Open Access Research Journal, www.pieb.cz Medical and Health Science Journal, MHSJ ISSN: 1804-1884 (Print) 1805-5014 (Online) Volume 5, 2011, pp. 10-15 CLINICAL COURSE, MANAGEMENT AND IN-HOSPITAL OUTCOMES OF ACUTE CORONARY SYNDROME IN CENTRAL ASIAN WOMEN The paper describes features history, risk factors and hospital management of acute coronary syndrome (ACS) in women of the Central Asia (829 ACS patients are included), and also comparison of hospital outcomes of ACS in groups of men and women. ACS in women in the Central Asia comprises features as more non Q-wave myocardial infarction frequency, smaller adherence to treatment of dyslipidemia, more obesity degrees. Women arrive to hospital average in 4 hours after men; have more percent of the atypical form. In-hospital outcomes in men and women significantly did not differ because of general tendency to late arriving to the hospital and small quantity of revascularization procedures. The reasons of differences between men and women in the region are mostly connected to social sphere (late arriving, non-treated dyslipidemia) than to physiological peculiarities. ALEKSEY NIKISHIN, RAVSHANBEK KURBANOV, MAHMUDJON PIRNAZAROV Republic Specialized Center of Cardiology, Uzbekistan Keywords: Acute coronary syndrome, in-hospital outcomes, risk factors, central Asian women. UDC: 616.127-005.8-07-055.2-08-036.11-055.1 Introduction Ischemia is known to be the leading cause of women mortality throughout the world. Recent research on emergency cardiology has revealed some peculiar features of the symptoms, course and prognosis of acute coronary syndrome (ACS) in women (Shaw, 2006, Sheifer et al., 2000). It is generally accepted that ACS women are typically elder and, hence, more often have hypertension, diabetes. However, the researches conducted by Vaccarino (1999) and Hochman (1999) have revealed new facts based on analysis of numerous data indicating the difference between males and females in ischemia course that are not related to age. Another axiom of ACS in women postulates on worse inhospital and long-term prognosis, although it was not acknowledged in some research (Alfredsson at al., 2007.). There are data showing that women undergo invasive intervention less often (Rathore et al., 2002); on discharge they receive less evidence-based recommendations; women run higher risk of diabetes mellitus. Thus, the problem of acute coronary syndrome in females has many poorly studied aspects, in Central Asian region in particular. The objectives of the study were to reveal characteristics of history data, clinical course, in-hospital management of acute coronary syndrome in Central Asian women and to compare the in-hospital ACS outcomes in the groups of males and females. Material and methods This study included 829 patients with acute myocardial who were divided into two groups after randomization: group 1 (249patients) - the study group, which included patients of female sex central Asian origin, and group 2 (580 patients) - the control group, which included male patients with acute myocardial infarction. We identified Central Asian patients by their surnames and first names, and by using self-reported ethnicity and country of birth when available. Patients of Caucasian origin were excluded. To evaluate in-hospital outcome, the research involved patients with no age limitation who were admitted with the diagnosis acute myocardial infarction in 2008-2009. The diagnosis was verified according to the WHO criteria. The risk factors, the standard hospital outcomes, - 10 -
