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1.  The potential impact of family history of metabolic syndrome and risk of type 2 diabetes mellitus: In a highly endogamous population 
This study aims to determine the potential impact of positive family history of Metabolic Syndrome (MetS) among two generations, on developing Type 2 Diabetes Mellitus (T2DM) and the potential relation of consanguineous marriage among patients with MetS to the risk of developing T2DM among a sample of Qataris.
A cross-sectional study.
Primary healthcare (PHC) centers.
Materials and Methods:
The survey and measurement were conducted from April 2011 to December 2012 among Qatari nationals above 20 years of age. Of the 2,182 subjects, who were approached to participate in the study, 1,552 (71%) gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by anthropometric measurements and laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III) as well as International Diabetes Federation (IDF).
Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9% according to IDF (P < 0.0001). The mean age of MetS patients with T2DM was significantly higher than those without T2DM (Mean 48 ± 9.9 vs. 42.5 ± 9.2; P < 0.001). The proportion of females was higher among MetS patients with T2DM as compared to those without T2DM (61% vs. 51%; P = 0.053). In addition, there were significant differences between MetS patients with and without DM in terms of co-morbidities of hypertension, coronary heart disease, and high cholesterol. The proportion of MetS patients with positive family history for MetS was significantly higher in MetS patients with T2DM as compared to those without T2DM (46.7% vs. 33.8%; P = 0.009). The proportion of positive family history of MetS among fathers (35% vs. 21.9%; P = 0.005), mothers (30.5% vs. 18.8%; P = 0.008), maternal aunt (18.3% vs. 11.2%; P = 0.055), and maternal grand father (19.5% vs. 10%; P = 0.010) were significantly higher in MetS patients with T2DM as compared to the counterpart. The proportion of consanguineous marriages was almost two times higher among MetS patients with T2DM as compared to those without T2DM (80.9% vs. 41.9%; P < 0.001). The proportion of MetS patients with T2DM was lower than MetS patients without DM below 45 years, but after 45 years, the proportion of MetS patients with T2DM remained higher than their counterparts.
Family history of MetS among parents, maternal aunt, maternal grandfather, and consanguineous marriages among patients of MetS are significantly associated with the development of T2DM in Qatar. These results support the necessity of earlier screening for T2DM among MetS patients with positive family history of MetS.
PMCID: PMC3987271  PMID: 24741517
Consanguinity; correlates; diabetes mellitus; genetics; metabolic syndrome; prevalence
2.  Prevalence of the metabolic syndrome in patients with carotid disease according to NHLBI/AHA and IDF criteria: a cross-sectional study 
Metabolic syndrome (MetS) has been related to type 2 diabetes and cardiovascular diseases. Different criteria for diagnosis of MetS have been recommended, but there is no agreement about which criteria are best to use. The aim of the present study was to investigate agreement between the National Heart, Lung, and Blood Institute, American Heart Association (NHLBI/AHA) and the International Diabetes Federation (IDF) definitions of MetS in patients with symptomatic carotid disease and to compare the frequency of cardiovascular risk factor in patients with MetS diagnosed by these two sets of criteria.
The study was a cross-sectional one involving 644 consecutive patients with verified carotid disease who referred to the Vascular Surgery Clinic Dedinje in Belgrade during the period April 2006 - November 2007. Anthropometric parameters blood pressure, fasting plasma glucose and lipoproteins were measured using standard procedures.
MetS was present in 67.9% of participants, according to IDF criteria, and in 64.9% of participants, according to the NHLBI/AHA criteria. A total of 119 patients were categorized differently by the two definitions. Out of all participants 10.7% had MetS by IDF criteria only and 7.8% of patients had MetS by NHLBI/AHA criteria only. The overall agreement of IDF and NHLBI/AHA criteria was 81.5% (Kappa 0.59, p < 0.001). In comparison with patients who met only IDF criteria, patients who met only NHLBI/AHA criteria had significantly more frequently cardiovascular risk factors with the exception of obesity which was significantly more frequent in patients with MetS diagnosed by IDF criteria.
The MetS prevalence in patients with symptomatic carotid disease was high regardless of criteria used for its diagnosis. Since some patients with known cardiovascular risk factors were lost by the use of IDF criteria it seems that NHLBI/AHA definition is more suitable for diagnosis of MetS. Large follow-up studies are needed to test prognostic value of these definitions.
PMCID: PMC3306734  PMID: 22292476
metabolic syndrome; carotid disease; risk factors
3.  Characteristics and in-hospital outcomes of patients with acute coronary syndromes and heart failure in the United Arab Emirates 
BMC Research Notes  2012;5:534.
Heart failure (HF) is a serious complication of acute coronary syndromes (ACS), and is associated with high in-hospital mortality and poor long-term survival. The aims of this study were to describe the clinical characteristics, management and in-hospital outcomes of coronary syndrome (ACS) patients with HF in the United Arab Emirates.
The study was selected from the Gulf Registry of Acute Coronary Events (Gulf RACE), a prospective multi-national, multicenter registry of patients hospitalized with ACS in six Middle East countries. The present analysis was focused on participants admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 and were analyzed in terms of HF (Killip class II/III and IV) on admission. Of 1691 patients (mean age: 52.6 ± 11.7 years; 210 Females, 1481 Males) with ACS, 356 (21%) had an admission diagnosis of HF (Killip class II/III and IV). HF patients were less frequently males (19.2% vs. 34.3%; P < 0.001). HF was more frequently associated with hypertension (64.3% vs. 43.9%; P < 0.001), hyperlipidemia (49.4% vs. 31.8%; P < 0.001) and diabetes mellitus (DM) (51.1% vs. 36.2%; P < 0.001). HF was significantly associated with in-hospital mortality (OR = 11.821; 95% CI: 5.385-25.948; P < 0.001). In multivariate logistic regression, age, hyperlipidemia, heart rate and DM were associated with higher in-hospital HF.
