A Case Control Study of Risk Factors for Coronary Artery Disease in Pakistani Females

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1 A Case Cotrol Study of Risk Factors for Coroary Artery Disease i Pakistai Females Nazeer M., 1 Naveed T., 2 Ama Ullah 3 Address for Correspodece: Dr. Mohsi Nazeer. Assistat Professor Cardiology. Pujab Istitute of Cardiology, Lahore Objectives: To establish the stregth of associatio of covetioal risk factors for coroary artery disease i ative Pakistai females. Methods: We coducted a case cotrol hospital based study o 198 females (age years) scheduled for their first coroary agiography at Pujab Istitute of Cardiology, Lahore. Patiets were divided ito pre-meopausal group (age: 45.1 ± 6.3) ad post-meopausal group (62.1 ± 9.1). For each risk factor, patiets with sigificat CAD ( 50% lumial diameter steosis) were regarded as cases a those without sigificat CAD were take as cotrols. Odds Ratios (OR) ad their 95% cofidece itervals (CI) were calculated by uivariate aalysis. Results: I total study cohort, Diabetes mellitus (OR % CI ), Family history of premature coroary artery disease (OR 2.3, 95% CI ), ad icreased waist circumferece (OR 2.11, 95% CI ) were strogly associated with sigificat CAD. I post meopausal age group, diabetes mellitus (OR 2.66 CI ), hyperlipedemia (OR 2.25 CI ) ad icreased waist circumferece (OR 2.16 CI ) reached statistical sigificace. I pre-meopausal females oly diabetes was strogly associated with sigificat coroary artery disease (OR 10 CI ). Associatio of hypertesio was ot sigificat i ay of subgroups studied. Very few cases of smokig (6 / 198) were foud i our study to merit ay further statistical aalysis. Coclusios: Diabetes mellitus was the oly risk factor i pre-meopausal females associated with coroary artery disease While diabetes, hyperlipedemia ad icreased waist circumferece were sigificatly associated with CAD i post-meopausal females. Key words: Coroary risk factors; pre-meopausal females, post-meopausal females, case cotrol study. Abbreviatios: CAD: coroary artery disease; OR: Odds Ratio; CI: Cofidece Itervals, CABG: coroary artery bypass graftig: QCA: Quatitative coroary agiography. Itroductio Coroary artery disease is the leadig cause of morbidity ad mortality i developed coutries ad is also becomig the leadig cause of death i uderdeveloped coutries world wide. May risk factors, first documeted i males, were also foud to similarly affect females. Hece oce established i a coutry or regio, coroary artery disease affects males ad females equally. 1 Although recet decades have show decreasig CAD related mortality i wester male populatio, death rates have either bee stable or icreased i females. 2,3 I particular, wome youger tha 55 years, have worse progosis after acute myocardial ifarctio tha their male couterparts, with greater recurrece ad higher mortality. 4 Curretly, Idia Subcotiet is experiecig rapid icrease i the rates of CAD. 5 Cosequetly there is a great iterest i clarifyig epidemiology of coroary artery disease i this regio. Various studies have bee carried out i Subcotiet immigrats i developed coutries 6,7 ad locally i idigeous populatio. 8,9 These studies suggest a earlier oset of aggressive coroary artery disease with higher rate of complicatios afterward. Clusterig of risk factors was also commoly foud i Asias. The curret study is a stadardized hospital-based casecotrol study that seeks to defie the stregth of associatio of covetioal coroary risk factors i the agiographically prove cases of females with sigificat coroary artery disease, from a urba commuity of Pujab. Methods This prospective case cotrol study was coducted at Pujab Istitute of Cardiology, Lahore i Pujab Istitute of Cardiology is a dedicated cardiology hospital, servig to both urba ad rural populatio of Pujab. Cases I 2004, durig a period of six moths, 506 cosecutive male ad female patiets udergoig their first diagostic agiography for suspected ischemic heart disease were iterviewed. Study populatio cosisted of 218 female patiets from this cohort. Iformed coset was take from the patiets or their guardia. Twety patiets (9%) declied to be icluded i the study. Remaiig 198 female patiets or their guardias were iterviewed before coroary agiography by a traied doctor. Ay missig iformatio was collected from ANNALS VOL 16. NO. 3 JUL. SEPT

