the pathogenesis of metabolic syndrome is considered as a multiple risk factor clustering , which is caused by visceral fat accumulation , in japan.1 the japanese committee for the diagnostic criteria of metabolic syndrome adopted a visceral fat area of 100 cm as the cutoff point , which was estimated by computed tomography in both men and women . furthermore , the waist circumference corresponding to a visceral fat area of 100 cm was confirmed as 85 cm in men and 90 cm in women . according to this concept , in 2005 , the japanese committee for the diagnostic criteria of metabolic syndrome defined metabolic syndrome as the presence of two or more clinical abnormalities ( three abnormalities : dyslipidemia [ serum triglyceride concentrations 150 mg / dl and/or serum high - density lipoprotein cholesterol concentrations < 40 mg / dl or under treatment ] , elevated blood pressure levels [ systolic blood pressure 130 mmhg and/or diastolic pressure 85 mmhg or under treatment ] , and elevated blood glucose levels [ fasting blood glucose 110 mg / dl or under treatment ] ) , in addition to visceral fat obesity ( waist circumference : 85 cm or more in men and 90 cm or more in women).2 metabolic syndrome is considered as not only an important cardiovascular risk factor but also a contributor to the development of type 2 diabetes in japan,35 even though the definition of metabolic syndrome in japan is different from that in other countries . clinically , the blood concentration of cardiac troponin t , a component of the troponin complex , is used as a diagnostic tool for acute myocardial infarction , because cardiac troponin t is rapidly released from the myocardium to the blood following myocardial damage.6 furthermore , recent clinical and epidemiological studies have demonstrated that the blood concentration of cardiac troponin t ( ie , high - sensitivity cardiac troponin t [ hs - ctnt ] ) , measured using a highly sensitive assay , represents a useful biomarker for evaluating the pathogenesis of heart failure or predicting cardiovascular events.79 several reports exist concerning relationships between hs - ctnt and clinical parameters such as age - related markers , in japan or other countries.8,10,11 however , little is known about the clinical significance of hs - ctnt in metabolic syndrome . in the present study , we attempted to clarify the factors important for hs - ctnt elevation in metabolic syndrome from the perspective of primary cardiovascular events . this study was conducted at the hitsumoto medical clinic in shimonoseki city , japan , between september 2011 and august 2013 . the study population comprised 258 metabolic syndrome patients who were middle - aged males diagnosed using the japanese metabolic syndrome criteria.2 subjects with a history of cardiovascular disease or those using medications such as antihyperlipidemic , antihypertensive , or antidiabetic drugs were excluded . all participants provided informed consent , and the study protocol was approved by the local ethics committee of the hitsumoto medical clinic . diagnostic parameters of metabolic syndrome in the japanese criteria and various clinical parameters , including hs - ctnt concentrations , were examined . in this study , the cardio  ankle vascular index ( cavi ) was evaluated as a marker of arterial function . cavi was measured by a standard method described previously.12 briefly , the brachial and ankle pulse waves were determined using inflatable cuffs with the pressure maintained between 30 and 50 mmhg to ensure that the cuff pressure had a minimal effect on the systemic hemodynamics . blood pressure and pulse pressure were determined simultaneously.12 these measurements were obtained with the subject in the supine position . cavi was measured after the subject had rested for 10 minutes in a quiet room . blood samples were collected from the antecubital vein in the morning after 12 hours of fasting . total cholesterol and triglyceride concentrations were measured using standard enzymatic methods . serum low - density lipoprotein cholesterol concentrations were calculated using the friedewald formula;13 subjects with serum triglyceride concentrations 400 mg / dl were excluded because of the low sensitivity of this method . glucose and insulin concentrations were measured using the glucose oxidase method and an enzyme immunoassay , respectively . to measure insulin resistance , we calculated homeostatic model assessment of insulin resistance ( homa - ir ) as follows:14 homa - ir = fasting glucose concentration ( mg / dl )  fasting insulin concentration ( g / ml)/405 . estimated glomerular filtration rate ( egfr ) was calculated using the adjusted modification of diet in renal disease study equation , which was proposed by the working group of the japanese chronic kidney disease initiative.15 the blood concentration of brain natriuretic peptide was measured using a commercial kit ( shionospot reader ; shionogi and co , ltd , osaka , japan ) . high - sensitivity c - reactive protein ( hs - crp ) concentration was measured using high - sensitivity , latex - enhanced immunonephelometry . the derivated reactive oxygen metabolites test , which reflects blood hydroperoxide concentrations , was performed using a commercial device ( diacron , grosseto , italy).16 hs - ctnt concentration was measured using a commercial kit ( roche diagnostics , rotkreuz , switzerland).17 in this assay , the lower limit of detection was 0.003 ng / ml . a commercially available statistical software program ( stat view - j 5.0 ; hulinks inc . , tokyo , japan ) was used for all statistical analyses . between - group comparisons were performed using the student s t - test or mann whitney s u - test , and the correlation coefficient was estimated using spearman s rank correlation analysis . to clarify the independent factors for hs - ctnt elevation , we performed multiple regression analysis for hs - ctnt as a subordinate factor . a