HF is observed in about 1 in 5 patients with ACS in the UAE and is associated with a significant increase in in-hospital mortality and other adverse outcomes.
PMCID: PMC3527184  PMID: 23014157
Heart failure; Acute coronary syndrome; United Arab Emirates
4.  Characteristics, Management, and In-Hospital Outcomes of Diabetic Patients with Acute Coronary Syndrome in the United Arab Emirates 
The Scientific World Journal  2012;2012:698597.
We describe the baseline characteristics, management, and in-hospital outcomes of patients in the United Arab Emirates (UAE) with DM admitted with an acute coronary syndrome (ACS) and assess the influence of DM on in-hospital mortality. Data was analyzed from 1697 patients admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 as part of the 1st Gulf RACE (Registry of Acute Coronary Events). Of 1697 patients enrolled, 668 (39.4%) were diabetics. Compared to patients without DM, diabetic patients were more likely to have a past history of coronary artery disease (49.1% versus 30.1%, P < 0.001), hypertension (67.2% versus 36%, P < 0.001), and prior revascularization (21% versus 11.4%, P < 0.001). They experienced more in-hospital recurrent ischemia (8.5% versus 5.1%; P = 0.004) and heart failure (20% versus 10%; P < 0.001). The mortality rate was 2.7% for diabetics and 1.6% for nondiabetics (P = 0.105). After age adjustment, in-hospital mortality increased by 3.5% per year of age (P = 0.016). This mortality was significantly higher in females than in males (P = 0.04). ACS patients with DM have different clinical characteristics and appear to have poorer outcomes.
PMCID: PMC3385598  PMID: 22778703
5.  Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events 
Background and aims
Metabolic syndrome (MetS) is associated with increased prevalence of echocardiographic LV hypertrophy (LVH), a potent predictor of cardiovascular (CV) outcome. Whether MetS increases risk of CV events independently of presence of LVH has never been investigated. It is also unclear whether LVH predicts CV risk both in the presence and absence of MetS.
Methods and Results
Participants in the 2nd Strong Heart Study examination without prevalent coronary heart disease, congestive heart failure or renal insufficiency (plasma creatinine>2.5 mg/dL) were studied (n=2,758; 1,746 women). MetS was defined by WHO criteria. Echocardiographic LV hypertrophy was defined using population-specific cut-point value for LV mass index (>47.3 g/m2.7). After controlling for age, sex, LDL-cholesterol, smoking, plasma creatinine, diabetes, hypertension and obesity, participants with MetS had greater probability of LVH than those without MetS (OR=1.55 [1.18-2.04], p<0.002). Adjusted hazard of composite fatal and non-fatal CV events was greater when LVH was present, in participants without (HR=2.03 [1.33-3.08]) or with MetS (HR=1.64 [1.31-2.04], both p<0.0001), with similar adjusted population attributable risk (12% and 14%). After adjustment for LVH, risk of incident CV events remained 1.47-fold greater in MetS (p<0.003), an effect, however, that was not confirmed when diabetic participants were excluded.
LVH is a strong predictor of composite 8-year fatal and non-fatal CV events either in the presence or in the absence of MetS and accounts for a substantial portion of the high CV risk associated with MetS.
PMCID: PMC2729242  PMID: 18674890
6.  Identifying primary care patients at risk for future diabetes and cardiovascular disease using electronic health records 
Prevention of diabetes and coronary heart disease (CHD) is possible but identification of at-risk patients for targeting interventions is a challenge in primary care.
We analyzed electronic health record (EHR) data for 122,715 patients from 12 primary care practices. We defined patients with risk factor clustering using metabolic syndrome (MetS) characteristics defined by NCEP-ATPIII criteria; if missing, we used surrogate characteristics, and validated this approach by directly measuring risk factors in a subset of 154 patients. For subjects with at least 3 of 5 MetS criteria measured at baseline (2003-2004), we defined 3 categories: No MetS (0 criteria); At-risk-for MetS (1-2 criteria); and MetS (≥ 3 criteria). We examined new diabetes and CHD incidence, and resource utilization over the subsequent 3-year period (2005-2007) using age-sex-adjusted regression models to compare outcomes by MetS category.
After excluding patients with diabetes/CHD at baseline, 78,293 patients were eligible for analysis. EHR-defined MetS had 73% sensitivity and 91% specificity for directly measured MetS. Diabetes incidence was 1.4% in No MetS; 4.0% in At-risk-for MetS; and 11.0% in MetS (p < 0.0001 for trend; adjusted OR MetS vs No MetS = 6.86 [6.06-7.76]); CHD incidence was 3.2%, 5.3%, and 6.4% respectively (p < 0.0001 for trend; adjusted OR = 1.42 [1.25-1.62]). Costs and resource utilization increased across categories (p < 0.0001 for trends). Results were similar analyzing individuals with all five criteria not missing, or defining MetS as ≥ 2 criteria present.
Risk factor clustering in EHR data identifies primary care patients at increased risk for new diabetes, CHD and higher resource utilization.
PMCID: PMC2753330  PMID: 19772639
7.  The Relationship Between Metabolic Syndrome and Target Organ Damage in Ghanaian With Stage-2 Hypertension 
Ghana Medical Journal  2013;47(4):189-196.
To determine the frequency of Metabolic syndrome (MetS) in stage-2 hypertension and to assess the influence of MetS components over target organ damage (TOD) in Ghanaian patients.
Forty adult patients with stage-2 hypertension were enrolled in a cross-sectional study developed at the Police Hospital, Accra, between 1st February 2009 and 31st January 2010. Diagnosis of MetS was based on The National Cholesterol Education Program in Adult Treatment Panel Revised in 2005 criteria. The alterations on the heart, aortic and carotid arteries, retina, and kidneys were evaluated through the clinical examination including retinal funduscopy, chest X-Ray, ECG, and serum creatinine quantification. The Brain CT-scan was performed on the patients with clinical cerebrovascular disease manifestations.
