because of the significant reduction that has been documented in the progression of atherosclerosis and cardiovascular events through the treatment of dyslipidemia by statins , the non - invasive documentation of atherosclerotic lesions has become an increasingly important target for early treatment and preventive measures ( 13 ) . techniques such as density gradient ultracentrifugation , non - denaturing gradient gel electrophoresis , and nuclear magnetic resonance spectroscopy are available to measure lipid particles to predict the risk of coronary artery disease ( cad ) ; however , these techniques are labor - intensive , technically demanding , expensive , and slow to produce results ( 46 ) . thus , although these techniques are precise and accurate , they are not widely used in clinical settings , and developing surrogate markers of lipid particle profiles is of considerable clinical and economic importance ( 3 ) . the association between the serum levels of total cholesterol and low - density lipoprotein cholesterol ( ldl - c ) in the development of cad has been well established , whereas low serum levels of hdl - c have been considered a major risk factor for chd ( 7 ) . larger , less dense hdl2 particles are considered protective , whereas the smaller , denser hdl3 particles are considered atherogenic ( 8 , 9 ) . the former particles correlate inversely with serum tg levels and small , dense ldl levels ( 10 ) . the tg / hdl - c ratio , which is a relatively novel lipoprotein index indicating the presence of small , dense ldl particles , serves as a potentially significant predictor of cad ( 11 , 12 ) . moreover , it was shown to be one of the non - invasive parameters that are most strongly associated with the extent of coronary disease , as assessed by the friesinger index from conventional coronary angiography ( 13 ) . to the best of our knowledge , despite the growing number of patients diagnosed with cad , no study has reported an association between the lipid parameters , particularly the tg / hdl - c ratio , and extensive cad in mediterranean populations , particularly in cypriots . therefore , the present study was designed to investigate the association between lipid variables , particularly the tg / hdl - c ratio , and the extent and severity of cad in turkish cypriots with suspected cad . a total of 412 consecutive non - diabetic patients with suspected cad ( mean ( sd ) age : 58.8 ( 10.5 ) years , 50.1% male ) who admitted to the hospital between january 2009 and january 2012 who underwent diagnostic coronary angiography upon referral to our cardiovascular laboratory were included in this single - center , cross - sectional study . non - diabetic patients aged 1870 years were included in the study , whereas we excluded patients with co - morbid chronic diseases , concomitant medications affecting carbohydrate metabolism , pregnant patients and turkish patients who were born outside cyprus . there are two major ethnic groups in the island , namely the turkish cypriots who speak turkish and are muslims and the greek cypriots who speak greek and are mostly orthodox christians . written informed consent was obtained from each subject following a detailed explanation of the objectives and protocol of the study , which was conducted in accordance with the ethical principles stated in the  declaration of helsinki  ; this study was approved by the institutional ethics committee . the clinical variables included patient demographics ( age , gender ) , traditional risk factors for atherosclerosis ( such as hypertension , diabetes , smoking , hyperlipidemia , and positive family history ) and the blood biochemistry of the lipid parameters , including total cholesterol , ldl - c , hdl - c , triglycerides and the tg / hdl - c ratio ; these variables were categorized into quartiles . the potential risk factors in the turkish cypriot cohort were also evaluated as predictors of cad in the univariate and multivariate logistic regression models . coronary angiography was performed for the patients with suspected cad , unstable angina pectoris , a positive cardiac stress test , or a history of myocardial infarction . selective coronary cineangiography was performed through the radial or femoral approach using the judkins technique and a general electric angiographic system . multiple views were recorded for all the patients ; the left anterior descending and left circumflex coronary arteries were visualized in at least four views , whereas the right coronary artery was visualized in at least two views . the coronary angiograms were recorded on compact discs in the digital imaging and communications in medicine format . coronary disease severity was assessed by the number of vessels involved ( vessel score ) and by a severity score . target  vessels were those that included target lesions ; all other vessels were designated  