current estimates suggest that more than onethird of the world population is overweight or obese . in the united states , with more than twothirds of the adult population overweight and onethird obese , obesity is closely associated with the metabolic syndrome and has been linked to adverse cardiovascular prognosis and mortality . a diagnosis of obesity predicts incident coronary artery disease ( cad ) over and above the traditional coronary risk factors and has been reported to be additive to the framingham risk score . large cohort studies as well as populationbased analysis from the oregon sudden unexpected death study ( suds ) have confirmed obesity / overweight as a risk factor for sudden cardiac death ( scd ) . the link between obesity and arrhythmia is likely multifactorial and continues to be an area of active research . obesity has been linked to left atrial and ventricular dilatation as well as left ventricular hypertrophy and diastolic dysfunction . recent animal as well as clinical studies have suggested that fatty infiltration of the myocardium may itself predispose to ventricular arrhythmia , potentially as a result of poor electrical conductivity of fat which could favor delayed impulse transmission and reentry . electrical disturbances arising as a result of fatty infiltration / fibrosis may thus represent an important mechanism of arrhythmogenesis in obesity . qrs fragmentation ( fqrs ) on the surface ecg has been reported to be a surrogate marker of inhomogeneous conduction and delayed activation in the myocardium . fragmented qrs complexes , thought to reflect myocardial scarring , have been linked to adverse cardiac prognosis as well as cardiac mortality . moreover , earlier studies have suggested that qrs fragmentation predicts risk of arrhythmia in a variety of cardiac conditions . however , a potential association between qrs fragmentation and scd in the general population needs further evaluation . it would be of significant interest to assess whether this simple , noninvasive marker on the surface ecg could help identify highrisk subgroups within the obese / overweight population . in light of the available knowledge about the pathophysiology of obesity and scd , especially with regard to the effect of obesity on cardiac structure , we postulated that qrs fragmentation may be a useful marker to identify those at risk of scd among obese / overweight subjects in the community . we therefore undertook a systematic investigation of the potential utility of qrs fragmentation , among obese / overweight subjects in the general population . briefly , cases of possible scd are prospectively ascertained in the portland , oregon metropolitan area ( population approximately 1 million ) using multiple sources , which include first responders , local hospital emergency rooms , and the county medical examiner . after detailed review of available medical records , autopsy reports , and the circumstances of arrest , scd cases are identified through a 3physician adjudication system . scd is defined as an unexpected sudden , pulseless condition of cardiac etiology , occurring within 1 hour of symptom onset in witnessed cases and within 24 hours if unwitnessed . subjects with known terminal illnesses ( such as cancer ) , noncardiac causes of sudden death ( such as cerebrovascular accident ) , and drug overdose are excluded . in parallel , controls are recruited from the same geographical location . controls are subjects with no history of cardiac arrest , and are chosen to achieve a mix of a majority of subjects with coronary artery disease ( cad ) and a minority of healthy controls from the population . the study is designed for the majority of controls ( 80% ) to have cad since published studies have established that a similar majority of scd cases in the community have associated cad . cad controls are recruited from among subjects undergoing angiography at one of the region 's major participating health systems , those who were transported by the emergency medical system ( ems ) for symptoms of acute coronary ischemia or subjects with diagnosed cad from the region 's kaiser permanente system . scd cases 50 years of age were assumed to have cad based on > 95% likelihood of cad in such cases . detailed demographic and clinical information was collected for cases and controls from available medical records . left ventricular ( lv ) function was evaluated by measurement of the lv ejection fraction ( ef ) and categorized as normal lv function ( 55% ) , mild to moderate dysfunction ( 3654% ) , or severe dysfunction ( 35% ) . body mass index ( bmi ) was calculated for subjects using weight and height measurements . as per national institute of health guidelines , overweight was defined as a bmi of 25 to 29.9 kg / m , and obesity was defined as a bmi of 30 kg / m . the present study compared obese / overweight scd cases with obese / overweight controls