p - value of < 0.05 was considered statistically significant . this study was conducted at the hitsumoto medical clinic in shimonoseki city , japan , between september 2011 and august 2013 . the study population comprised 258 metabolic syndrome patients who were middle - aged males diagnosed using the japanese metabolic syndrome criteria.2 subjects with a history of cardiovascular disease or those using medications such as antihyperlipidemic , antihypertensive , or antidiabetic drugs were excluded . all participants provided informed consent , and the study protocol was approved by the local ethics committee of the hitsumoto medical clinic . diagnostic parameters of metabolic syndrome in the japanese criteria and various clinical parameters , including hs - ctnt concentrations , were examined . in this study , the cardio  ankle vascular index ( cavi ) was evaluated as a marker of arterial function . cavi was measured by a standard method described previously.12 briefly , the brachial and ankle pulse waves were determined using inflatable cuffs with the pressure maintained between 30 and 50 mmhg to ensure that the cuff pressure had a minimal effect on the systemic hemodynamics . blood pressure and pulse pressure were determined simultaneously.12 these measurements were obtained with the subject in the supine position . cavi was measured after the subject had rested for 10 minutes in a quiet room . blood samples were collected from the antecubital vein in the morning after 12 hours of fasting . total cholesterol and triglyceride concentrations were measured using standard enzymatic methods . serum low - density lipoprotein cholesterol concentrations were calculated using the friedewald formula;13 subjects with serum triglyceride concentrations 400 mg / dl were excluded because of the low sensitivity of this method . glucose and insulin concentrations were measured using the glucose oxidase method and an enzyme immunoassay , respectively . to measure insulin resistance , we calculated homeostatic model assessment of insulin resistance ( homa - ir ) as follows:14 homa - ir = fasting glucose concentration ( mg / dl )  fasting insulin concentration ( g / ml)/405 . estimated glomerular filtration rate ( egfr ) was calculated using the adjusted modification of diet in renal disease study equation , which was proposed by the working group of the japanese chronic kidney disease initiative.15 the blood concentration of brain natriuretic peptide was measured using a commercial kit ( shionospot reader ; shionogi and co , ltd , osaka , japan ) . high - sensitivity c - reactive protein ( hs - crp ) concentration was measured using high - sensitivity , latex - enhanced immunonephelometry . the derivated reactive oxygen metabolites test , which reflects blood hydroperoxide concentrations , was performed using a commercial device ( diacron , grosseto , italy).16 hs - ctnt concentration was measured using a commercial kit ( roche diagnostics , rotkreuz , switzerland).17 in this assay , the lower limit of detection was 0.003 ng / ml . a commercially available statistical software program ( stat view - j 5.0 ; hulinks inc . , between - group comparisons were performed using the student s t - test or mann whitney s u - test , and the correlation coefficient was estimated using spearman s rank correlation analysis . to clarify the independent factors for hs - ctnt elevation , we performed multiple regression analysis for hs - ctnt as a subordinate factor . a p - value of < 0.05 was considered statistically significant . age , hs - crp concentrations , rom serum concentrations , blood concentrations of brain natriuretic peptide , and cavi were significantly higher , and egfr was significantly lower in patients with detectable hs - ctnt . however , diagnostic parameters of metabolic syndrome were not significantly different between the two groups . correlations between hs - ctnt and various clinical parameters in hs - ctnt - positive patients are shown in table 2 . age , hs - crp concentrations , rom serum concentrations , blood concentrations of brain natriuretic peptide , egfr , and cavi were significantly correlated with hs - ctnt , although diagnostic parameters of metabolic syndrome had no significant correlations with hs - ctnt . blood concentrations of brain natriuretic peptide , rom serum concentrations , cavi , and age were selected as independent variables for hs - ctnt as a subordinate factor . recently , pervanidou et al18 examined the relationship of circulating concentrations of hs - ctnt with metabolic syndrome in childhood . they reported that hs - ctnt in obese children with metabolic syndrome was higher than that in obese children without metabolic syndrome and nonobese children ; moreover , hs - ctnt did not differ between obese children without metabolic syndrome and nonobese children . these results suggest that the presence of metabolic syndrome resulted in hs - ctnt elevation at an early stage . among diagnostic parameters of metabolic syndrome , high blood glucose concentrations and high blood pressure were reported to cause myocardial damage via dysfunction of microcirculation , oxidative stress , or other pathways.1921 in clinical studies , however , relationships among blood glucose concentrations , blood pressure levels , and blood concentrations of cardiac troponin were controversial.2225 wallace et al22 reported that diabetes mellitus was independently associated with ctnt elevation in the general population . however , everett et al23 reported that no significant relationship was observed between hemoglobin a1c levels and hs - ctnt in nondiabetic subjects . mckie et al24 reported that hypertension was significantly associated with hs - ctnt in the general population . however , hoshide et al25 reported that blood pressure - lowering therapy using losartan plus hydrochlorothiazide did not lead to a significant decrease in hs - ctnt , even though blood pressure levels were