GENDER DIFFERENCES IN ISCHEMIC HEART DISEASE AMONG MIDDLE EASTERN POPULATION RAZLIKE MEDJU POLOVIMA KOD ISHEMIJSKE BOLESTI SRCA U POPULACIJI BLISKOG ISTOKA

Background/Aim. In the past three decades, focal segmental glomerulosclerosis (FSGS) was commonly regarded as a part of obesity-related glomerulopathy (ORG), a distinct entity featuring proteinuria, glomerulomegaly, progressive glomerulosclerosis, and a decline of renal function. The present study aimed to evaluate the glomerular morphometry, clinical features, and a two-year outcome in the obese and non-obese FSGS patients. Methods. The study included 35 FSGS patients (23 males, aged 46.5 ? 15.2 years) divided into two groups: obese [body mass index (BMI) ? 27 kg/m2 (18 patients, aged 47.2 ? 15.5 years)] and non-obese [BMI < 27 kg/m2 (17 patients, aged 45.7 ? 15.2 years)]. The serum concentrations of proteins, albumin, cholesterol, tri-glyceride, and creatinine were determined at the time of the biopsy, and 6, 12, and 24 months after the biopsy. Cock-croft-Gault (BMI < 27 kg/m2) and Cockcroft-GaultLBW (BMI ? 27 kg/m2) formulas were calculated. Glomerular radius (GR), glomerular volume (GV), and glomerular density (GD) were compared morphometrically between the two groups. Results. At the time of the kidney biopsy and 6 months later, the obese had significantly lower glomerular filtration rate (GFR) compared to the non-obese. After 24 months of follow-up, there were not any differences between the groups. The obese had a significantly higher GR (109.44 ? 6.03 ?m vs. 98.53 ? 14.38 ?m) and GV (3.13 ? 0.49 ? 106 ?m3 vs. 2.26 ? 0.83 ? 106 ?m3), and only slightly lower GD (1.91 ? 0.39/mm2 vs. 1.95 ? 0.61/mm2) compared to the non-obese. A significant positive association between GV and BMI (r = 0.439) was found. After 12 months of follow-up, a significantly higher percentage of the non-obese patients reached complete remission compared to the obese (71.4% vs. 37.5%, respectively; p = 0.041), but after 24 months there were no significant differences. Conclusion. Obese patients, at the time of the kidney biopsy and 6 months later, had already a significantly lower kidney function compared to the non-obese ones. However, 12 and 24 months after, this difference was not statistically significant. Also, 24 months after, there was no significant difference between the two groups in the percentage of patients with complete remission of the nephrotic syndrome.


Introduction
Ischemic heart disease(IHD) is the most common cause of morbidity and mortality worldwide.(1)Chestpain is a common presentation of acute coronary syndrome (ACS), however, women tend to have more atypical symptoms.(2,3)Studies have shown that men presented more with ST-elevation myocardial infarction (STEMI), where as women presented more with non-STEMI.(4)Symptomatic women undergoing coronary angiography (CA) tend to have less extensive and severe coronary artery disease (CAD), but more adverse prognosis compared to men.(4) The sex differences in mortality after reperfusion are predominantly explained by baseline differences, including advanced age and greater comorbidity in women.Procedural success in percutaneous coronary intervention (PCI) is similar in men and women, although women tend to experience more bleeding complications.(5)Women also face a higher mortality from IHD due to their relatively higher prevalence of "female-pattern" ischemic heart disease.(6) Application of guidelines therapy is improving outcomes in women.However, mechanisms and interventions directed at sex differences in IHD still an area of debate.(7) In this prospectively designed study, we used CA data registry to study the gender-based differences among middle-eastern population presented with IHD in tertiary interventional cardiac center.

Methods
The study was designed as a prospective observational cohort study.We enrolled study subjects with ACS, referred to the Chest Diseases Hospital (CDH) from public sector (Ministry of Health hospitals) as well as private hospitals, for an indicated cardiac CA with possible PCI if needed.(8) Study Subjects and Data Collection Study subjects were prospectively enrolled from 1 st Sep.2014 to 1 st Sep.2015.Inclusion criteria include any patients with age >18 years with IHD diagnosis.IHD diagnosis including both stable and ACS variables were based on the American College of Cardiology clinical data standards.Briefly, stable IHD (SIHD) who have unacceptable ischemic symptoms despite medical therapy and who are amenable to, and candidates for, coronary revascularization, or whose clinical characteristics and results of noninvasive testing (exclusive of stress testing) indicate a high likelihood of severe IHD and who are amenable to, and candidates for, coronary revascularization.In addition those who cannot undergo diagnostic stress testing, or have indeterminate or non-diagnostic stress tests, when there is a high likelihood that the findings will result in important changes to therapy.(9) ACS was defined as a clinical presentation consistent with unstable angina(UA)/NSTEMI or STEMI within 8 days of admission, associated with any one of the following (ECG changes, elevated biomarkers of myocardial necrosis (Any one of CPK-MB/Troponin-T or Troponin-I).STEMI was diagnosed if ECG showed evidence of ST segment elevation in ≥ 2 contiguous leads or a new left bundle brunch block in addition to chest pain or elevated cardiac markers.The rest of the cases were labeled as NSTEMI/UA based on the presence of elevated biomarkers of myocardial necrosis with or without chest pain.
The study protocol was approved by the institutional review board, and all patients provided written informed consent, which included consent for the CA.We exclu edpatients with age < 18 years and patients refusing to give consent.