and also time characteristics (average arriving-to-hospital time, amount of the patients hospitalized at first 6 hours from ACS onset) were studied. Accumulation and correction of the findings were made using the standard software package of Microsoft Office Access 2003 for Windows XP. Reliability of the indicators difference was evaluated by χ² distribution test. The minimum sufficient significance was Р<0.05. Relative risk (RR) was calculated for each of the factors with 95 confidence interval (CI). Results In accordance with the research protocol, the involved patients were divided into two groups: group 1 included 249 females with acute myocardial infarction (AMI), group 2 was composed of 580 AMI males. Table 1 characterizes the patients and shows that two thirds of them were males (Table 1). TABLE 1. BASELINE CHARACTERISTICS Females Males n n Number 249 30.04 580 69.96 Average age, years 65.0±4.3 60.0±3.7 Weight, kg 78.1±5.4 80.4±6.2 AMI with Q 131 52.61 405 69.83 AMI without Q 118 47.39 175 30.17 Previous MI 55 22.09 135 23.28 Hypertension 129 51.81 232 40.00 Duodenal ulcer 4 1.61 13 2.24 Note: MI-myocardial infarction. The research showed, as expected, that AMI females were elder than males though the age difference was not significant (Р=0.43). Central Asian women, like men, suffered more often from AMI with Q. However, in males, AMI with Q was registered reliably more often (χ 2 =21.9; Р=0.0001). Previous MI (Р=0.78) and duodenal ulcer (Р=0.75) occurred in males and females with equal frequency. The symptoms of hypertension were reliably more often (Р=0.002) registered in females. In-hospital outcomes in the study groups (Table 2) did not differ significantly; they were lethal outcome (OR=1.18; 95 CI 0.62-2.23), recurrent myocardial infarction (OR=0.77; 95 CI 0.46-1.29), recurrent angina pectoris (OR=1.24; 95 CI 0.90-1.72), hemorrhage (OR=0.93; 95 CI 0.29-3.0), congestive heart failure (OR=1.04; 95 CI 0.70-1.54), chronic heart failure (OR=1.75; 95 CI 1.30-2.37). TABLE 2. IN-HOSPITAL OUTCOMES IN THE GROUPS Females n=249 Males n=580 n n Death 15 6.02 30 5.17 Re-infarct 21 8.43 62 10.69 Recurrent angina 78 31.33 156 26.90 Bleeding 4 1.61 10 1.72 Development of acute cardiac failure (Killip classes 2-3) 42 16.87 95 16.38 Development of chronic heart failure 145 58.23 257 44.31-11 -
As the findings show, there were no significant differences between males and females in the depth of affection of the myocardium in AMI (with ECG wave Q); for this reason the criterion, which no doubt influenced the AMI course and prognosis, does not determine reliable gender-difference in the frequency of lethal outcomes in this disease. In our research the women were admitted to the Emergency Unit about four hours later than men (χ 2 =10.8; Р=0.001) that corresponds to the literature data. However, this fact did not impact significantly on the clinical outcomes as only 40-53 patients were admitted in first six hours after the disease onset (Figure1). FIGURE 1. TIME OF PATIENT ADMISSION IN THE STUDY GROUPS 60 53,28 50 40 30 34,68 30,55 40,56 Females 20 Males 10 0 Admission mean time, hr Admitted in first 6 hr, When a coronary attack developed, males were seeking medical aid earlier than females. Thus, every second AMI male was admitted to hospital in first six hours after the attack while only 40.56 females called in a physician in the early hours of the attack. Risk factors and specific therapy in the study groups To study the risk factors a database was formed using the information on 389 AMI patients from 14 hospitals of the region; they included 142 females and 274 males (Table 3). In women compared to men the significant part in the disease prognosis was played by reliably more often occurrence of hypertension (92.25), diabetes mellitus (28.87), dislipidemia (88.73), the untreated one (70.42). It is important that in males, the most significant risk factor is smoking (69.71; Р = 0.0001). Relative risks of stroke, instable angina, disrytnmia and CAFG in women are higher than in men. Both in the females group (χ 2 =13.7; Р = 0.001) and males group (χ 2 =28.9; Р =0.0001), the frequency of cases of treated arterial hypertension was reliably higher than untreated one while dislipidemia in both groups was mainly untreated (females - χ 2 =84.6; Р=0.0001; males - χ 2 =78.6; Р=0.0001). Analysis of the clinical course characteristics showed that relative risk of atypical pain syndrome is 1.6 times higher women than in men (Table 4). The ST segment elevation was found to be reliably more often registered in males (χ 2 =4.11; Р = 0.04). In AMI females, the relative risk of ST segment depression was higher than in males. Mean BP values (148.0 ± 2.94 mm Hg versus 136.5 ± 3.78 mm. Hg in males) and previous MI (29.3 ± 0.15 kg/m 2 versus 27.9 ± 0.21 kg/m 2 in males) were reliably higher in the females. - 12 -