decreased . insulin resistance has been considered to have an important role in the pathogenesis of metabolic syndrome . furthermore , some clinical studies reported a correlation between insulin resistance and myocardial damage.26,27 in the present study , however , homa - ir showed no significant correlation with hs - ctnt . it is well known that abnormal adipocytokine secretion is associated with the pathogenesis of metabolic syndrome . furthermore , some basic or clinical studies reported relationships between adipocytokines such as adiponectin or resistin and myocardial damage.28,29 abnormal adipocytokine secretion may be an important factor for hs - ctnt elevation in metabolic syndrome . in this study , adipocytokine concentrations were not assessed ; therefore , further studies are warranted to evaluate the relationship of adipocytokines with hs - ctnt . oxidative stress is known to be an important component in the progression of heart failure , and several pathways by which oxidative stress leads to myocardial damage have been identified , including dysfunction of the mitochondrial electron transport complex , activity of nicotinamide adenine dinucleotide phosphate oxidase , and apoptosis of myocardial cells.3032 furthermore , this study revealed the importance of oxidative stress for myocardial damage in metabolic syndrome and subclinical heart failure . among a number of markers of oxidative stress , the derivated reactive oxygen metabolites test is considered clinically useful to evaluate oxidative stress in vivo , because the measurement of rom serum concentrations is accurate and simple and it can be performed rapidly.16,33 furthermore , recent clinical studies have reported a relationship between rom and cardiovascular disease.34,35 therefore , the measurement of rom serum concentrations is expected to predict the degree of subclinical myocardial damage or primary cardiovascular events in metabolic syndrome . the stiffness index is known to reflect the stiffness of the aortic artery , and cavi is reported to reflect the stiffness index  of the thoracic aorta or the common carotid artery.36 cavi is considered as a useful physiological marker for evaluating arterial stiffness , except in patients with chronic arterial fibrillation or peripheral arterial disease , because of the low reliability of cavi . in recent years , several studies have indicated the importance of left ventricular dysfunction in the occurrence of heart failure or the progression of myocardial damage;37 furthermore , increases in aortic artery stiffness are known to cause left ventricular dysfunction . sakane et al38 reported a significant relationship between cavi and left ventricular dysfunction using ultrasonic echocardiography . therefore , the relationship between hs - ctnt and cavi identified in this study was considered to reflect myocardial damage via left ventricular dysfunction by an increase in vascular resistance or afterload . another clinical study reported that cavi reflected endothelial dysfunction.39 endothelial dysfunction has also been known to cause left ventricular dysfunction or myocardial damage;40,41 therefore , the significant correlation of hs - ctnt with cavi in metabolic syndrome patients may be partly explained by endothelial dysfunction . first , ultrasonic echocardiography , coronary angiography , or multidetector computed tomography angiography was not performed ; therefore , cardiovascular diseases such as heart failure or coronary artery disease may have remained undetected in patients . the proportion of metabolic syndrome patients in the general japanese female population is very small ( incidence : 12.1% in males , 1.7% in females).42 therefore , analysis of metabolic syndrome in females diagnosed by the japanese criteria is very difficult in the single - unit range . the relationship between hs - ctnt and metabolic syndrome in the japanese female population will be discussed in large - scale studies . third , this study was cross - sectional , and its sample size was relatively small . a large number of prospective studies , including interventional therapies , are required to clarify the clinical significance of hs - ctnt , cavi , and roms with metabolic syndrome . the study findings indicate that in vivo oxidative stress and abnormalities of arterial function are closely associated with increases in hs - ctnt concentration in japanese metabolic syndrome patients .
purposethe blood concentration of cardiac troponin t ( ie , high - sensitivity cardiac troponin t [ hs - ctnt ] ) , measured using a highly sensitive assay , represents a useful biomarker for evaluating the pathogenesis of heart failure or predicting cardiovascular events . 
 however , little is known about the clinical significance of hs - ctnt in metabolic syndrome . 
 the aim of this study was to examine the factors affecting hs - ctnt elevation in japanese metabolic syndrome patients.patients and methodswe enrolled 258 metabolic syndrome patients who were middle - aged males without a history of cardiovascular events . 
 we examined relationships between hs - ctnt and various clinical parameters , including diagnostic parameters of metabolic syndrome.resultsthere were no significant correlations between hs - ctnt and diagnostic parameters of metabolic syndrome . 
 however , hs - ctnt was significantly correlated with age ( p<0.01 ) , blood concentrations of brain natriuretic peptide ( p<0.01 ) , reactive oxygen metabolites ( markers of oxidative stress , p<0.001 ) , and the cardio  ankle vascular index ( marker of arterial function , p<0.01 ) . 
 furthermore , multiple regression analysis revealed that these factors were independent variables for hs - ctnt as a subordinate factor.conclusionthe findings of this study indicate that in vivo oxidative stress and abnormality of arterial function are closely associated with an increase in hs - ctnt concentrations in japanese metabolic syndrome patients .