MetS was diagnosed in 25 cases (62.5%); female sex revealed significant association with MetS (OR, 4.88; 95% CI, 1.19–19.94; P=0.027). Ninety-five percent of patients had TOD. Coronary disease was associated with MetS (OR, 4.43; 95% CI, 1.026–19,27; P=0.047) and diabetes mellitus as single MetS component (OR, 14.00; 95% CI, 1.56–125.61; P=0.018). A positive significant correlation was shown of age with cerebrovascular disease (r=0.381; P=0.015) and coronary disease (r=0.623; P=0.000). Non-significant correlation or association (P>0.05) was shown between number of MetS components and number of TOD.
In stage-2 hypertension patients a high frequency of MetS with a risk increase in female sex was observed. This stage hypertension is for itself an individual risk to develop cardiovascular disease with high frequency none related with MetS, although coronary disease risk was increased in diabetic patients.
PMCID: PMC3961852  PMID: 24669025
Cardiovascular Disease; Ghana; Hypertension; Metabolic Syndrome; X Syndrome
8.  Metabolic Syndrome, Inflammation, and the Incident Heart Failure in the Elderly: the Cardiovascular Health Study 
Circulation. Heart failure  2008;1(4):242-248.
Inflammation markers and MetS are associated with risk of CHF. We evaluated whether combining inflammation markers and metabolic syndrome (MetS) provided additive information for incident congestive heart failure (CHF), and if incorporating inflammation markers to the MetS definition added prognostic information.
Methods and Results
We studied 4017 men and women ≥ 65 years old, without baseline CHF or diabetes, participating in the Cardiovascular Health Study, an observational study with 12.2 years follow-up and 966 cases of incident CHF. Baseline “C-reactive protein (CRP)-MetS” or “interleukin-6 (IL-6)-MetS” were defined as presence of 3 out of 6 components, with elevated CRP (≥3 mg/L) or IL-6 (≥2.21 pg/mL) as a 6th component added to ATPIII criteria. Cox models adjusted for CHF risk factors and incident coronary disease, were used to calculate HRs for CHF. MetS and elevated inflammation markers were independently associated with CHF risk (HRs, 95 % CI: 1.32, 1.16–1.51 for MetS; 1.53, 1.34–1.75 for CRP; 1.37, 1.19–1.55 for IL-6). There was a 20% relative excess risk attributed to the combination of MetS and CRP (95% CI −44% to 88%). CRP-MetS and IL-6-MetS definitions reclassified 18% and 13%, respectively of participants as MetS. Both CRP-MetS and IL-6-MetS increased risk of CHF by 60% compared to those without MetS.
MetS and inflammation markers provided additive information on CHF risk in this elderly cohort. Inflammation-incorporated MetS definitions identified more participants with the same risk level as ATPIII MetS. Considering inflammation markers and MetS together may be useful in clinical and research settings.
PMCID: PMC2762642  PMID: 19808298
heart failure; metabolism; inflammation
9.  Prevalence of the metabolic syndrome and its components in Northwest Russia: the Arkhangelsk study 
BMC Public Health  2010;10:23.
The metabolic syndrome (MetS) is a cluster of risk factors associated with morbidity from cardiovascular disease (CVD) and associated mortality. Russia has one of the highest CVD mortality rates in the world. However, the prevalence of MetS in Russia remains largely unknown. The aim of this study is to estimate the prevalence of MetS and its components in an urban Russian setting.
Altogether, 3705 Russian adults aged 18-90 years were enrolled in a cross-sectional study in Arkhangelsk (Northwest Russia). All subjects completed a questionnaire and underwent a physical examination. Blood samples were taken and analyzed in TromsØ, Norway. Three separate modified definitions of MetS were used, namely, the National Education Cholesterol Education Program Adult Treatment Panel III (NCEP), the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF). To ensure comparability of the findings, the prevalence data were standardized using world and European standard populations and Russian population.
The age-standardized (Segi's world standard population) prevalence rates of the MetS among women were 19.8% (95% CI: 18.1-21.5), 20.6% (95% CI: 18.9-22.3) and 23.1% (95% CI: 21.3-24.9) by the NCEP, AHA/NHLBI and IDF criteria, respectively. The corresponding rates for men were 11.5% (95% CI: 10.1-12.9), 13.7% (95% CI: 12.2-15.2) and 11.0% (95% CI: 9.7-12.4). Among subjects with MetS, central obesity was more common among women, while elevated triglycerides and blood glucose were more common among men. Almost perfect agreement was found between the NCEP and AHA/NHLBI criteria (κ = 0.94). There was less agreement between the used definitions of MetS in men than in women.
While the prevalence of MetS among Russian women is comparable to the data for Europe and the U.S., the prevalence among Russian men is considerably lower than among their European and North-American counterparts. Our results suggest that MetS is unlikely to be a major contributor to the high cardiovascular mortality among Russian men. Further studies of MetS determinants and associated cardiovascular risk are needed for a better understanding of the mechanisms leading to the exceptionally high cardiovascular mortality in Russia.
PMCID: PMC2832773  PMID: 20085638
10.  The association and predictive value analysis of metabolic syndrome on diastolic heart failure in patients at high risk for coronary artery disease 
The purpose of the present study was to evaluate the effect and predictive value of metabolic syndrome (MetS) and its components on diastolic heart failure (DHF) in patients at high risk for coronary artery disease (CAD).