non - target  vessels . significant stenosis was determined visually and was defined as a reduction in the lumen diameter by 70% in any view compared to the nearest normal segment . the vessel score ranged from 0 to 3 , depending on the vessels that were involved . the friesinger index is an overall score that ranges from 0 to 15 and is based on the individual scores of each of the three main coronary arteries from 0 to 5 using the following criteria for categorization : 0 , no arteriographic abnormalities ; 1 , trivial irregularities ( lesions with stenosis severity of 129% ) ; 2 , lesions with stenosis severity of 3068% ; 3 , multiple narrowing in the same vessel , with the stenosed segment having either one lesion with a morphology defined as multiple , diffuse , or tubular or two segments having lesions with a stenosis severity of 3068% ; 4 , at least one lesion with a stenosis severity of 69100% , except in the proximal segment in which the severity should be < 100% ; and 5 , the occlusion of the proximal segment of a vessel . patients with scores higher than the cut - off value of 5 were considered to have severe cad ( 3 ) . lesions in the left main cardiac artery were counted as proximal lesions for both the left descending and circumflex arteries . angiographic scoring was performed by two observers who were blinded to the results and clinical data . the traditional risk factors were defined as follow : hypercholesterolemia ( tc > 200 mg / dl ) , hypertriglyceridemia ( > 150 mg / dl ) , high ldl - c ( > 130 mg / dl ) , low hdl - c ( < 40 mg / dl for males and < 50 mg / dl for females ) , elevated tg / hdl - c ratio ( > 4 ) , diabetes mellitus ( fasting glucose 126 mg / dl ) , casual or 2-h ogtt > 200 mg / dl , hypertension ( cutoff points , 140/90 mmhg ) , and being a current smoker . for patients with serum triglyceride levels exceeding 400 mg / dl , a novel method used to estimate ldl - c using an adjustable factor for the tg / vldl - c ratio provided a more accurate guideline for risk classification than the friedewald equation ( 15 ) . the statistical analyses were performed using computer software ( spss version 13.0 , spss inc . the statistical analyses involved a univariate analysis using the chi - square  test and a non - parametric analysis of variance ( anova ; kruskal  wallis test ) followed by a multivariate analysis using stepwise forward logistic regression to assess the independent influence of lipid variables on the extent and severity of cad ( dichotomized by a friesinger index of 5 ) . the data were expressed as the mean ( sd ) , minimum - maximum and percent ( % ) where appropriate . a total of 412 consecutive non - diabetic patients with suspected cad ( mean ( sd ) age : 58.8 ( 10.5 ) years , 50.1% male ) who admitted to the hospital between january 2009 and january 2012 who underwent diagnostic coronary angiography upon referral to our cardiovascular laboratory were included in this single - center , cross - sectional study . non - diabetic patients aged 1870 years were included in the study , whereas we excluded patients with co - morbid chronic diseases , concomitant medications affecting carbohydrate metabolism , pregnant patients and turkish patients who were born outside cyprus . there are two major ethnic groups in the island , namely the turkish cypriots who speak turkish and are muslims and the greek cypriots who speak greek and are mostly orthodox christians . written informed consent was obtained from each subject following a detailed explanation of the objectives and protocol of the study , which was conducted in accordance with the ethical principles stated in the  declaration of helsinki  ; this study was approved by the institutional ethics committee . the clinical variables included patient demographics ( age , gender ) , traditional risk factors for atherosclerosis ( such as hypertension , diabetes , smoking , hyperlipidemia , and positive family history ) and the blood biochemistry of the lipid parameters , including total cholesterol , ldl - c , hdl - c , triglycerides and the tg / hdl - c ratio ; these variables were categorized into quartiles . the potential risk factors in the turkish cypriot cohort were also evaluated as predictors of cad in the univariate and multivariate logistic regression models . coronary angiography was performed for the patients with suspected cad , unstable angina pectoris , a positive cardiac stress test , or a history of myocardial infarction . selective coronary cineangiography was performed through the radial or femoral approach using the judkins technique and a general electric angiographic system . multiple views were recorded for all the patients ; the left anterior descending and left circumflex coronary arteries were visualized in at least four views , whereas the right coronary artery was visualized in at least two views . the coronary