2 NAZEER M., NAVEED T., AMAN ULLAH patiet s charts. All the iformatio was collected o a performa which was completed oce agiographic fidigs were made available. A total of 98 females were foud to have sigificat coroary artery disease ad were regarded as cases. Cotrols Patiets were equired about seve coroary artery disease risk factors. Withi each risk factor group, patiets without sigificat coroary artery disease served as cotrol. Oe hudred such patiets served as cotrols for this study. Exclusio Criteria: Patiets with previous evidece of coroary artery disease like previous myocardial ifarctio, coroary itervetio or CABG were excluded from the study. Patiets who already had coroary agiogram were also excluded. Similarly patiets takig lipid lowerig therapy ad those with valvular heart disease, cardiomyopathies or myocarditis were also excluded. Defiitio of terms: Sigificat coroary artery disease: Fifty percet or more diameter steosis i ay major coroary artery or its major brach (> 2.5 mm) was cosidered as sigificat. Each lesio o coroary agiogram was reviewed by two cardiologists who were blided about the risk profile of the patiet. Each lesio was reviewed i two orthogoal plaes. I case of disagreemet amog cardiologist, QCA usig Philips Xcelera (PIE Medical CAAS 2000) system was performed. Risk Factors Patiets o oral hypoglycemic drugs, Isuli or those havig fastig blood sugar > 126 g/dl were regarded as havig diabetes mellitus. Those with blood pressure > 140 / 90 mmhg take twice or those o atihypertesive drugs were defied as hypertesives. All the patiets had their fastig lipid levels checked oe day before coroary agiography. A diagosis of hyperlipedemia was made if total Cholesterol is > 160 mg/dl, Triglycerides > 150 mg/dl, ad LDL > 130 mg/dl. Waist circumferece was measured by a staff urse at the level of aterior superior iliac spie. A waist circumferece greater tha 35 iches (89 cm) was cosidered abormal. 10 Females with history of ischemic heart disease i first degree male relatives of less tha 55 years or i female relatives less tha 65 years were regarded as havig history of premature coroary artery disease i the family. Meopause was cosidered to be preset whe there was o history of mestrual periods for the last oe year. Curret smokers were defied as those who smoked ay form of tobacco i the previous 6 moths while former smoker were those who had quit more tha 6 moths earlier. History of vascular disease i peripheral limbs, carotid or real, meseteric arterial ivolvemet was defied ad peripheral vascular disease ad cosidered a positive risk factor. Statistical Aalysis Idepedet variables (Risk factors) ad mai outcome variable (Coroary artery disease) were treated as categorical variables. These are represeted by umbers ad percetages. Age was regarded as cotiuous variable ad measure of cetral tedecy was mea ad stadard deviatio. Cases ad cotrols withi each risk factor group were used to calculate Odds Ratio ad their 95% cofidece itervals i uivariate aalysis. Results Betwee February 2004 ad July 2004, a total of 506 patiets udergoig their first coroary agiogram for ischemic heart disease were recruited. This study presets the data of 198 female patiets from this cohort. Depedig upo history of mestrual periods, females were divided ito two groups, post meopausal ad pre-meopausal. Presece or absece of sigificat coroary artery disease was oted for each coroary artery disease risk factor group. Withi each risk factor group, those showig sigificat CAD were regarded as cases while those showig mild coroary artery disease or ormal coroaries were regarded as cotrols. Table 1: Baselie characteristic of study populatio. Total Patiets: 506 Females: 198 Post Meopausal (: 147) Pre Meopausal (: 51) Cliical Presetatio Cases (: 79) Cotrols ( : 68) Cases (: 19) Cotrols ( : 32) Chest pai Acute MI Ustable Agia Cardiac failure Arrhythmias ANNALS VOL 16. NO. 3 JUL. SEPT. 2010