from the same geographical area . other than being from the same geographic location , no other specific matching was performed between cases and controls . parameters assessed from the 12lead ecg included heart rate , qrs duration , qt interval , presence of q waves , and qrs fragmentation . taking into consideration previously established criteria for assessing fqrs , the present analysis was limited to ecgs with narrow qrs ( qrs duration < 120 ms ) . the qt interval was corrected using bazett 's formula and categorized as normal or abnormal using sexspecific criteria ( men : qt c 430 ms  normal , 431 to 450 ms abnormal ; women : qtc 450 ms  normal , 451 to 470 ms  borderline , > 470 ms pathologic q waves were defined as q waves 40 milliseconds in duration and > 25% of the voltage of the following r wave . q waves were classified according to territory , based on presence in at least 2 contiguous leads , as anterior ( leads v1v5 ) , lateral ( leads i , avl , and v6 ) , and inferior ( leads ii , iii , and avf ) . fqrs was identified as previously defined by the presence of various rsr patterns with or without q wave , including an additional r wave ( r ) , notching of the r wave , notching in the nadir of the s wave , or the presence of more than 1 r ( fragmentation ) in at least 2 contiguous leads corresponding to a major coronary artery territory ( figure 1a and 1b ) . if notching was confined only to the terminal qrs accompanied by j point elevation of 0.1 mv , it was classified as early repolarization pattern rather than fragmentation . fragmentation was classified by anatomic territory , similar to q waves , into anterior ( leads v1v5 ) , lateral ( leads i , avl , and v6 ) , or inferior ( leads ii , iii , and avf ) . ecg assessment for fragmentation and q waves were performed by 2 trained readers blinded to the case / control status of the subjects . the study was approved by the institutional review boards of cedarssinai medical center , oregon health and science university , and all participating hospitals . student t tests and pearson 's  tests were used for comparisons of continuous variables ( presented as meanstandard deviation ) and categorical variables ( presented as numbers and percentages ) , respectively . multivariable logistic regression was used to estimate odds ratios ( or ) for the association of fqrs with scd case status after adjusting for parameters that were significant in the univariate analyses . for the multivariable model , qtc ( as described earlier ) and heart rate ( 100 versus < 100 bpm ) were categorized based on accepted standards . results were reported as 2tailed p values , with a p value of 0.05 being considered statistically significant . all analyses were performed using spss statistical software ( version 20.0 for windows , spss inc , ibm corporation , new york ) . briefly , cases of possible scd are prospectively ascertained in the portland , oregon metropolitan area ( population approximately 1 million ) using multiple sources , which include first responders , local hospital emergency rooms , and the county medical examiner . after detailed review of available medical records , autopsy reports , and the circumstances of arrest , scd cases are identified through a 3physician adjudication system . scd is defined as an unexpected sudden , pulseless condition of cardiac etiology , occurring within 1 hour of symptom onset in witnessed cases and within 24 hours if unwitnessed . subjects with known terminal illnesses ( such as cancer ) , noncardiac causes of sudden death ( such as cerebrovascular accident ) , and drug overdose are excluded . in parallel , controls are recruited from the same geographical location . controls are subjects with no history of cardiac arrest , and are chosen to achieve a mix of a majority of subjects with coronary artery disease ( cad ) and a minority of healthy controls from the population . the study is designed for the majority of controls ( 80% ) to have cad since published studies have established that a similar majority of scd cases in the community have associated cad . cad controls are recruited from among subjects undergoing angiography at one of the region 's major participating health systems , those who were transported by the emergency medical system ( ems ) for symptoms of acute coronary ischemia or subjects with diagnosed cad from the region 's kaiser permanente system . scd cases 50 years of age were assumed to have cad based on > 95% likelihood of cad in such cases . detailed demographic and clinical information was collected for cases and controls from available medical records . left ventricular ( lv ) function was evaluated by measurement of the lv ejection fraction ( ef ) and categorized as normal lv function ( 55% ) , mild to moderate dysfunction ( 3654% ) , or severe dysfunction ( 35% ) . body mass index ( bmi ) was calculated for subjects using weight and