Materials and methods
We enrolled 261 patients with normal left ventricular ejection fraction (≥50%) who were scheduled to undergo coronary angiography for suspected myocardial ischemia. They were categorized into three groups (non-MetS, pre-MetS and MetS) based on the number of MetS criteria. Echocardiography was used to assess left ventricular (LV) diastolic function. The association between MetS and DHF was assessed by multivariate logistic regression (MLR) analysis (non-DHF patients as reference group) after controlling for confounders. The predictive performance of the MetS severity score (MSS) was evaluated using the area under the receiver-operating characteristic curve (AUC).
A tendency toward increased DHF prevalence with increasing MSS was found (p < 0.001). MLR analysis showed that in patients with an MSS of 1, the odds ratio (OR) of DHF was 1.60 (95% confidence interval-CI, 1.19–2.16; p = 0.02) compared to non-DHF patients; in patients with MSS ≥4, the OR was 6.61 (95% CI, 4.90–8.90; p < 0.001) compared to non-DHF patients. MSSs strongly predicted DHF (AUC = 0.73, 95% CI, 0.66–0.78, p < 0.001). MLR with MetS components as binary variables showed that blood pressure (BP) and triglycerides (TGs) were significantly associated with DHF (P = 0.001 and 0.043, respectively).
Our findings signify that MetS and its components of BP or TG were associated with DHF in high-risk CAD patients. DHF prevalence tends to increase with increasing MSS that has a high value in predicting DHF in high-risk CAD patients.
PMCID: PMC3698118  PMID: 23800086
Metabolic syndrome; Diastolic heart failure; High-risk patients; Association; Coronary artery disease
11.  Metabolic Syndrome among Emirati Adolescents: A School-Based Study 
PLoS ONE  2013;8(2):e56159.
Population-based data on metabolic syndrome (MetS) among children is lacking in the United Arab Emirates which has among the highest rates of diabetes in the world. In this study we determined the prevalence of MetS and its correlates in a sample of adolescents.
Materials and Methods
A cross-sectional school-based study was conducted on 1,018 adolescents (48.4% girls) aged 12–18 years from Al Ain Abu Dhabi Emirates. A self-administered questionnaire was used to assess socio-demographic characteristics, physical activity and dietary habits. Blood pressure, height, weight, waist circumference, fasting glucose, HDL-cholesterol and triglycerides were measured. MetS was defined using the International Diabetes Federation (IDF) criteria.
The prevalence of metabolic syndrome was 13%. Boys compared to girls were more likely to have MetS (21% vs. 4%, odds ratio [OR]: 6.57, 95%CI: 4.01 to 10.75). The prevalence of MetS increased with increase in body mass index and reached 59 percent in obese boys. After multivariable adjustment boys who were overweight (adjusted OR: 2.72 [1.37 to 5.35]), or obese (AOR: 12.70 [7.31 to 22.05]), or spent two or more than two hours on screen in a day (AOR: 1.65 [1.01 to 2.69) were more likely to have MetS. Girls who were overweight (AOR: 4.23 [1.32 to 13.62]) or obese (AOR: 8.32 [2.73 to 25.32]) were more likely to have MetS.
The prevalence of MetS is high among UAE boys. Population-based strategies are needed to address the high burden of metabolic syndrome targeted at the identified risk factors.
PMCID: PMC3572014  PMID: 23418529
12.  Cross-Sectional Assessment of Nut Consumption and Obesity, Metabolic Syndrome and Other Cardiometabolic Risk Factors: The PREDIMED Study 
PLoS ONE  2013;8(2):e57367.
Prospective studies have consistently suggested that nut consumption is inversely related to fatal and non-fatal coronary heart disease. Limited data are available on the epidemiological associations between nut intake and cardiometabolic risk factors.
To evaluate associations between frequency of nut consumption and prevalence of cardiometabolic risk factors [obesity, metabolic syndrome (MetS), type-2 diabetes, hypertension, and dyslipidemia] in a Mediterranean population at high cardiovascular risk.
Materials and Methods
Cross-sectional study of 7,210 men and women (mean age, 67 y) recruited into the PREDIMED study. MetS was defined by the harmonized ATPIII and IDF criteria. Diabetes and hypertension were assessed by clinical diagnosis and dyslipidemia (high triglycerides, low HDL-cholesterol, and hypercholesterolemia) by lipid analyses. Nut consumption was assessed using a validated food frequency questionnaire and categorized as <1, 1–3, and >3 servings/wk. Control of confounding was done with multivariate logistic regression.
Compared to participants consuming <1 serving/wk of nuts, those consuming >3 servings/wk had lower adjusted odds ratios (OR) for obesity (0.61, 95% confidence interval 0.54 to 0.68; P-trend <0.001), MetS (0.74, 0.65 to 0.85; P-trend<0.001), and diabetes (0.87, 0.78 to 0.99; P-trend = 0.043). Higher nut consumption was also associated with lower risk of the abdominal obesity MetS criterion (OR 0.68, 0.60 to 0.79; P-trend<0.001). No significant associations were observed for the MetS components high blood pressure, dyslipidemia, or elevated fasting glucose.
Nut consumption was inversely associated with the prevalence of general obesity, central obesity, MetS, and diabetes in subjects at high cardiovascular risk.
PMCID: PMC3583833  PMID: 23460844
13.  Postprandial lipemia in men with metabolic syndrome, hypertensives and healthy subjects 
The metabolic syndrome (MetS), as well as postprandial hypertriglyceridemia, is associated with coronary heart disease. This study aimed to evaluate the postprandial lipemia after oral fat tolerance test (OFTT) in subjects with MetS and compare them to hypertensive (HTN) and healthy subjects.
OFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG ≥ 150 [MetS+TG, (n = 22)] or <150 mg/dl [MetS-TG (n = 11)], and into those with or without hypertension [MetS+HTN (n = 24), MetS-HTN (n = 9), respectively]. TG concentrations were measured before and at 4, 6 and 8 h after OFTT and the postprandial response was quantified using the area under the curve (AUC) for TG.
The postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 ± 1016 vs. 1620 ± 494 and 1019 ± 280, respectively, p ≤ 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001).
Fasting TG concentration is the main determinant of postprandial lipemia. However, an exaggeration of TG postprandialy was found in normotriglyceridemic MetS and HTN compared to healthy subjects. This suggests that intervention to lower fasting TG levels should be recommended in MetS subjects.
PMCID: PMC1274342  PMID: 16197542
14.  Reduced circulating sTWEAK levels are associated with metabolic syndrome in elderly individuals at high cardiovascular risk 
The circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) is a cytokine that modulates inflammatory and atherogenic reactions related to cardiometabolic risk. We investigated the association between sTWEAK levels and metabolic syndrome (MetS) and its components in older subjects at high cardiovascular risk.
Cross-sectional analysis of 452 non-diabetic individuals (men and women aged 55–80 years) at high cardiovascular risk. MetS was defined by AHA/NHLBI and IDF criteria. Logistic regression analyses were used to estimate odds ratios (ORs) for MetS and its components by tertiles of serum sTWEAK concentrations measured by ELISA.
sTWEAK concentrations were lower in subjects with MetS than in those without. In gender- and age-adjusted analyses, subjects in the lowest sTWEAK tertile had higher ORs for overall MetS [1.71 (95% CI, 1.07-2.72)] and its components abdominal obesity [2.01 (1.15-3.52)], hyperglycemia [1.94 (1.20-3.11)], and hypertriglyceridemia [1.73 (1.05-2.82)] than those in the upper tertile. These associations persisted after controlling for family history of diabetes and premature coronary heart disease, lifestyle, kidney function and other MetS components. sTWEAK concentrations decreased as the number of MetS components increased. Individuals in the lowest vs the upper sTWEAK tertile had an increased risk of disclosing greater number of MetS features. Adjusted ORs for individuals with 2 vs ≤1, 3 vs ≤1, and ≥4 vs ≤ 1 MetS components were 2.60 (1.09-6.22), 2.83 (1.16-6.87) and 6.39 (2.42-16.85), respectively.
In older subjects at high cardiovascular risk, reduced sTWEAK levels are associated with MetS: abdominal obesity, hypertriglyceridemia and hyperglycemia are the main contributors to this association.
PMCID: PMC3974038  PMID: 24565471
sTWEAK; Metabolic syndrome; Cardiovascular risk; Biomarkers; Insulin resistance
15.  Insulin resistance is significantly associated with the metabolic syndrome, but not with sonographically proven peripheral arterial disease 
Insulin resistance (IR) is the key feature of the metabolic syndrome (MetS); its association with peripheral arterial disease (PAD) is unclear. We hypothesized that IR is associated with both the MetS and sonographically proven PAD.
IR was determined by the Homeostasis Model Assessment (HOMA) index in 214 patients with sonographically proven PAD as well as in 197 controls, who did not have a history of PAD and in whom coronary artery disease was ruled out angiographically; the MetS was defined according to NCEP-ATPIII criteria.
HOMA IR scores were significantly higher in MetS patients than in subjects without the MetS (5.9 ± 6.2 vs. 2.9 ± 3.9; p <0.001). However, HOMA IR did not differ significantly between patients with PAD and controls (4.2 ± 5.4 vs. 3.3 ± 4.3; p = 0.124). When both, the presence of MetS and of PAD were considered, HOMA IR was significantly higher in patients with the MetS both among those with PAD (6.1 ± 5.7 vs. 3.6 ± 5.2; p<0.001) and among controls (5.8 ± 6.8 vs. 2.3 ± 1.8; p <0.001), whereas it did not differ significantly between patients with PAD and controls among patients with the MetS (5.8 ± 6.8 vs. 6.1 ± 5.7; p = 0.587) nor among those without the MetS (2.3 ± 1.8 vs. 3.6 ± 5.2; p = 0.165). Similar results were obtained with the International Diabetes Federation definition of the MetS.
IR is significantly associated with the MetS but not with sonographically proven PAD.
PMCID: PMC3720189  PMID: 23866050
HOMA index; Atherothrombosis; Atherosclerosis; Insulin; Metabolic disorder
16.  Metabolic syndrome is not associated with reduction in aortic distensibility in subjects with type 2 diabetes mellitus 
Aortic distensibility (AD) is a marker of the elastic properties of the aorta. Reduction of AD occurs early in subjects with type 2 diabetes mellitus (T2DM) and it is associated with subclinical generalized atherosclerosis. Metabolic syndrome (MetS) is common in subjects with T2DM and predicts cardiovascular morbidity and mortality. This study examined the potential relationship between MetS and AD in a cohort of subjects with T2DM.
Methods and results
A total of 210 subjects with T2DM were studied. MetS was diagnosed using the NCEP/ATP-III criteria. AD was assessed non-invasively by ultrasonography. The prevalence of MetS was 64.8%. AD was not significantly different between subjects with and without MetS (1.80 ± 0.54 vs. 1.84 ± 0.53 10-6 dyn-1 cm2, p = 0.55). Univariate linear regression analysis showed that AD was associated positively with male sex (p = 0.02) as well as glomerular filtration rate (p < 0.001), and negatively with age (p = 0.04), history of hypertension (p = 0.001), as well as duration of diabetes (p < 0.001). After multivariate adjustment, AD was associated independently and significantly only with age (p = 0.02), duration of diabetes p < 0.001), and history of hypertension (p = 0.004); no significant relationship was found with MetS status, the sum of the components of the MetS or the individual components-besides hypertension-of the MetS.
In subjects with T2DM, MetS status per se is not associated with reduction of AD. In addition, it was shown that besides ageing, duration of glycemia was a strong predictor of AD. From the components of the MetS only hypertension was associated with reduction of the elastic properties of the aorta.