Statistical methods
Demographic and baseline characteristics, treatment patterns, angiographic status, and inhospital outcomes were compared between men and women overall and according to ACS status: UA/NSTEMI and STEMI.Because patients often had multiple lesions intervened upon during a single PCI laboratory visit, lesion characteristics were assigned as follows: for each characteristic, the highest risk value of any lesion intervened upon during the index PCI was recorded.Continuous variables are described as medians (with inter-quartile ranges) and categorical variables are described as frequencies.Continuous and ordinal categorical variables were compared using stratum adjusted Wilcoxon rank sum tests, whereas nominal categorical variables were compared using stratum adjusted χ2 tests where stratification is by hospital.User-defined missing values are treated as missing.In examining the relationship between gender and outcomes, as well as gender and medical treatments, we initially performed comparisons adjusting for ACS status alone.A P value of 0.05 was established as the level of statistical significance for all tests.All analyses were performed using SAS software (versions 8.2, SAS Institute, Cary, NC).

Baseline demographics and clinical characteristics
A total of 400 IHD patients had completed coronary angiographic data.Mean age was 61 ± 12 years and 64% were males.About70% of the patients was diagnosed with ACS and 30% was diagnosed with SIHD.Females were much older (64±12 vs 59 ± 13, p 0.004) and had higher body mass index (34 ± 7 vs 29 ± 5, p <0.001) in compare to males.Females tend to have more adverse risk factors, hypertension was diagnosed in (87% vs 62%, p <0.001) and diabetes mellitus was diagnosed in (76% vs 58%, p <0.001) in compares to males.(Table 1&2 and Figure 1)

Discussion
Techniques of treatment should be custom designed as per gender, as our registry revealed lesser high-risk angiographic features, but more in-hospital complication rates in females as compared to males.This should not only be instrumental in reducing post-intervention complications, but also shall aid to improve the appropriate antiplatelet therapy adherence and efficacy.In our study, patients were admitted to general hospitals for non invasive cardiology services, this indicates the low referral rates for invasive strategy.The same is in harmony with a results of a recent ACS registry published in Kuwait which shows the rates of inhospital coronary angiography cases as significantly lower (21% for NSTEMI, 17% for STEMI, and 15% for UA (10)) as compared to the Global Registry of Acute Coronary Events (GRACE) rate of 53% for NSTEMI, 55% for STEMI, and 42% for UA.(11) In Kuwait, there was an acute lack of onsite cardiac cath-labs in general hospitals, which was stretching the capacity of the sole invasive cardiac centre which was our site.This might have been a major cause for the less number of in-hospital coronary angiograms, the theory which was also proposed worldwide by Fox KA, Goodman SG, Klein W et al (10).In addition, there are maybe many intrinsic biological mechanisms that need more studies, specifically in the basic level.The rate of women presenting with UA/NSTEMI and that too atypical symptoms were significantly more than men, which was similar to the findings in GUSTO IIb study which attributed this to the differences in anatomy, pathophysiology of CAD, and clinical characteristics in the two genders.(12) However, we feel that this might also have been due to lesser utilization of acute antiplatelet therapy on admission in females, due to unnoticed reasons, eventhough it was proven in other trials (12,13) as well as ours that women with ACS are older and have more co-morbidities.However, as opposed to the findings of Blomkalns AL, Chen AY, Hochman JS et al ( 14) that women with ACS present more often with both prior and current signs of Congestive Heart Failure, we found similar or better left ventricular functions in terms of Ejection Fraction (EF) in women.Chest pain was not a common finding in elderly males/ females, and if found were milder or more often absent in females than their male counterpart-possibly owing to the higher comorbidities like Diabetes Mellitus.However, even though the chest-pain incidences were predominant in many cases of those below the age of 55 years, regardless of the type of ACS, women in the same group seemed to have higher asymptomatic presentation rates.
(3) Eventhough there were high similarities between our patient cohort and those of the Euro Heart Survey II (15), our survey into the treatment and short-term prognosis revealed some noticeable differences (Table 4).Discharge medication rates were similar in both (except that we had 99.6% ASA adherence as opposed to the 95% in Euro Heart Survey II).In hospital heparin administration varied (as it is expected to be given in the first 48 hours, those who were referred to us after more than a week didn't require the same).Even though women mostly presented with atypical cases, and Killip I (as against Killip III for males), and were mostly diagnosed as NSTEMI, most males could be managed by PCI while women had higher CABG rates.Given the information that the results of PCI maybe inferior to CABG, most subjects did not defer from choosing PCI over surgery.The higher mortality rates post-PCI in females have been going down (16)(17)(18)(19), and as per the National Heart, Lung and Blood Institute registries have stooped from 2.6% in 1985 to 1.5% in 1994, p value not significant (20) Variations in procedural outcomes owing to differences from presentation, diagnosis, management and treatment in the two genders were identified by us.However, more work needs to be done to identify and explain these based on inherent biological differences between males and females.(21)

Conclusion
In this single-centre cohort study, we found that among middle-eastern population, females tend to have more adverse risk factors, presented more with non-STEMI, and had fewer rates of in-hospital complications than males.