height measurements . as per national institute of health guidelines , overweight was defined as a bmi of 25 to 29.9 kg / m , and obesity was defined as a bmi of 30 kg / m . the present study compared obese / overweight scd cases with obese / overweight controls from the same geographical area . other than being from the same geographic location , no other specific matching was performed between cases and controls . parameters assessed from the 12lead ecg included heart rate , qrs duration , qt interval , presence of q waves , and qrs fragmentation . taking into consideration previously established criteria for assessing fqrs , the present analysis was limited to ecgs with narrow qrs ( qrs duration < 120 ms ) . the qt interval was corrected using bazett 's formula and categorized as normal or abnormal using sexspecific criteria ( men : qt c 430 ms  normal , 431 to 450 ms abnormal ; women : qtc 450 ms  normal , 451 to 470 ms  borderline , > 470 ms pathologic q waves were defined as q waves 40 milliseconds in duration and > 25% of the voltage of the following r wave . q waves were classified according to territory , based on presence in at least 2 contiguous leads , as anterior ( leads v1v5 ) , lateral ( leads i , avl , and v6 ) , and inferior ( leads ii , iii , and avf ) . fqrs was identified as previously defined by the presence of various rsr patterns with or without q wave , including an additional r wave ( r ) , notching of the r wave , notching in the nadir of the s wave , or the presence of more than 1 r ( fragmentation ) in at least 2 contiguous leads corresponding to a major coronary artery territory ( figure 1a and 1b ) . if notching was confined only to the terminal qrs accompanied by j point elevation of 0.1 mv , it was classified as early repolarization pattern rather than fragmentation . fragmentation was classified by anatomic territory , similar to q waves , into anterior ( leads v1v5 ) , lateral ( leads i , avl , and v6 ) , or inferior ( leads ii , iii , and avf ) . ecg assessment for fragmentation and q waves were performed by 2 trained readers blinded to the case / control status of the subjects . the study was approved by the institutional review boards of cedarssinai medical center , oregon health and science university , and all participating hospitals . student t tests and pearson 's  tests were used for comparisons of continuous variables ( presented as meanstandard deviation ) and categorical variables ( presented as numbers and percentages ) , respectively . multivariable logistic regression was used to estimate odds ratios ( or ) for the association of fqrs with scd case status after adjusting for parameters that were significant in the univariate analyses . for the multivariable model , qtc ( as described earlier ) and heart rate ( 100 versus < 100 bpm ) were categorized based on accepted standards . results were reported as 2tailed p values , with a p value of 0.05 being considered statistically significant . all analyses were performed using spss statistical software ( version 20.0 for windows , spss inc , ibm corporation , new york ) . a total of 590 obese / overweight subjects ( 185 cases and 405 controls ) were studied . age , sex , frequency of current / former smokers , and the relative proportions of overweight and obese were not significantly different between case and control groups . severe lv dysfunction ( lvef 35% ; 14.6% versus 4.7% ; p<0.01 ) , diabetes mellitus ( 43.8% versus 29.9% ; p<0.01 ) , and coronary artery disease ( 88.6% versus 77.5% ; p<0.01 ) were all more frequent in cases . use of angiotensinconverting enzyme inhibitors ( acei ) and beta blockers was similar between cases and controls while use of angiotensin receptor blockers ( arbs ) was higher among controls ( 6.8% versus 12.2% , p=0.05 ) . demographic and clinical characteristics of subjects results presented as meansd for continuous variables and n ( % ) for categorical variables . body mass index categories : overweight ( bmi 25 to 29.9 kg / m ) , obese ( bmi30 kg / m ) . left ventricular function categories : ejection fraction ( ef ) 55% ( normal ) , ef 3654% ( mildmoderate dysfunction ) , ef 35% ( severe dysfunction ) ; available for 109 cases and 263 controls . data on use of angiotensin receptor blocker ( arb ) and beta blocker were available for 177 cases and 226 controls . data on use of angiotensin converting enzyme inhibitor ( acei ) were available for 176 cases and 376 controls . scd cases 50 years age assumed to have cad based on > 95% likelihood of cad in such cases . the ecgs were performed a median of 313 days prior to the scd event ( range 2 to 5094 ) , with 75% being performed within 3 years of the scd event . the prevalence of the specified ecg parameters among cases and controls is outlined in table 2 . qrs fragmentation in any territory was detected in 64 ( 34.6% ) cases and 109 ( 26.9% ) controls , with higher prevalence in