Metabolic Syndrome and Risk of Incident Cardiovascular Events and Death
Metabolic Syndrome and Risk of Incident Cardiovascular Events and Death
Objectives: The purpose of this research was to assess the association between the metabolic syndrome (MetSyn) and cardiovascular events and mortality by meta-analyses of longitudinal studies.
Background: Controversy exists regarding the cardiovascular risk associated with MetSyn.
Methods: We searched electronic reference databases through March 2005, studies that referenced Reaven's seminal article, abstracts presented at meetings in 2003 to 2004, and queried experts. Two reviewers independently assessed eligibility. Longitudinal studies reporting associations between MetSyn and cardiovascular events or mortality were eligible. Two reviewers independently used a standardized form to collect data from published reports. Authors were contacted. Study quality was assessed by the control of selection, detection, and attrition biases.
Results: We found 37 eligible studies that included 43 cohorts (inception 1971 to 1997) and 172,573 individuals. Random effects meta-analyses showed MetSyn had a relative risk (RR) of cardiovascular events and death of 1.78 (95% confidence interval [CI] 1.58 to 2.00). The association was stronger in women (RR2.63 vs. 1.98, p=0.09), in studies enrolling lower risk (<10%) individuals (RR1.96 vs. 1.43, p=0.04), and in studies using factor analysis or the World Health Organization definition (RR2.68 and 2.06 vs. 1.67 for National Cholesterol Education Program definition and 1.35 for other definitions; p=0.005).The association remained after adjusting for traditional cardiovascular risk factors (RR1.54, 95% CI 1.32 to 1.79).
Conclusions: The best available evidence suggests that people with MetSyn are at increased risk of cardiovascular events. These results can help clinicians counsel patients to consider lifestyle interventions, and should fuel research of other preventive interventions. (J Am Coll Cardiol 2007;49:403-14) © 2007 by the American College of Cardiology Foundation
The metabolic syndrome (MetSyn), also termed the insulin resistance syndrome, is the concurrence in an individual of multiple metabolic abnormalities associated with cardiovascular disease. Cross-sectional surveys indicate that, in the U.S., one-third of adults and an alarming proportion of children have the MetSyn. It represents a global public health problem. Since 1988, when Reaven first systematically described it, an abundance of research has advanced an understanding of the pathophysiology, epidemiology, prognostic implications, and therapeutic strategies related to the MetSyn. Despite this progress, fundamental uncertainties persist regarding the MetSyn, as highlighted by recent national and international diabetes organizations' doubt regarding even its existence.
Reaven's first definition of the MetSyn included these components: hyperglycemia, abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol concentration, and hypertension. Its pathogenesis, unified by the putative mechanism of insulin resistance, was thought to be related to interactions between sedentary lifestyle, diet, and genetic factors. In 1998, the American Diabetes Association proposed that MetSyn is comprised of glucose intolerance, central obesity, dyslipidemia (including increased triglycerides, decreased high-density lipoprotein cholesterol concentration, and increased small dense low-density lipoprotein cholesterol concentration), hypertension, increased prothrombotic and antifibrinolytic factors, and risk for atherosclerotic disease; but, it did not propose specific definitions or thresholds for these processes. In 1999, the World Health Organization (WHO) codified specific components and thresholds for the MetSyn and in 2003 the U.S. National Cholesterol Education Program (NCEP) redefined the MetSyn in an attempt to simplify the clinical application of its criteria and improve its recognition. Despite these efforts, there exists no genuine consensus of the unique components that comprise the MetSyn. Burgeoning information regarding its pathophysiology adds to the uncertainty.
Only recently have there been studies assessing the risk of incident cardiovascular disease events attributable to the MetSyn. These studies had different populations, definitions of MetSyn, methods, and results. Because of this variability and the current controversy regarding its implications, we propose that a systematic review and metaanalysis of the existing data will provide the current best evidence. In addition to providing an overall estimate of risk, the tools of meta-analysis allow an evaluation of differences between studies that could clarify the prognostic implications of how MetSyn is defined, in which settings it may be informative, and other issues related to its clinical use.
We performed a meta-analysis of longitudinal studies that assessed any cardiovascular event outcomes or mortality in people with clustering of 3 or more coronary risk factors (regardless of whether this was termed the MetSyn) compared with people without that phenotype. We expected to capitalize on the high heterogeneity between studies to identify likely explanations for it in factors related to population characteristics, outcome and exposure ascertainment, and study quality. The reporting of this systematic review follows current standards.