3 A CASE CONTROL STUDY OF RISK FACTORS FOR CORONARY ARTERY DISEASE IN PAKISTANI FEMALES Table 2: Coroary Artery Disease Risk Factors i Study Populatio (: 198). Variable Age Cases / Cotrols (Years ± SD) Total. 198 (%) Post-meopausal. 147 (%) Pre-meopausal.51 (%) 59.2 ± 11.4 / 56.3 ± ± 9.3 / 61.5 ± ± 7.4 / 45.2 ± 5.7 Diabetes Mellitus 94 (49) 73 (50) 21 (43) Hypertesio 66 (34) 51 (35) 15 (29) Hyperlipedemia 102 (53) 72 (50) 30 (59) Waist Circumferece >35 96 (50) 84 (57) 12 (23) Smokig 06 (3) 06 (4) 0 (0) PVD / Stroke 4 (2) 4 (3) 0 (0) SD: Stadard deviatio; CAD: Coroary artery disease; PAD: Peripheral vascular disease Table 3: Clusterig of Risk Factors i Patiets with sigificat Coroary Artery Disease. No of Risk factors Total female Cases (=98) Post-meopausal Cases (=79) Pre-meopausal Cases (=19) Sigle risk factor 17 (17%) 17 (21%) 12 (66%) Two risk factors 60 (60%) 46 (58%) 5 (24%) Three risk factors 23 (23%) 16 (20%) 2 (5%) * Percetages ad umbers were rouded to earest figure Table 4: Associatio of Risk factors with Coroary Artery Disease i Total Female Populatio (: 198) Variables CAD OR (95% CI) P Odds Ratio (95% CI) Diabetes Mellitus (2 6.5) < Family H/O IHD ( ) 0.01 Waist Circumferece >35 cm ( ) 0.01 Hyperlipedemia ( ) 0.08 Hypertesio ( ) ANNALS VOL 16. NO. 3 JUL. SEPT

4 NAZEER M., NAVEED T., AMAN ULLAH Table 5: Associatio of Risk factors with Coroary Artery Disease i Post- Meopausal Female Populatio (: 147). Variables CAD OR (95% CI) P Odds Ratio (95% CI) Diabetes Mellitus ( ) Hyperlipedemia ( ) 0.01 Waist Circumferece >35 cm ( ) 0.02 Family H/O IHD ( ) 0.09 (NS) Hypertesio ( ) 0.36 (NS) Table 6: Associatio of Risk Factors with Coroary Artery Disease i Pre-Meopausal Female Populatio (: 51). Variables CAD Odds Ratio (95% CI) P Diabetes Mellitus ( ) Family H/O IHD (1.0-16) 0.07 (NS) Hyperlipedemia ( ) 0.09 (NS) Hypertesio 15 Waist Circumferece >35 cm ( (NS) ( ) 0.07 (NS) 165 ANNALS VOL 16. NO. 3 JUL. SEPT. 2010

5 A CASE CONTROL STUDY OF RISK FACTORS FOR CORONARY ARTERY DISEASE IN PAKISTANI FEMALES Baselie Characteristics of the Study Groups Table 1 shows the baselie characteristics of the study populatio. Mea age betwee cases ad cotrols withi the two mai groups did ot differ sigificatly, while mea age of pre-meopausal group was 17 years lower tha mea age of post-meopausal group. Majority (62.5%) of post-meopausal females uderwet coroary agiogram due to complait of exertioal chest discomfort. However proportio of patiets with acute myocardial ifarctio ad ustable agia was much higher (25%) i those with sigificat coroary artery disease tha those without (7%). Majority of pre-meopausal females uderwet coroary agiography due to chest pai o exertio. Prevalece of Risk Factors Table 2 shows the prevalece of six mai risk factors for coroary artery disease amog cases ad cotrols of postmeopausal ad pre-meopausal groups. Hyperlipedemia, was the most prevalet risk factor i total female study (53%) populatio as well as i post (50%) ad pre-meopausal (59%) groups. About half of the total female populatio had icreased waist circumferece, however it proportio was low (23%) i pre-meopausal group tha i postmeopausal group (57%). Diabetes mellitus was foud i almost half of the total females ad i both mai groups. Hypertesio was the ext most prevalet risk factor. Predictably very few cases of smokig ad peripheral vascular disease were oted. Table 3 shows that clusterig of risk factors was commo i our study populatio with coroary artery disease. 60% of total female cases had two coroary artery disease risk factors. Same proportio was oted i post meopausal group. Three risk factors were oted i 23% of the total cohort ad 20% of post meopausal group. I pre-meopausal group majority (66%) had sigle coroary risk factor while 24% had two risk factors. Oly few pre-meopausal females had three coroary risk factors. Associatio of Risk Factors with Sigificat Coroary Artery Disease Table 4 shows the overall odds ratios for idividual risk factors i total study populatio. Diabetes mellitus emerged as strogest risk factor (p < ), followed by family H/O ischemic heart disease ad icreased waist circumferece. Hyperlipedemia ad hypertesio, did ot reach statistical sigificace. Table 5 shows Odds Ratios for idividual risk factors i post-meopausal females. Here agai diabetes mellitus showed the strogest associatio with coroary artery disease (p < 0.006). Hyperlipedemia ad icreased waist circumferece were also