angiograms were recorded on compact discs in the digital imaging and communications in medicine format . coronary disease severity was assessed by the number of vessels involved ( vessel score ) and by a severity score . target  vessels were those that included target lesions ; all other vessels were designated  non - target  vessels . significant stenosis was determined visually and was defined as a reduction in the lumen diameter by 70% in any view compared to the nearest normal segment . the vessel score ranged from 0 to 3 , depending on the vessels that were involved . the friesinger index is an overall score that ranges from 0 to 15 and is based on the individual scores of each of the three main coronary arteries from 0 to 5 using the following criteria for categorization : 0 , no arteriographic abnormalities ; 1 , trivial irregularities ( lesions with stenosis severity of 129% ) ; 2 , lesions with stenosis severity of 3068% ; 3 , multiple narrowing in the same vessel , with the stenosed segment having either one lesion with a morphology defined as multiple , diffuse , or tubular or two segments having lesions with a stenosis severity of 3068% ; 4 , at least one lesion with a stenosis severity of 69100% , except in the proximal segment in which the severity should be < 100% ; and 5 , the occlusion of the proximal segment of a vessel . patients with scores higher than the cut - off value of 5 were considered to have severe cad ( 3 ) . lesions in the left main cardiac artery were counted as proximal lesions for both the left descending and circumflex arteries . angiographic scoring was performed by two observers who were blinded to the results and clinical data . the traditional risk factors were defined as follow : hypercholesterolemia ( tc > 200 mg / dl ) , hypertriglyceridemia ( > 150 mg / dl ) , high ldl - c ( > 130 mg / dl ) , low hdl - c ( < 40 mg / dl for males and < 50 mg / dl for females ) , elevated tg / hdl - c ratio ( > 4 ) , diabetes mellitus ( fasting glucose 126 mg / dl ) , casual or 2-h ogtt > 200 mg / dl , hypertension ( cutoff points , 140/90 mmhg ) , and being a current smoker . for patients with serum triglyceride levels exceeding 400 mg / dl , a novel method used to estimate ldl - c using an adjustable factor for the tg / vldl - c ratio provided a more accurate guideline for risk classification than the friedewald equation ( 15 ) the statistical analyses were performed using computer software ( spss version 13.0 , spss inc . the statistical analyses involved a univariate analysis using the chi - square  test and a non - parametric analysis of variance ( anova ; kruskal  wallis test ) followed by a multivariate analysis using stepwise forward logistic regression to assess the independent influence of lipid variables on the extent and severity of cad ( dichotomized by a friesinger index of 5 ) . the data were expressed as the mean ( sd ) , minimum - maximum and percent ( % ) where appropriate . the study sample comprised 412 patients ( mean ( sd ) age : 58.8 ( 10.5 ) years , 50.1% male ) . of the total 412 patients , 44 patients had no coronary lesions , and the remaining 368 patients had cad that ranged from irregularities to total occlusions . the mean ( sd ) friesinger index was 6.9 ( 4.4 ) , and 59.0% of the patients belonged to a friesinger index category of 5 . hypertension ( 75.8% ) , low hdl - c levels ( < 40 mg / dl , 63.6% ) and hypercholesterolemia ( 62.6% ) were the leading comorbidities ( table 1 ) . demographic and clinical characteristics of the study population ( n = 412 ) q14 : lipid quartiles , hdl - c : high density lipoprotein cholesterol the mean ( sd ) serum levels of cholesterol , tg , hdl - c , and ldl - c were 224.9 ( 48.2 ) mg / dl , 177.9 ( 81.7 ) mg / dl , 37.5 ( 12.8 ) mg / dl , and 146.9 ( 35.0 ) mg / dl , respectively , and the mean ( sd ) tg / hdl - c ratio was 5.3 ( 4.2 ) . in the univariate analysis , extensive / severe cad showed a direct relationship with the quartiles of total triglycerides ( 71% of patients with extensive cad were in quartile q4 , whereas 52% were in q1 , p=0.01 ) , and tg / hdl - c ( 72% in q4 vs. 44% in q1 , p=0.001 ) , and an inverse relationship was noted between extensive / severe cad and the hdl - c quartiles ( 73% in q1 vs. 41% in q4 , p=0.001 ) ( table 2 ) . frequency of cad severity according to lipid quartiles in turkish cypriots ( univariate analysis ) ( cad % ) ldl - c : low density lipoprotein cholesterol ; hdl - c : high density lipoprotein cholesterol ; tg : triglycerides ; q14 : lipid quartiles friesenger index : q1 , q2 , q3 , q4 are lipid quartiles / q1 : 0/q2 : 14/q3 : 510/q4 : 1115 in the multivariate model , diabetes ( or , 4.9 ; 95% ci : 1.3  19.2 ; p=0.02 ) and male gender ( or , 3.1 ; 95% ci : 0.95  10.3 ; p=0.06 ) were significantly associated with a higher risk of cad ; likewise a higher triglyceride to hdl ratio was