PMCID: PMC2235836  PMID: 18171473
17.  The Effect of Bariatric Surgery on the Metabolic Syndrome: A Population-based, Long-term Controlled Study 
To assess the effect of weight loss by bariatric surgery on metabolic syndrome (MetS) prevalence and to examine predictors of MetS resolution.
Patients and Methods
We performed a population-based, retrospective study between January 1st,1990 and December 31st,2003 of patients evaluated for bariatric surgery with AHA/NHLBI-defined MetS (increased triglycerides, low high density lipoprotein, increased blood pressure, increased fasting glucose, and a measure of obesity). There were 180 Roux-en-Y gastric bypass patients and 157 non-operative patients assessed in a weight-reduction program. We determined the change in MetS prevalence and used logistic regression models to determine predictors of MetS resolution.
Mean follow-up was 3.4 years. All MetS components improved in the surgical group and medication use decreased. Non-operative patients had improvements in high density lipoprotein. Of the 180 surgical patients, MetS prevalence decreased from 156 patients (87%) to 53 (29%), and from 133 patients (85%) to 117 (75%) in the non-operative group. There was a relative risk reduction of 0.59 (95% CI 0.48-0.67; p<0.001)] with bariatric surgery patients having MetS at follow-up. The number needed to treat with surgery to resolve one case of MetS was 2.1. Results were similar after excluding patients with diabetes or cardiovascular disease or after using non-BMI diagnostic criteria for MetS. Significant predictors of MetS resolution included a 5% loss in excess weight (OR 1.26; 95%CI 1.19-1.34;p<0.001) and diabetes (OR 0.32; 95%CI 0.15-0.68;p=0.003).
Roux-en-Y gastric bypass induces considerable and persistent improvement in MetS prevalence. Our results suggest that reversibility of MetS depends more on the amount of excess weight lost than on other parameters.
PMCID: PMC2714704  PMID: 18674474
Bariatric Surgery; Metabolic Syndrome; Weight Loss; Obesity
18.  A Twin Study of Metabolic Syndrome and Autonomic Tone 
One possible mechanism of higher cardiovascular mortality associated with the metabolic syndrome (MetS) may be through abnormal modulation in autonomic tone.
Methods and Results
We examined the association between the MetS and autonomic tone as measured by heart rate variability (HRV) among 288 twins from the Twins Heart Study. Of the 288 participants, 151 (52%) had the MetS. The MetS was associated with decreased HRV across all frequency ranges, and each additional MetS risk factor was associated with lower HRV. After adjustment for several potential confounders, very-low frequency (p<0.001), low frequency (p<0.001), and total power (p=.02) spectra of HRV remained significantly lower in twins with a progressively higher number of MetS components (18-50% decrease comparing twins with 5 risk factors to those with no risk factors). Among 87 twin pairs who were discordant for the number of MetS components, a one-unit increment in MetS components was associated with an 8% smaller very-low frequency (p=0.03) and a 15% smaller low frequency spectrum (p=0.002) comparing each twin with his brother.
MetS was associated with lower HRV in a well-characterized sample of middle-aged male twins. This association persisted even after controlling for genetic and shared environmental factors accounted for by comparison within twin pairs. Abnormalities of autonomic tone, as evidenced by lower HRV, may be partly responsible for the higher rate of atrial fibrillation, coronary heart disease, cardiac death, and overall mortality seen in patients with the MetS.
PMCID: PMC2722434  PMID: 19054251
metabolic syndrome; heart rate variability; autonomic nervous system; twins
19.  Impact of Metabolic Syndrome on the Prognosis of Ischemic Stroke Secondary to Symptomatic Intracranial Atherosclerosis in Chinese Patients 
PLoS ONE  2012;7(12):e51421.
To analyze the effect of metabolic syndrome (MetS) on prognosis of ischemic stroke secondary to intracranial stenosis in Chinese patients.
A prospective cohort of 701 patients with ischemic stroke, caused by intracranial stenosis, were followed at 3-month intervals for 1 year to monitor development of recurrent stroke or death. Imaging was performed using magnetic resonance angiography. MetS was defined using International Diabetes Federation (IDF) criteria.
MetS was identified in 26.0% of the cohort of stroke patients. Patients with MetS were more likely to be female, nonsmokers, and more likely to have a prior history of diabetes mellitus, high blood glucose and a family history of stroke than patients without MetS. During 1-year follow-up, patients with MetS had a non-significantly higher rate of stroke recurrence (7.1%) than patients without MetS (3.9%; P = 0.07). There was no difference in mortality (3.3% versus 3.5%, respectively). Multivariate Cox proportional hazards analysis (adjusting for gender, BMI, smoking, diabetes, and LDL-C) identified an association between that 1-year stroke recurrence and the presence of MetS (hazard ratio 2.30; 95% CI: 1.01–5.22) and large waist circumference (hazard ratio: 2.39; 95% CI: 1.05–5.42). However, multivariable analysis adjusting for the individual components of MetS found no significant associations between MetS and stroke recurrence. There were no associations between these parameters and mortality.
Chinese patients with symptomatic intracranial atherosclerosis who have MetS, are at higher risk of recurrent stroke than those without MetS. However, MetS was not predictive of stroke recurrence beyond its individual components and one-year mortality.
PMCID: PMC3519650  PMID: 23251528
20.  Metabolic syndrome and gallstone disease 
AIM: To investigate the association between metabolic syndrome (MetS) and the development of gallstone disease (GSD).
METHODS: A cross-sectional study was conducted in 7570 subjects (4978 men aged 45.0 ± 8.8 years, and 2592 women aged 45.3 ± 9.5 years) enrolled from the physical check-up center of the hospital. The subjects included 918 patients with gallstones (653 men and 265 women) and 6652 healthy controls (4325 men and 2327 women) without gallstones. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG) and serum lipids and lipoproteins levels were measured. Colorimetric method was used to measure cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dextrose oxidizing enzyme method was used to measure FPG. Subjects were asked to complete a questionnaire that enquired about the information on demographic data, age, gender, histories of diabetes mellitus, hypertension, and chronic liver disease and so on. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III (ATP III) criteria. Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or attenuated ultrasound transmission.