sigificatly associated with coroary artery disease. I post meopausal females, family history of ischemic heart disease ad hypertesio did ot reach statistical sigificace. Table 6 shows results i pre-meopausal females. Diabetes mellitus was the oly risk factor associated with coroary artery disease i pre-meopausal females. Other risk factors had o statistically sigificat associatio with coroary artery disease i this youg populatio. Discussio The study was desiged to assess the prevalece of covetioal coroary risk factors, ad their stregth of associatio with coroary artery disease i ative female populatio. Diabetes mellitus, hypertesio, hyperlipedemia, icreased waist circumferece ad family history of premature heart disease were aalyzed by uivariate aalysis to assess their stregth of associatio with agiographically prove sigificat CAD. A total of 198 females who were scheduled for coroary agiography due to suspected coroary artery disease, participated i this study. Commo coroary risk factors were oted i all the patiets ad every patiet uderwet coroary agiogram. We divided females ito two groups accordig to their meopausal status istead of groupig by patiet s age. This was doe to clarify the ature of CAD risk factors i youger females of child bearig age. It is ot ucommo these days to see pre-meopausal females admitted with coroary artery disease. However o study i Pakista ad very few i other coutries has studied this segmet of female populatio. We oted high prevalece of coroary artery disease risk factors i our study populatio. Prevalece of diabetes mellitus was aroud 50% i total female ad post-meopausal cohorts ad 43% i pre-meopausal group. Similarly, high prevalece of hyperlipedemia (53%), icreased waist circumferece (50%) ad hypertesio (34%) were oted. This proportio is high if oe cosiders that prevalece of diabetes mellitus i Pakistai females populatio is estimated to be 3.5% ad 2.5% i urba ad rural areas respectively, while prevalece of overall glucose itolerace is 17.5%. 11 Similarly estimated prevalece of hypertesio i adult Pakistai females is 32.7%, Hyperlipedemia i 20.9% ad obesity is estimated to be 22.6%. 12 However this high prevalece of risk factors i female patiets udergoig coroary agiography was also oted i Idia studies. Dave TH et al 13 foud a prevalece of diabetes mellitus as 44.3%, Hyperlipedemia 58%, obesity 58.3% ad hypertesio 52.9% i female populatio udergoig coroary agiography at their ceter. Oomma A et al 14 also cited similarly high prevalece of covetioal risk factors i female populatio scheduled for coroary agiography at their hospital. Clusterig of risk factors was also commo i study populatio. Majority of the total female cases ad postmeopausal females cases had more tha oe coroary artery disease risk factors. I youger females of pre-meopausal group however majority had sigle coroary artery disease risk factor. This high prevalece of risk factors i our study populatio could be due to selectio bias of a hospital based study. But it also reflects high prevalece of multiple risk ANNALS VOL 16. NO. 3 JUL. SEPT

6 NAZEER M., NAVEED T., AMAN ULLAH factors at a youger age i our commuity ad fact that diabetes mellitus is kow cliically to be a strog risk factor of ischemic heart disease i females, leadig to low threshold of ivestigatig chest pai. This study showed a strog associatio of diabetes mellitus, icreased waist circumferece, hyperlipedemia ad family history of IHD with sigificat coroary artery disease. However their relative importace differed i various groups. Diabetes Mellitus was foud to be most strogly associated with CAD i all the three groups. This was particularly so i pre-meopausal age group where it was the oly sigificat risk factor foud. Diabetes elimiates the usual geder gap i CAD mortality ad may iduce accelerated atherogeesis to a greater extet i wome tha i me. 15 Icreased waist circumferece (more tha 35 ) was also sigificatly associated with sigificat coroary artery disease i total female populatio as well as i post-meopausal females. Cutoff poit of 90 cm (35 iches) was chose before lower ethic specific measures for waist circumferece (less tha 80 cm / 31.5 iches) were recommeded by various health advisory groups. 