associated with a higher risk of cad , both in the overall study population ( or , 2.2 ; 95% ci : 1.3  3.8 ; p=0.004 ) and in the non - diabetic patients ( or , 1.9 ; 95% ci : 1.4  2.3 ; p=0.003 ) ( table 3 ) . multivariate logistic regression model of risk factors other significant factors from the univariate models : hyperlipidemia , total cholesterol , triglyceride , hdl , daily dietary fat ( marginal ) and age ( marginal ) . hyperlipidemia , total cholesterol , triglyceride , and hdl were not included in the multivariate model because of co - linearity with the triglyceride to hdl ratio . were not significant in the multivariate model . continuous factor where < 25 : 1 , 2530 : 2 , 3035 : 3 , 3540 : 4 , 40 : 5 in the univariate analysis , extensive / severe cad showed a direct relationship with the quartiles of total triglycerides ( 71% of patients with extensive cad were in quartile q4 , whereas 52% were in q1 , p=0.01 ) , and tg / hdl - c ( 72% in q4 vs. 44% in q1 , p=0.001 ) , and an inverse relationship was noted between extensive / severe cad and the hdl - c quartiles ( 73% in q1 vs. 41% in q4 , p=0.001 ) ( table 2 ) . frequency of cad severity according to lipid quartiles in turkish cypriots ( univariate analysis ) ( cad % ) ldl - c : low density lipoprotein cholesterol ; hdl - c : high density lipoprotein cholesterol ; tg : triglycerides ; q14 : lipid quartiles friesenger index : q1 , q2 , q3 , q4 are lipid quartiles / q1 : 0/q2 : 14/q3 : 510/q4 : 1115 in the multivariate model , diabetes ( or , 4.9 ; 95% ci : 1.3  19.2 ; p=0.02 ) and male gender ( or , 3.1 ; 95% ci : 0.95  10.3 ; p=0.06 ) were significantly associated with a higher risk of cad ; likewise a higher triglyceride to hdl ratio was associated with a higher risk of cad , both in the overall study population ( or , 2.2 ; 95% ci : 1.3  3.8 ; p=0.004 ) and in the non - diabetic patients ( or , 1.9 ; 95% ci : 1.4  2.3 ; p=0.003 ) ( table 3 ) . multivariate logistic regression model of risk factors other significant factors from the univariate models : hyperlipidemia , total cholesterol , triglyceride , hdl , daily dietary fat ( marginal ) and age ( marginal ) . hyperlipidemia , total cholesterol , triglyceride , and hdl were not included in the multivariate model because of co - linearity with the triglyceride to hdl ratio . were not significant in the multivariate model . continuous factor where < 25 : 1 , 2530 : 2 , 3035 : 3 , 3540 : 4 , 40 : 5 our findings in a cohort of non - diabetic turkish cypriots with suspected cad revealed a diagnosis of cad in 89.3% of patients and a friesinger index category of 5 in 59.0% of patients . the lipid quartiles showed direct ( tg / hdl - c and triglycerides ) and inverse ( hdl - c ) relationships with extensive / severe cad in the univariate analysis , whereas the presence of co - morbid diabetes , male gender and a high tg / hdl - c ratio ( in non - diabetics ) were significant predictors of a higher cad risk in turkish cypriots . our findings of direct ( tg / hdl - c and triglycerides ) and inverse ( hdl - c ) relationships between lipid quartiles and extensive / severe cad are in agreement with the well - documented correlation between cad and dyslipidemia - related risk factors , such as high triglyceride and ldl levels but low hdl - c levels ( 16,17 ) . the inverse relationship of the hdl - c quartiles with the extent and severity of cad in turkish cypriots supports the data from the lipid research center ( 18 ) and the framingham studies ( 16 ) and emphasizes that lower levels of hdl - c are associated with a higher friesinger index . therefore , a low hdl - c level is an independent risk factor for cad ( 13 , 17 , 18 ) . the tg / hdl - c ratio , which is a relatively novel lipoprotein index , has been considered to indicate the presence of small , dense ldl particles ; thus , it can serve as a good predictor of chd and shows promise as an attractive and powerful surrogate index of the atherogenicity of the plasma lipid profile ( 1113 ) . several studies have attempted to determine whether the tg / hdl - c ratio can function as an atherogenic index to be a highly significant independent predictor of myocardial infarction and whether it is even stronger than the tc / hdl - c and ldl - c / hdlc levels ( 12 ) . accordingly , the identification of the tg / hdl - c ratio as a powerful independent indicator of extensive cad in turkish cypriots with suspected cad is consistent with the consideration of a high tg / hdl - c ratio to predict the extent of cad better than any other lipid parameter , which has been reported in several similar studies conducted in turkish , brazilian and iranian populations and in studies reported by the asia - pacific cohort studies collaboration ( 2 , 3 , 7 , 8 , 11 ) . . showed that a tg / hdl - c ratio of > 4 is the most powerful independent predictor of cad development ( 3 ) . in