cases ( p=0.06 ) . when stratified by coronary artery territory , fragmentation was most frequently seen in the inferior territory in cases as well as controls . while there was no significant difference between cases and controls with regard to inferior ( 28.1% versus 23.7% ; p=0.25 ) , and anterior territory fragmentation ( 9.7% versus 5.9% ; p=0.10 ) , lateral fqrs was significantly more likely to be seen in cases compared with controls ( 8.1% versus 2.5% ; p<0.01 ; figure 2 ) cases were also significantly more likely than controls to have fragmentation in 2 or more anatomic territories ( 9.7% versus 4.9% ; p=0.02 ; figure 3 ) . there were 3 ( 1.6% ) cases with fragmentation in all 3 anatomic territories , compared with none in the control group . the frequency of pathologic q waves was not significantly different between cases and controls ( 14.8% versus 10.0% ; p=0.09 ) . electrocardiographic characteristics of cases and controls results presented as n ( % ) .qt interval categories : men 430 ms ( normal ) , 431 to 450 ms ( borderline ) , and > 450 ms ( abnormal ) ; women 450 ms ( normal ) , 451 to 470 ms ( borderline ) , and > 470 ms ( abnormal ) . prevalence of fragmented qrs complexes ( fqrs ) by coronary artery territory in cases and controls . number of anatomic territories with qrs fragmentation in cases and controls . with regard to other ecg parameters , mean heart rate was significantly higher in cases compared with controls ( 77.816.9 versus 68.114.0 bpm ; p<0.01 ) . cases were also more likely to have borderline ( 15.3% versus 9.9% ) or abnormal qtc ( 23.5% versus 7.2% ; both p<0.01 ) compared with controls ( p<0.01 ) . there was no significant difference in qrs duration ( 87.910.1 versus 87.38.3 ; p=0.50 ) . in a multivariable logistic regression model , presence of lateral territory fragmentation was significantly associated with scd ( or=2.84 ; 95% ci 1.01 to 8.02 ; p=0.05 ) after adjustment for covariates significant in the univariate analysis . other significant parameters included severe lv dysfunction ( or=3.55 ; 95% ci 1.54 to 8.21 ; p<0.01 ) , abnormal qtc ( p<0.01 ) , and abnormal heart rate ( p=0.02 ; table 3 ) . severe left ventricular dysfunction defined : ef 35% ; abnormal qt interval categories : men > 450 ms and women > 470 ms ; abnormal heart rate : heart rate > 100 bpm . a total of 590 obese / overweight subjects ( 185 cases and 405 controls ) were studied . age , sex , frequency of current / former smokers , and the relative proportions of overweight and obese were not significantly different between case and control groups . severe lv dysfunction ( lvef 35% ; 14.6% versus 4.7% ; p<0.01 ) , diabetes mellitus ( 43.8% versus 29.9% ; p<0.01 ) , and coronary artery disease ( 88.6% versus 77.5% ; p<0.01 ) were all more frequent in cases . use of angiotensinconverting enzyme inhibitors ( acei ) and beta blockers was similar between cases and controls while use of angiotensin receptor blockers ( arbs ) was higher among controls ( 6.8% versus 12.2% , p=0.05 ) . demographic and clinical characteristics of subjects results presented as meansd for continuous variables and n ( % ) for categorical variables . body mass index categories : overweight ( bmi 25 to 29.9 kg / m ) , obese ( bmi30 kg / m ) . left ventricular function categories : ejection fraction ( ef ) 55% ( normal ) , ef 3654% ( mildmoderate dysfunction ) , ef 35% ( severe dysfunction ) ; available for 109 cases and 263 controls . data on use of angiotensin receptor blocker ( arb ) and beta blocker were available for 177 cases and 226 controls . data on use of angiotensin converting enzyme inhibitor ( acei ) were available for 176 cases and 376 controls . scd cases 50 years age assumed to have cad based on > 95% likelihood of cad in such cases . the ecgs were performed a median of 313 days prior to the scd event ( range 2 to 5094 ) , with 75% being performed within 3 years of the scd event . the prevalence of the specified ecg parameters among cases and controls is outlined in table 2 . qrs fragmentation in any territory was detected in 64 ( 34.6% ) cases and 109 ( 26.9% ) controls , with higher prevalence in cases ( p=0.06 ) . when stratified by coronary artery territory , fragmentation was most frequently seen in the inferior territory in cases as well as controls . while there was no significant difference between cases and controls with regard to inferior ( 28.1% versus 23.7% ; p=0.25 ) , and anterior territory fragmentation ( 9.7% versus 5.9% ; p=0.10 ) , lateral fqrs was significantly more likely to be seen in cases compared with controls ( 8.1% versus 2.5% ; p<0.01 ; figure 2 ) . cases were also significantly more likely than controls to have fragmentation in 2 or more anatomic territories ( 9.7% versus 4.9% ; p=0.02 ; figure 3 ) . there were 3 ( 1.6% ) cases with fragmentation in all 3 anatomic territories , compared with none in the control group . the frequency