16 This lower cutoff poit would have resulted i more females beig icluded i this risk category. Icreased waist circumferece is oe of the five criteria of uderlyig metabolic sydrome. May of our patiets had clusterig of risk factors costitutig metabolic sydrome, however we did ot evaluated this sydrome as a idepedet coroary artery disease risk factor. Hyperlipedemia showed a statistically sigificat relatioship i post-meopausal females oly. Despite its high prevalece i total female ad pre-meopausal populatio it did ot reach statistical sigificace i these subgroups. LDL ad total cholesterol, as we measured i this study has show modest ad weaker relatioship with coroary artery disease i ative 17 ad immigrat 18 Pakistai populatio. I cotrast, some Idia studies 19 have foud strog relatioship of ambiet lipid levels with sub-cliical atherosclerosis. However modest hyperlipedemia as foud i Ido Pak populatio is ot expected to produce sigificat coroary artery disease i relatively youg pre-meopausal females uless there is some rare heritable defect i hadlig of lipid metabolism. Secodly had we measured HDL levels i patiets, results would have bee more cosistet across the subgroups. Family history of premature coroary artery disease was strogly ad sigificatly associated with sigificat coroary artery disease i our total female cohort. The odds of havig CHD were 2.3 i those who had positive family history of premature CHD i their first degree relatives. However i subgroup aalysis i post ad pre-meopausal females, though it achieved odds of more tha oe, it did ot reached statistical sigificace. Although it is widely regarded as a idepedet risk factor for CAD i multivariate aalysis i several studies, 20,21 it is cotroversial whether family history of premature coroary artery disease act as a idepedet risk factor. I INTERHEART, whe family history was added to the iformatio from other sigificat risk factors, the overall PAR rose from 90.4% to oly 91.4%, idicatig that although family history is a idepedet risk factor for MI, most of the associated risk burde ca be accouted for by other risk factors. 1 Prevalece of hypertesio was betwee 30 ad 40% i total ad both sub-groups. This is cosistet with populatio based studies from this coutry. 12 However it failed to show ay positive statistical relatioship with sigificat coroary artery disease i our study populatio. This discrepacy may be due to high prevalece of hypertesio i our cotrol populatio. Oe reaso for this could well be the stress of ocomig coroary agiography i patiets which admittedly would have affected cotrols more tha cases. Coclusios I this case cotrol study we have show that female Pakistai populatio has high prevalece ad clusterig of traditioal risk factors. This ecessitates itegratig these risk factors ito a global risk score to better predict future coroary evets i the females. Similarly prevetive measures should address ot oly sigle risk factors but should be more ecompassig. Physically active life style to cotrol abdomial obesity ad diabetes, heart healthy diet ad use of statis to cotrol hyperlipedemia should be ecouraged. Every attempt should be made to keep cigarette cosumptio i females at the curret level. These measures are ecoomically feasible i our developig coutry. Limitatios Ideally, to idetify associatio of risk factor to a disease should be doe through a prospective cohort study, but time costrait ad limited resources forced us to choose a hospital based case-cotrol study. Clusterig of risk factors was commo i our study populatio. To mitigate agaist cofoudig effects of multiple risk factors preset i a patiet, logistic regressio aalysis should have bee doe. Additioally socio-ecoomic ad psychological aalysis as a risk factor for CAD should have bee doe, but it was beyod the scope of this study. Fially, the excessively high Odds Ratios ad wide 95% Cofidece itervals oted i pre-meopausal group are probably due to limited umber of cases per risk factor. However our study has show some light o risk factors i this hitherto utouched group i Pakista. A more extesive study i future will be very helpful i resolvig this issue. Refereces 1. Yousef S, Hawke S, Oupuu S, DasT, Avezum A, Laas F et al. 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