusetts7 New England Medical Center, Tufts University, Boston, Massachusetts8 General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School

5、, Boston, Massachusetts9 Department of Mathematics and Statistics, Boston University, Boston, Massachusetts10 Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts11 National Heart, Lung, and Blood Institute, Center for Population Studies, Bethesda, Ma

6、ryland12 Departments of Neurology and Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts Address correspondence and reprint requests to Ramachandran S. Vasan, MD, FACC, Framingham Heart Study, 73 Mount Wayte Ave., Suite 2, Framingham, MA 01702-5803. E-m

7、ail: vasanbu.edu Abbreviations: CVD, cardiovascular disease; IMT, intima-media thickness; LVH, left ventricular hypertrophy; MetS, metabolic syndrome ABSTRACT TOPABSTRACTRESEARCH DESIGN AND METHODSRESULTSDISCUSSIONREFERENCESData are limited regarding prevalence and prognostic significance of subclin

8、ical cardiovascular disease (CVD) in individuals with metabolic syndrome (MetS). We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressur

9、e, and urinary albumin excretion. We prospectively evaluated the incidence of CVD associated with MetS and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with MetS had subclinical disease in at least one test, a frequency higher than

10、individuals without MetS (multivariable-adjusted odds ratio 2.06 95% CI 1.672.55; P 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with MetS (10.2%). Overall, MetS was associated with increased CVD risk (multivariable-adjusted hazards ratio HR 1.61 95% CI 1

11、.122.33). Participants with MetS and subclinical disease experienced increased risk of overt CVD (2.67 1.624.41 compared with those without MetS, diabetes, or subclinical disease), whereas the association of MetS with CVD risk was attenuated in absence of subclinical disease (HR 1.59 95% CI 0.872.90

12、). A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without MetS or diabetes (1.93 1.153.24). In our community-based sample, individuals with MetS have a high prevalence of

13、 subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition. Presence of subclinical disease in multiple vascular beds has been suggested as an indicator of overall atherosclerotic burden (1). Consistent with this concept, investigators have

14、reported an increased risk of overt cardiovascular disease (CVD) events in individuals with subclinical disease (24) or target organ damage (as evidenced by left ventricular hypertrophy LVH 5,6 or microalbuminuria 79). It is also widely acknowledged that established risk factors for overt CVD promot

15、e the development of subclinical CVD (10). In this context, the metabolic syndrome (MetS) is a condition that is associated with the clustering of risk factors including high blood pressure, abdominal obesity, glucose intolerance, and dyslipidemia. Whereas the definition and clinical utility of MetS

16、 has been the subject of recent debate (11,12), it is accepted that MetS carries an increased risk of CVD (13,14). Given the clustering of risk factors that characterizes MetS, it is likely that individuals with MetS have a high burden of subclinical disease (a term used herein to refer to both subc

17、linical atherosclerosis and target organ damage). It is also likely that subclinical disease would contribute to the increased risk of CVD associated with MetS. Yet, data examining this premise comprehensively are lacking in the published literature. Of note, whereas several studies (1525) have docu

18、mented the increased prevalence of subclinical disease in MetS, they have not investigated the potential role of such disease in mediating the vascular risk associated with the condition. Additionally, previous studies (1525) assessing subclinical disease in MetS have typically focused on single mea

19、sures of subclinical disease. Accordingly, we characterized comprehensively the cross-sectional prevalence of subclinical disease in individuals with prevalent MetS in the community. Additionally, we tested the hypothesis that the presence of subclinical disease contributes to the increased risk of

20、overt CVD associated with MetS prospectively. RESEARCH DESIGN AND METHODS TOPABSTRACTRESEARCH DESIGN AND METHODSRESULTSDISCUSSIONREFERENCESThe design and selection criteria of the Framingham Offspring Study have been described previously (26). Participants who attended the sixth examination cycle (1

21、9951998) were eligible for the present study (n = 3,532). The participants underwent routine medical history, physical examination including blood pressure measurement, anthropometry, laboratory assessment of CVD risk factors, and testing for the presence of subclinical CVD (see section below). The

22、institutional review board at Boston Medical Center approved the study, and all participants gave written informed consent. Participants were excluded from the present investigation for the following reasons: prevalent CVD at baseline (n = 415), unavailable electrocardiography data (n = 6), unavaila

23、ble measurement of urinary albumin (n = 460), unavailable ankle-brachial blood pressure data (n = 49), unavailable or inadequate carotid ultrasonography data (n = 70), and unavailable or inadequate echocardiographic left ventricular mass data (n = 587). After these exclusions, 1,945 individuals (mea

24、n age 58 years; 59% women) were eligible and constituted the study sample. Definition of risk factors and MetS.Cigarette smoking was defined by self-report of cigarette use within the year preceding the heart study baseline examination. Diabetes was defined as a fasting plasma glucose 126 mg/dl or u

25、se of insulin or oral hypoglycemic agents (27). The MetS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria (28) by the presence of three or more of the following: increased waist circumference (102 cm for men, 88 cm for women), elevated b

26、lood pressure (130 mmHg systolic or 85 mmHg diastolic or treatment for hypertension), hyperglycemia (fasting blood glucose 100 mg/dl or treatment for elevated glucose), hypertriglyceridemia (150 mg/dl or treatment with nicotinic acid or fibrates), or low HDL cholesterol (40 mg/dl in men, 50 mg/dl in

27、 women). Subclinical disease measures and score.Measures of subclinical vascular disease and target organ damage were chosen based on a review of the published literature. The five tests used to characterize the prevalence of subclinical disease are detailed in Table 1 and described briefly below. A

28、 standard 12-lead computerized resting electrocardiogram was obtained with the participants in a supine position. The sex-specific Cornell voltage criteria were used to assess the presence of electrocardiographic LVH (29). All participants underwent routine transthoracic echocardiographic examinatio

29、n. M-mode measurements of left ventricular dimensions were obtained by the leading-edge-to-leading-edge technique (30). Left ventricular ejection fraction was estimated by experienced observers based on the visual assessment of left ventricular contractile performance and wall motion in multiple two

30、-dimensional views. Carotid ultrasound readings were acquired and images analyzed according to a standard protocol (31). Imaging was conducted using a high-resolution 7.5-MHz transducer for the common carotid artery and a 5.0-MHz transducer for the carotid bulb and internal carotid artery (Toshiba M

31、edical Systems), as described previously (32). Carotid intima-media thickness (IMT) measurements were made from gated diastolic images of the left and right carotid artery at the level of the distal common carotid artery, the carotid artery bulb, and the proximal 2 cm of the internal carotid artery.

32、 The maximal IMT at each site was defined as the mean of the maximal IMT measured at the near and far walls of the vessel. The internal carotid artery IMT was defined as the mean of the maximal IMT measurements for the carotid artery bulb and the internal carotid artery on both the right and left side. Ankle-brachial systolic blood pressure measurements were obtained by trained technicians according to a standard protocol, using an 8-MHz Doppler pen probe and an ultrasonic Doppler flow detector