Objectives: The purpose of this research was to assess the association between the metabolic syndrome (MetSyn) and cardiovascular events and mortality by meta-analyses of longitudinal studies.
Background: Controversy exists regarding the cardiovascular risk associated with MetSyn.
Methods: We searched electronic reference databases through March 2005, studies that referenced Reaven's seminal article, abstracts presented at meetings in 2003 to 2004, and queried experts. Two reviewers independently assessed eligibility. Longitudinal studies reporting associations between MetSyn and cardiovascular events or mortality were eligible. Two reviewers independently used a standardized form to collect data from published reports. Authors were contacted. Study quality was assessed by the control of selection, detection, and attrition biases.
Results: We found 37 eligible studies that included 43 cohorts (inception 1971 to 1997) and 172,573 individuals. Random effects meta-analyses showed MetSyn had a relative risk (RR) of cardiovascular events and death of 1.78 (95% confidence interval [CI] 1.58 to 2.00). The association was stronger in women (RR2.63 vs. 1.98, p=0.09), in studies enrolling lower risk (<10%) individuals (RR1.96 vs. 1.43, p=0.04), and in studies using factor analysis or the World Health Organization definition (RR2.68 and 2.06 vs. 1.67 for National Cholesterol Education Program definition and 1.35 for other definitions; p=0.005).The association remained after adjusting for traditional cardiovascular risk factors (RR1.54, 95% CI 1.32 to 1.79).
Conclusions: The best available evidence suggests that people with MetSyn are at increased risk of cardiovascular events. These results can help clinicians counsel patients to consider lifestyle interventions, and should fuel research of other preventive interventions. (J Am Coll Cardiol 2007;49:403-14) © 2007 by the American College of Cardiology Foundation
The metabolic syndrome (MetSyn), also termed the insulin resistance syndrome, is the concurrence in an individual of multiple metabolic abnormalities associated with cardiovascular disease. Cross-sectional surveys indicate that, in the U.S., one-third of adults and an alarming proportion of children have the MetSyn. It represents a global public health problem. Since 1988, when Reaven first systematically described it, an abundance of research has advanced an understanding of the pathophysiology, epidemiology, prognostic implications, and therapeutic strategies related to the MetSyn. Despite this progress, fundamental uncertainties persist regarding the MetSyn, as highlighted by recent national and international diabetes organizations' doubt regarding even its existence.
Reaven's first definition of the MetSyn included these components: hyperglycemia, abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol concentration, and hypertension. Its pathogenesis, unified by the putative mechanism of insulin resistance, was thought to be related to interactions between sedentary lifestyle, diet, and genetic factors. In 1998, the American Diabetes Association proposed that MetSyn is comprised of glucose intolerance, central obesity, dyslipidemia (including increased triglycerides, decreased high-density lipoprotein cholesterol concentration, and increased small dense low-density lipoprotein cholesterol concentration), hypertension, increased prothrombotic and antifibrinolytic factors, and risk for atherosclerotic disease; but, it did not propose specific definitions or thresholds for these processes. In 1999, the World Health Organization (WHO) codified specific components and thresholds for the MetSyn and in 2003 the U.S. National Cholesterol Education Program (NCEP) redefined the MetSyn in an attempt to simplify the clinical application of its criteria and improve its recognition. Despite these efforts, there exists no genuine consensus of the unique components that comprise the MetSyn. Burgeoning information regarding its pathophysiology adds to the uncertainty.
Only recently have there been studies assessing the risk of incident cardiovascular disease events attributable to the MetSyn. These studies had different populations, definitions of MetSyn, methods, and results. Because of this variability and the current controversy regarding its implications, we propose that a systematic review and metaanalysis of the existing data will provide the current best evidence. In addition to providing an overall estimate of risk, the tools of meta-analysis allow an evaluation of differences between studies that could clarify the prognostic implications of how MetSyn is defined, in which settings it may be informative, and other issues related to its clinical use.
We performed a meta-analysis of longitudinal studies that assessed any cardiovascular event outcomes or mortality in people with clustering of 3 or more coronary risk factors (regardless of whether this was termed the MetSyn) compared with people without that phenotype. We expected to capitalize on the high heterogeneity between studies to identify likely explanations for it in factors related to population characteristics, outcome and exposure ascertainment, and study quality. The reporting of this systematic review follows current standards.
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