of pathologic q waves was not significantly different between cases and controls ( 14.8% versus 10.0% ; p=0.09 ) . electrocardiographic characteristics of cases and controls results presented as n ( % ) .qt interval categories : men 430 ms ( normal ) , 431 to 450 ms ( borderline ) , and > 450 ms ( abnormal ) ; women 450 ms ( normal ) , 451 to 470 ms ( borderline ) , and > 470 ms ( abnormal ) . prevalence of fragmented qrs complexes ( fqrs ) by coronary artery territory in cases and controls . number of anatomic territories with qrs fragmentation in cases and controls . with regard to other ecg parameters , mean heart rate was significantly higher in cases compared with controls ( 77.816.9 versus 68.114.0 bpm ; p<0.01 ) . cases were also more likely to have borderline ( 15.3% versus 9.9% ) or abnormal qtc ( 23.5% versus 7.2% ; both p<0.01 ) compared with controls ( p<0.01 ) . there was no significant difference in qrs duration ( 87.910.1 versus 87.38.3 ; p=0.50 ) . in a multivariable logistic regression model , presence of lateral territory fragmentation was significantly associated with scd ( or=2.84 ; 95% ci 1.01 to 8.02 ; p=0.05 ) after adjustment for covariates significant in the univariate analysis . other significant parameters included severe lv dysfunction ( or=3.55 ; 95% ci 1.54 to 8.21 ; p<0.01 ) , abnormal qtc ( p<0.01 ) , and abnormal heart rate ( p=0.02 ; table 3 ) . severe left ventricular dysfunction defined : ef 35% ; abnormal qt interval categories : men > 450 ms and women > 470 ms ; abnormal heart rate : heart rate > 100 bpm . to the best of our knowledge this is the first evaluation of the potential association between qrs fragmentation on ecg and scd , in a communitybased obese / overweight population . the findings of this study could be important both from a mechanistic as well as risk stratification perspective . firstly , there was a higher prevalence of fragmentation overall among scd cases compared with controls . secondly , fragmentation in the lateral coronary territory was significantly associated with increased scd odds even after adjustment for reduced ef and other ecg parameters . thirdly , scd cases were also distinguished by a greater burden of fragmentation in that they were more likely to have fragmentation in 2 or more anatomic territories . increased heart rate and qt interval were also significantly associated with increased scd odds which is consistent with earlier reports . importantly , presence of pathologic q waves was not significantly different between cases and controls in this population . this is in concordance with prior studies which have shown that fragmented qrs complexes are more sensitive at detecting myocardial scar and predict cardiac events even after resolution of q waves . furthermore , since fragmentation , unlike q waves owes its genesis to inhomogeneous myocardial conduction , it may reflect other causes of delayed conduction as well , such as myocardial fatty infiltration , which may be especially relevant in the obese / overweight . in arrhythmogenic right ventricular dysplasia ( arvd ) , characterized by fibrous / fatty replacement of right ventricular myocardium , fqrs has diagnostic value and also predicts arrhythmic events . additionally , the utility of fqrs in conditions such as cardiac amyloidosis supports the concept that fqrs may be a broader marker of myocardial infiltration beyond cadrelated scar . of note reduced lvef , while important , does not encompass the entire spectrum of adverse cardiac remodeling . for instance , fibrosis detected by cardiac magnetic resonance ( cmr ) has been reported to predict scd beyond lvef . in this context , fqrs has been shown to correlate with subclinical lv dysfunction and adverse cardiac events in patients with preserved lvef . it has also been shown to correlate with ventricular dyssynchrony and regression of fqrs with response to cardiac resynchronization therapy . thus , being a more sensitive marker of an adverse myocardial substrate , fqrs may have special relevance for scd risk stratification in the obese / overweight . while the exact pathophysiologic pathways linking obesity to scd remain to be elucidated , it is likely that the deleterious alterations in cardiac structure known to occur in obesity , including ventricular dilatation , cardiac hypertrophy , fibrofatty change , and myocardial lipid accumulation play an important role . such changes may lead to increased cardiac irritability reflected by a greater burden of ventricular ectopy and a greater tendency to develop atrial fibrillation . in this study , conversely , an analysis from the madit ii population reported that inferior fqrs was more predictive of scd . however , the latter study was conducted on a heart failure / defibrillator population , distinct from our evaluation in the general population . another study assessing fragmentation in the general population