RESULTS: Among the 7570 subjects, the prevalence of the gallstone disease was 12.1% (13.1% in men and 10.2% in women). BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose and serum triglyceride (TG) in cases group were higher than in controls, while serum high-density lipid was lower than in controls. There were significant differences in the waist circumference, blood pressure, FPG and TG between cases and controls. In an age-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease. The age-adjusted odds ratio of MetS for GSD in men was 1.29 [95% confidence interval (CI), 1.09-1.52; P = 0.0030], and 1.68 (95% CI, 1.26-2.25; P = 0.0004) in women; the overall age-adjusted odds ratio of MetS for GSD was 1.42 (95% CI, 1.23-1.64; P < 0.0001). The men with more metabolic disorders had a higher prevalence of gallstone disease, the trend had statistical significance (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 3.4 times (P < 0.0001). The prevalence of GSD in women who had 5 components of MetS was 5 times higher than in those without MetS component. The more the components of MetS, the higher the prevalence of GSD (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 4.0 times.
CONCLUSION: GSD appears to be strongly associated with MetS, and the more the components of MetS, the higher the prevalence of GSD.
PMCID: PMC3422804  PMID: 22919256
Gallstone disease; Obesity; Hypertension; Dyslipidemia; Metabolic syndrome
21.  The Influence of Metabolic Syndrome on Hemodialysis Access Patency 
Journal of vascular surgery  2012;56(6):1656-1662.
The natural history of patients with Metabolic Syndrome (MetS) undergoing hemodialysis access placement is unknown. MetS has previously been found as a risk factor for poor outcomes for vascular surgery patients undergoing other interventions. The aim of this is study is to describe the outcomes of MetS patients undergoing primary hemodialysis access placement.
The medical records of all patients undergoing arteriovenous fistula placement between 1999 and 2009 at the VA Connecticut Healthcare system were reviewed (n=187). Survival, primary patency, and secondary patency were evaluated using the Gehan-Breslow test for survival. MetS was defined as the presence of three or more of the following: blood pressure ≥130 mmHg/≥90 mmHg; triglycerides ≥150 mg/dl; high-density lipoproteins (HDL) ≤50 mg/dl for women and ≤40 mg/dl for men; Body Mass Index (BMI) ≥30 kg/m2; fasting blood glucose ≥110 mg/dl.
One hundred and eighty-seven patients underwent hemodialysis access placement. One hundred and fifteen (61%) of the patients were identified to have MetS. The distribution of MetS factors among all patients were: 98% were hypertensive.; 58% patients were diabetic; 39% patients had elevated triglycerides; 60% of patients had decreased HDL; 36% of patients had an elevated BMI. 39% of patients were currently receiving hemodialysis. The mean age of patients was 66 years. The median length of follow-up was 4.2 years. The forearm was site of fistula placement in 53% of patients; no difference existed between groups (57% for MetS, 50% for No MetS, p = 0.388). The median time to primary failure was 0.46 years for all patients (0.555 years[No MetS], 0.436 years [MetS]; p = 0.255). Secondary patency was 50% at 1.18 years for all patients (1.94 years [No MetS], 0.72 years [MetS]; p = 0.024). Median survival duration for all patients was 4.15 years (5.07 years [No MetS], 3.63 years [MetS]; p = 0.019).
MetS is prevalent among patients undergoing hemodialysis access placement. Patients with MetS have equivalent primary patency rates, however their survival and cumulative patency rates are significantly lower compared to those patients without MetS. Patients with MetS form a high-risk group of patients that need intensive surveillance protocols.
PMCID: PMC3508093  PMID: 22959367
Hemodialysis access; renal insufficiency; metabolic syndrome
22.  Association of epicardial fat with left ventricular diastolic function in subjects with metabolic syndrome: assessment using 2-dimensional echocardiography 
Metabolic syndrome (MetS) is related with left ventricular diastolic dysfunction (LVDD) and poor cardiovascular outcome. Epicardial adipose tissue (EAT) thickness, measured by echocardiography, is increased in subjects with MetS. However, the association of EAT with LV diastolic function has not been evaluated in subjects with MetS.
In this retrospective study, EAT thickness was measured in 1,486 consecutive asymptomatic patients with no known heart disease who had transthoracic echocardiography during a self-referred healthcare exam. Subjects with a history of ischemic heart disease, cardiomyopathy or significant valvular heart disease were excluded. LVDD was defined as E/e’ ratio ≥ 15. Subjects were grouped into two groups, those with MetS and those without.
MetS was present in 346 subjects. There was no difference in LV systolic function between the two groups. However compared to patients without MetS, patients with MetS had larger left atrium (LA) size and higher E/e’ ratio (38 ± 5 versus 35 ± 5 mm for LA and 10.0 ± 3.3 versus 8.7 ± 2.7 for E/e’ ratio in subjects with versus without MetS both p < 0.001). LVDD was found in 27 (7.8%) subjects with MetS, compared to 30 (2.6%) subjects without MetS (p < 0.001). In subjects with MetS, EAT was significantly correlated with LVDD, even after adjusting for other cardiometabolic risk factors such as age, systolic blood pressure, BMI, blood glucose and LDL cholesterol (OR 1.845, 95% CI 1.153-2.951, p = 0.011).
Greater EAT is found in subjects with MetS. EAT is significantly associated with LVDD in subjects with MetS, even after adjusting for other risk factors.
PMCID: PMC3890512  PMID: 24406059
Epicardial fat; Diastolic function; Metabolic syndrome
23.  Prevalence of Metabolic Syndrome Is Higher among Non-Obese PCOS Women with Hyperandrogenism and Menstrual Irregularity in Korea 
PLoS ONE  2014;9(6):e99252.