TABLE 3. PAIN THRESHOLD BEFORE STUMP FIXATION Females n=142 Males n=274 Relative risk (95 CI) P Diabetes mellitus 28.87 20.80 1.55 (0.97-2.46) 0.09 Hypertension 92.25 85.04 1.08 (1,04-4.22) 0.05 -Treated 57.04 53.28 0.99 (0.62-1.50) 0.53 -Untreated 35.21 31.75 1,11 (0.76-1.79) 0.55 Dyslipidemia 88.73 80.29 1.11 (1.06-3.52) 0.04 -Treated 18.31 22.99 0.72 (0.38-1.09) 0.33 -Untreated 70.42 57.30 1.23 (1.15-2.73) 0.01 Smoking 7.75 69.71 0.11 (0.02-0.07) 0.0001 Previous MI 38.03 39.78 0.96 (0.61-1.41) 0.81 Ischemic stroke\tia 13.38 7.30 1.83 (1.01-3.81) 0.06 Prev. unstable angina 59.86 54.38 1.10 (0.83-1.89) 0.34 Prev. stable angina 72.54 68.61 1.06 (0.77-1.89) 0.47 CHF 26.76 25.55 1.05 (0.67-1.68) 0.88 Family history CVD 66.90 64.60 1.04 (0.72-1.70) 0.72 Dyshrythmia 22.54 20.44 1.10 (0.69-1.85) 0.14 PAD 2.82 4.01 0.70 (0.22-2.22) 0.73 PCI 2.11 4.74 0.45 (0.12-1.55) 0.29 CABG 2.11 1.82 1.16 (0.27-4.93) 0.86 Note: CHF-chronic heart failure, MI-myocardial infarction, TIA-transient ischemic attack, CVD-cardiovascular disease, PAD-peripheral artery disease, PCI -percutaneous coronary intervention, CABG- coronary artery bypass grafting. TABLE 4. CHARACTERISTICS OF AMI COURSE IN THE STUDY GROUPS Females n=142 Males n=274 Relative risk (95 CI) P Typical pain 87.32 91.97 0.95(0.31-1.16) 0.18 Atypical pain 12.68 8.03 1.58(0.86-3.21) 0.18 Dyspnea 23.24 30.66 0.76(0.43-1.09) 0.14 ST elevated 27.46 37.96 0.72(0.4-0.96) 0.04 ST depressed 33.10 24.82 1.33(0.96-2.34) 0.09 LBBB 4.93 5.47 0.99(0.36-2.25) 0.99 Note: LBBB-left bundle branch block. TABLE 5. THERAPY FOR AMI IN THE STUDY GROUPS Females, n=142 Males, n=274 P UFH 78 54.93 154 56.20 0.89 Dose 18141.0 ± 634.2 18857.1.±.715.8 0.53 LMWH 75 52.82 140 51.09 0.82 Dose 0.47.±.0.01 0.55.±.0.02 0.009* Thrombolysis 4 2.82 10 3.65 0.87 Ca-antagonists 42 29.58 53 19.34 0.02* Nitrates 135 95.07 260 94.89 0.88 Diuretics 101 71.13 147 53.65 0.0001* Beta-blockers 126 88.73 240 87.59 0.86 ACE inhibitors 126 88.73 227 82.85 0.15 ARB 2 1.41 12 4.38 0.19 Antiarrhythmics 23 16.20 35 12.77 0.42 Lipid-lowering 111 78.17 211 77.01 0.88 Insulin 20 14.08 14 5.11 0.003* Oral hypoglycaemic drugs 18 12.68 34 12.41 0.94 Note: *P<0.05; UFH-unfractionated heparin; LMWH-low molecular weight heparin; ARB-angiotensin receptor blocker - 13 -
The comparative analysis of the findings on the therapy prescribed during the patients stay in hospital indicated that females were more often prescribed calcium antagonists than males (χ 2 =4.99), the same was true about diuretics (χ 2 =11.2) and insulin (χ 2 =8.88) (Table 5). However, the doses of low-molecular heparin prescribed to males were reliably higher (Р=0.009). Discussion Most research, being the basis for all guidelines on AMI patient management, was conducted in Western countries (which of course include Australia and New Zealand) that have a number of peculiar features. Are their data comparable with the findings obtained in Central Asian countries having absolutely different social, economic and cultural status? Several studies of this problem have been already conducted, in particular the studies from South Asia (Gupta and Gupta, 1996; Yusuf et al., 1998) as well as reports of Chinese researchers JIANG (Jiang et al., 2006). They demonstrated that inhabitants of Far and Middle East have some peculiar features both in the risk factors prevalence and the AMI clinical course particularly at the level of delivery of health care services. There is almost no information from the region of Central Asia where over 50 million people are living. In our research, we have presented some findings demonstrating the peculiar features of outcomes, risk factors and treatment of AMI in women in Uzbekistan (the Central Asian country of the former Soviet Union) where the situation is, as a whole, similar to that one in neighboring countries (Kyrgyzstan, Turkmenia, Tajikistan and Kazakhstan). More and more information is being published on the fundamental differences in the physiology of sexes besides the reproductive system, these differences are increasing with age. High incidence of hypertension and dyslipidemia draws attention in these data. There is some prevalence of atypical AMI cases that agrees with the findings of some researchers (Hemingway et al., 2008; Volkov et al., 2010; Zaman et al., 2010). Prevalence of atypical complaints of women with ischemia is associated with microvascular and/or angiospastic angina pectoris. It is this pathophysiological mechanism of myocardium ischemia that occurs more often in women than in men population. We believe that later admission of AMI women to hospital is of special importance that probably is associated with both the females physiology (better tolerance of pain syndrome, not evident AMI onset) and social status. Rather low lethality rate attracts attention, too; it is comparable to the global data. However, the rates of MI recurrence and development of relapsing angina pectoris are much higher (except for China). Probably this is also due to late admission of patients and insufficient application of reperfusion techniques. Conclusion The peculiar features of acute myocardial infarction in women living in Central Asia are higher frequency of MI with no Q wave, less compliance with dislipidemia therapy against the background of greater obesity. Women are seeking medical aid four hours later than men; they have a higher percent of atypical MI forms. The main end point, for our opinion, is that reasons of differences between men and women in the region lie mostly in social sphere (late arriving, non-treated dislipidemia and AH) than in physiological peculiarities. In-hospital outcomes in males and females did not differ significantly due to the common tendency to late admission to hospital and a few revascularization interventions. References Alfredsson, J., Stenestrand, U., Wallentin, L., 2007. Gender differences in management and outcome in non- ST-elevation acute coronary syndrome, Heart, Vol.93, pp.1357-362. Gupta, R., Gupta, V., 1996. Meta-analysis of coronary heart disease prevalence in India, Indian Heart J., Vol.48, pp.241-45. - 14 -
Hemingway, H., Langenberg, C., Damant, J., 2008. Prevalence of angina in women versus men a systematic review and meta-analysis of international variations across 31 countries, Circulation, Vol.117, pp.1526-536. Hochman, J., Tamis, J., Thompson, T. et al., 1999. Sex, clinical presentation, and outcome in patients with acute coronary syndromes, N Engl J Med, Vol.341, pp.226-32. Jiang, S., Ji, X., Zhang, C., Wang, X. et al., 2006. Impact of Chinese guidelines for management of patients with acute myocardial infarction on outcomes of hospitalized patients, Chinese Medical Journal, Vol.119(1), pp.26-31 Rathore, S., Wang, Y., Radford, M. et al., 2002. Sex differences in cardiac catheterization after acute myocardial infarction: the role of procedure appropriateness, Ann Iintern Med., Vol.137, pp.487-93. Shaw, L., Bairey, M., Pepine, C. et al., 2006. Insights from the NHLBI-Sponsored Women s Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies, J Am Coll Cardiol., Vol. 47, pp.s4-s20. Sheifer, S., Canos, M., Weinfurt, K., Arora U. et al., 2000. Sex differences in coronary artery size assessed by intravascular ultrasound, Am Heart J., Vol.139, pp.649-53 Vaccarino, V., Parsons, L., Every, N., Barron, H., Krumholz, H., 1999. Sex-based differences in early mortality after myocardial infarction, N Engl J Med., Vol.341, pp.217-25. Volkov, V., Isaeva, A., 2010. Diagnostic and prognostic significance of well-defined evaluation of pain syndrome in women with cardiac ischemia, Liki Ukrainin., Vol.2(138), pp.77-80 Yusuf, S, Ounpuu, S, Anand, S., 1998. Global burden of cardiovascular disease: A review of evidence, in: Coronary Artery Disease in Indians: A Global Perspective, Mumbai: Cardiological Society of India, pp.11-25. Zaman, J., Junghans, C., Sekhri, N., 2008 Presentation of stable angina pectoris among women and South Asian people, CMAJ., 179(7), pp.659-67. - 15 -