also reported an association between lateral fqrs and arrhythmic mortality , similar to the present study . it is possible that different patterns of fragmentation may have relevance in different risk groups . additionally , the quantitative burden of fragmentation , reflected by the number of leads with fragmentation , is likely to be important as well . though fqrs appears promising as a risk marker , whether it can be used clinically to aid decision making for primary prevention of scd needs further investigation . while there is accumulating evidence that fqrs predicts both arrhythmic events and appropriate icd shocks , a large multisite study among patients with lvef 35% found no evidence that fqrs would be useful in risk stratifying patients eligible for primary prevention icd . strengths of the present study include its populationbased nature , prospective ascertainment and adjudication of scd cases , as well as availability of detailed lifetime clinical history for both cases and controls . the study was performed on obese / overweight subjects only and may not apply to the overall population . we had to restrict the analysis to those with appropriate ecgs available which could lead to some bias in selecting patients with higher cardiac risk . on the other hand , given the burgeoning obese population and the close association of obesity with cardiovascular risk , this group represents a potentially important target for aggressive prevention . the wide confidence intervals of the effect estimates likely reflect the limited number of subjects ; however , these were identified from a population of approximately 1 million , highlighting the practical difficulties of studying such subjects in the general population . while adjustment for a more comprehensive list of variables could not be carried out , at present ef is the only parameter used for scd risk stratification and fragmentation may help improve risk prediction beyond ef . further studies will be needed to clarify the exact mechanisms linking fragmentation in specific territories to arrhythmogenesis . we could not precisely estimate the prevalence of fragmentation among subjects without cad as a good proportion of cases without previously diagnosed cad may in fact have underlying cad , as has been demonstrated by prior autopsy studies of scd in the general population . finally , further prospective studies assessing the role of fqrs in a variety of highrisk groups in the population will be needed prior to its application in the clinical arena . in this populationbased study among obese / overweight subjects , qrs fragmentation in the lateral territory was associated with increased scd risk even after adjustment for lvef . obese scd subjects were also characterized by a greater likelihood of fragmentation in 2 or more coronary territories . the utility of fragmentation for scd risk stratification in subjects with high bmi warrants further evaluation . the authors would like to acknowledge the significant contribution of american medical response , portland / gresham fire departments , and the oregon state medical examiner 's office .
backgroundobesity has been associated with significantly greater risk of sudden cardiac death ( scd ) ; however , identifying the obese patient at highest risk remains a challenge . 
 we evaluated the association between qrs fragmentation on the 12lead electrocardiogram and scd , in obese / overweight subjects.methods and resultsin the ongoing prospective , communitybased oregon sudden unexpected death study ( population approximately 1 million ) , we performed a casecontrol analysis , comparing obese / overweight scd victims with obese / overweight controls from the same geographic region . 
 archived ecgs prior and unrelated to the scd event were used for cases and all ecg measurements were assessed in blinded fashion . 
 fragmentation was defined as the presence of rsr patterns and/or notching of the r / s wave in at least 2 contiguous leads . 
 analysis was limited to ecgs with qrs duration < 120 ms . 
 overall prevalence of fragmentation was higher in cases ( n=185 ; 64.913.8 years ; 67.0% male ) compared with controls ( n=405 ; 64.911.0 years ; 64.7% male ) ( 34.6% versus 26.9% , p=0.06 ) . 
 lateral fragmentation was significantly more frequent in cases ( 8.1% versus 2.5% ; p<0 . 
 01 ) , with nonsignificant differences in anterior and inferior territories . 
 fragmentation in multiple territories ( 2 ) was also more likely to be observed in cases ( 9.7% versus 4.9% , p=0.02 ) . 
 in multivariable analysis with consideration of established scd risk factors , lateral fragmentation was significantly associated with scd ( or 2.84 ; 95% ci 1.01 to 8.02 ; p=0.05).conclusionqrs fragmentation , especially in the lateral territory is a potential risk marker for scd independent of the ejection fraction , among obese / overweight subjects in the general population .