Hyperandrogenism (HA) has been linked with several components of metabolic syndrome (MetS). Few studies in Asian women have evaluated the important risk factors for and prevalence of MetS according to PCOS subtype. In this study, we investigated differences in metabolic parameters and the prevalence of MetS in two major phenotypic subgroups of PCOS in Korea. Furthermore, we investigated the relationship between HA-associated parameters and MetS.
Materials and Methods
This cross-sectional observational study was conducted from May 2010 to December 2011 in Korea. A total of 837 females with PCOS, aged 15–40, were recruited from Departments of Obstetrics and Gynecology at 13 hospitals. Of those, 700 subjects with either polycystic ovaries (PCO)+HA+oligomenorrhea/amenorrhea (O) or PCO+O were eligible for this study. MetS was diagnosed according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines and the International Diabetes Federation (IDF) criteria.
MetS was more prevalent in the PCO+HA+O group (19.7%) than in the PCO+O (11.9%) group. There were statistically significant trends for an increased risk of MetS in the PCO+HA+O group compared to the PCO+O group. After adjustment for age, the odds ratio of MetS was 2.192 in non-obese subjects with PCO+HA+O compared to those with PCO+O, whereas the risk of MetS was not different in obese patients. Multivariate logistic regression analysis showed that high free androgen index and low sex hormone-binding globulin were significantly associated with MetS in non-obese women with PCOS, with odds ratios of 4.234 (95% CI, 1.893–9.474) and 4.612 (95% CI, 1.978–10.750), respectively. However, no associations were detected between MetS and SHBG and FAI in obese PCOS subjects.
Our results indicate that HA and its associated parameters (FAI and SHBG) are significantly associated with MetS in non-obese PCOS subjects, whereas this association was not observed in obese subjects.
PMCID: PMC4047097  PMID: 24901345
24.  Linkage of Epidemiologic Evidence With the Clinical Aspects of Metabolic Syndrome 
Korean Circulation Journal  2012;42(6):371-378.
Metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors, such as hypertension, glucose intolerance, high triglycerides, and a low high density lipoprotein-cholesterol level. MetS is known to be associated with cardiovascular diseases. In order to diagnose MetS, definitions such as National Cholesterol Education Program Adult Treatment Panel III, American Heart Association/National Heart Lung and Blood Institute, International Diabetes Federation, World Health Organization, European Group for the Study of Insulin Resistance and American College of Endocrinology are widely used. However, using different criteria may lead to confusion regarding the diagnosis and treatment of patients with MetS in the primary care setting. Our objected was to review 3 aspects concerning MetS using the Metabolic Syndrome Research Initiatives study of 123892 healthy Koreans (1994-2001) that had a maximum follow-up of 12 years. The 3 aspects were reviewed by determination of the association of MetS with the development of atherosclerotic cardiovascular disease (ASCVD) and ischemic heart disease (IHD). Based on our findings, each metabolic factor associated with MetS was not weighted equally. The hazard ratio (HR) was higher in individuals with higher glucose compared with the HR in individuals with higher body mass index. Individuals with pre-MetS (having 1 or 2 metabolic factors) had 1.5-2.3 fold higher risk of developing ASCVD and IHD in both genders. In the presence of MetS, both singly and in combination, precede the development of ASCVD and IHD and individuals with pre-MetS must not be ignored as there is no apparent threshold in defining MetS. Furthermore, MetS may complement the Framingham Risk Score and can be used as the first line approach to treat the ASCVD or IHD.
PMCID: PMC3390421  PMID: 22787466
Metabolic cardiovascular syndrome; Atherosclerosis; Ischemic heart disease
25.  One-Year Clinical Outcomes among Patients with Metabolic Syndrome and Acute Myocardial Infarction 
Korean Circulation Journal  2013;43(8):519-526.
Background and Objectives
Metabolic syndrome (MetS) is an important risk factor for cardiovascular disease. However, the clinical outcome of acute myocardial infarction (AMI) with MetS has not been well examined. The purpose of this study was to evaluate the clinical outcomes of AMI patients with MetS.
Subjects and Methods
We evaluated a total of 6352 AMI patients who had successful percutaneous coronary interventions and could be identified for MetS between 2005 and 2008 at 51 hospitals participating in the Korea Acute Myocardial Infarction Registry. They were divided into 2 groups according to the presence of MetS: the MetS group (n=2493, 39.2%) versus the Non-MetS group (n=3859, 60.8%). In addition, 4049 AMI patients with high levels of low density lipoprotein-cholesterol (LDL-C) (≥100 mg/dL) among them, were divided into the MetS group (n=1561, 38.6%) versus the Non-MetS group (n=2488, 61.4%).
In the overall population, there was no significant difference in 12-month the major adverse cardiac events (MACE) rate between the 2 groups. However, the MetS group showed a significantly higher 12-month MACE rate in the high LDL-C population. Multivariate analysis showed that MetS was an independent prognostic factor for 12-month MACE {hazard ratio (HR) 1.607, 95% confidence interval (CI) 1.027 to 2.513, adjusted p=0.038} and for 12-month target vessel revascularization (HR 1.564, 95% CI 1.092 to 2.240, adjusted p=0.015) in the high LDL-C population.
MetS patients with AMI in the overall population showed no significant difference in 12-month clinical outcomes. However, in patients with higher LDL-C ≥100 mg/dL, they showed significantly worse clinical outcome than Non-MetS patients. Therefore, it is important to ascertain the presence of MetS in AMI patients, and more aggressive therapy should be strongly considered for AMI patient with MetS.
PMCID: PMC3772296  PMID: 24044010
Metabolic syndrome; Myocardial infarction; Low density lipoprotein-cholesterol

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