another study , a tg / hdl - c ratio of 3.5 from a multivariate analysis was reported to be associated with an increased cad burden ( or : 2.87 ; 95% ci : 1.037.96 ; p = 0.04 ) ( 19 ) . the tg / hdl - c ratio was shown to be one of the non - invasive parameters most strongly associated with the extent of coronary disease , as assessed by the friesinger index from conventional coronary angiography ( 13 ) . both insulin resistance and central obesity have been suggested as essential factors for the development of metabolic syndrome and are associated with high tg levels and low hdl levels , which are characteristic features of this syndrome ( 2022 ) . the tg / hdl - c ratio is a good surrogate marker of insulin resistance in the general population worldwide ( 23 ) , except in african americans ( 24 ) . moreover , in premenopausal women , a tg / hdl - c ratio of > 3 is associated with a moderate risk of developing metabolic syndrome ( 25 ) . given the correlation of a low tg / hdl - c ratio primarily with large , non - atherogenic ldl particles and a high tg / hdl - c ratio with a larger population of small , dense , pro - atherogenic ldl particles ( 26 ) , the measurement of the tg / hdl - c ratio should be considered in the risk assessment of chd in individuals with a high prevalence of metabolic syndrome . given that the male gender and co - morbid diabetes were also associated with an increased risk of cad in turkish cypriots , our findings are in agreement with data from previous studies in turkey that demonstrated that in turkish adult males with a high prevalence of metabolic syndrome , low hdl levels and high tg levels were predictive of cardiovascular events ( 27,28 ) . in the framingham study , the risk of cad was reported to be 4.9 times higher in diabetic women and 2.1 times higher in men with diabetes ( 16 ) . for a recent study , increased tg / hdl ratio has been shown association with increased arterial stiffness in apparently healthy individuals ( 29 ) . notably , because 33% of our study population was composed of diabetic patients who have characteristically higher tg / hdl - c ratios , the identification of the tg / hdl - c ratio was one of the significant predictors of cad risk in our study population , even after the exclusion of diabetic patients , indicates the direct association between the tg / hdl - c ratio and extensive cad ; thus , this relationship supports the use of the tg / hdl - c ratio as a surrogate marker in the non - invasive documentation of atherosclerotic lesions in non - diabetic patients . the present study has a number of limitations that should be considered when evaluating the results . first , given the relatively low sample size because of the single - center design , our findings might not be generalizable to the entire cypriot population . second , the cross - sectional design made it impossible to establish any cause and effect relationships . nevertheless , despite these limitations , given the paucity of solid information available on this area and the fact that cyprus is an island nation and a substantial portion of its population are foreign residents , the inclusion of cyprus - born patients with cypriot parents in our cohort represents a valuable contribution to the literature and provides data on the extent and severity of cad using lipid parameters in the turkish cypriot population for the first time . the present study has a number of limitations that should be considered when evaluating the results . first , given the relatively low sample size because of the single - center design , our findings might not be generalizable to the entire cypriot population . second , the cross - sectional design made it impossible to establish any cause and effect relationships . nevertheless , despite these limitations , given the paucity of solid information available on this area and the fact that cyprus is an island nation and a substantial portion of its population are foreign residents , the inclusion of cyprus - born patients with cypriot parents in our cohort represents a valuable contribution to the literature and provides data on the extent and severity of cad using lipid parameters in the turkish cypriot population for the first time . our findings revealed a significant relationship between lipid quartiles and the extent and severity of cad as assessed by the friesinger index . this study also demonstrated significant roles of male gender , co - morbid diabetes and the tg / hdl - c ratio in predicting cad risk among turkish cypriots for the first time in the literature . therefore , in patients with suspected cad , the tg / hdl - c ratio should be used to measure disease severity prior to coronary angiography because it is an easy , noninvasive , and economical method of discerning the extent of coronary atherosclerosis . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .