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AMI in very young (aged ≤ 35 years) Bangladeshi patients: Risk factors & coronary angiographic profile
Clinical Trials and Regulatory Science in Cardiology 13 (2016) 1–5
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AMI in very young (aged ≤ 35 years) Bangladeshi patients: Risk factors & coronary angiographic profile Fazila-Tun-Nesa Malik ⁎, Md. Kalimuddin, Nazir Ahmed, Mohammad Badiuzzzaman, Mir Nesaruddin Ahmed, Ashok Dutta, Dhiman Banik, Md. Kabiruzzaman, Habibur Rahman, Tawfiq Shahriar Huq, Md. Farhad Jamal National Heart Foundation Hospital & Research Institute, Dhaka, Bangladesh
a r t i c l e
i n f o
Article history: Received 19 October 2015 Accepted 8 November 2015 Available online 11 November 2015 Keywords: Acute myocardial infarction Very young adults Risk factor Angiographic profile
a b s t r a c t Background: Coronary artery disease is a devastating disease precisely because an otherwise healthy person in the prime of life may die or become disabled without warning. When the afflicted individual is under the age of 35, the tragic consequences for family, friends, and occupation are particularly catastrophic and unexpected. The purpose of the present study was to assess the risk factors, angiographic profile, and in-hospital outcome of very young patients (aged ≤35 years) with first acute myocardial infarction (AMI). Methods: A cross-sectional study was conducted involving 266 young (≤35 years) patients with clinical diagnosis of AMI. They were studied for risk factors, clinical characteristics, and in-hospital outcome between February 2012 and October 2014 at the NHFH&RI, Dhaka, Bangladesh. Coronary angiography was done in 230 patients. Results: The mean age of patients was 31.19 ± 3.81 years; 94.7% were male. The major risk factor was smoking, followed by dyslipidemia, family history of ischemic heart disease. The most common anatomical location for the MI was the anterior wall. Significant coronary artery disease was found in 83.04% patients, 7.39% patients had normal coronaries. Most patients had single vessel disease followed by double-vessel disease. Left anterior descending was the commonest vessel involved followed by left circumflex artery. In-hospital mortality was 2.3%. Conclusion: AMI in very young almost exclusively occurs in male and smoking was the most common risk factor. Acute anterior MI owing to occluded left anterior descending artery was more frequent. Very young patients with an AMI have a favorable in-hospital mortality. © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Prior to World War II coronary artery disease in men under 30 years of age was regarded as rare, and in men between 30 and 40 years of age, as uncommon [1]. However, acute myocardial infarction (AMI) has been recognized in the young age groups more frequently in recent years [2]. Additionally, AMI in very young patients aged ≤35 years has been poorly described. It is estimated that less than 2% of all AMIs are patients aged ≤35 years [3]. The prevalence of CAD as well as AMI has progressively increased in Bangladesh during the beginning of the century, particularly among the very young urban population. The conventional risk factors do not fully explain the vulnerability of Bangladeshi community to coronary atherosclerosis. Hypertriglyceridemia, low levels of HDL-C, central obesity, high lipoprotein-a (Lp-a), high LDL-C, rising affluence, dietary habits, and rapid modernization associated with sedentary but stressful lifestyle in summation are suggested as additional risk factors for CAD. Apart from smoking, in addition, a subset of ST-segment elevation ⁎ Corresponding author. E-mail address: [email protected] (F.-T.-N. Malik).
myocardial infarction in the very young (≤35 years) is likely related to illicit drug use [4,5] or to nontraditional risk factors, such as oral contraceptive use [6]. Very young patients with ST-segment elevation myocardial infarction are likely to attribute chest pain to other causes and present late. In addition, physicians taking care of such patients also are less likely to consider cardiac cause for such pain in the very young, resulting in withholding of care, inadequate care, or delays in care. The pattern of care and outcomes of the very young with ST-segment elevation myocardial infarction is therefore not well defined [7]. Coronary angiography (CAG) performed in young patients with acute myocardial infarction has identified a relatively high incidence of normal coronary arteries, non-obstructive stenosis or single-vessel disease [8–10]. Very young patients seem to have lower morbidity, with the same mortality [11]. There is a dearth of available data concerning the risk factors, clinical features, coronary angiographic findings, natural history, and prognosis on very young adults with ST-segment elevation myocardial infarction (STEMI), as a life-threatening cardiac emergency condition. No study has been conducted in Bangladesh regarding angiographic characteristics of very young patients with STEMI. So, this study was conducted
http://dx.doi.org/10.1016/j.ctrsc.2015.11.003 2405-5875/© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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to learn the profile of very young patients (≤35 years) with acute myocardial infarction with an emphasis on: assessment of the risk factors; mode of presentation; coronary angiographic characterization and inhospital outcome. 2. Method The approval of the ethics committee of National Heart Foundation Hospital & Research Institute (NHFH & RI) was obtained. This study was conducted at NHFH & RI, Dhaka, Bangladesh from February 2012 to October 2014. All patients aged ≤35 years with first STEMI were included in the study. Patients with previous myocardial infarction, history of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) were excluded from the study. This was a cross-sectional study (case series) which enrolled 266 consecutive patients who fell into the inclusion criteria during this index period. We defined very young age as ≤35 years, definition that is similar to those used by others [1,5,7,11–18]. The risk factors which were studied were hypertension, diabetes mellitus, smoking habits, obesity (a BMI of N25 kg/m2), dyslipidemia, and a family history of ischemic heart disease. Current smokers were defined as individuals who smoked cigarettes in the previous 12 months. Individuals who had quit smoking more than a year earlier were classified as former smokers [19]. Participants were classified as physically active if they reported moderate (walking, cycling) or strenuous exercise (jogging, football, vigorous swimming) for 4 or more hours per week [19]. Coronary angiography was performed in 230 patients out of 266 to assess the number and type of vessels which were involved and percentage of lesion. Significant coronary disease was defined as at least a 70% reduction in the internal diameter of the right, left anterior descending or left circumflex coronary arteries and their branches, or ≥50% reduction in the internal diameter of the left main coronary artery. Moderate disease was defined as 50% to 69% stenosis of major coronary artery segments, 70% to 100% of minor segments or 30% to 49% of the left main coronary. Minimal disease was defined as less coronary obstruction than that for moderate disease. Angiographically normal coronaries had no appreciable stenoses. In the present analysis, patients with minimal or moderate disease were combined and classified as having nonobstructive disease [13]. 2.1. Statistical analysis The collected data were checked and coded manually and then entered into a computer database. The numerical data obtained from the study were analyzed. Data were expressed in frequency, percentage, mean and standard deviation as applicable. Data were analyzed by using computer based SPSS program version 16 for statistical analysis.
Table 1 Baseline characteristics of the patients (n = 266). Variables
Number (%)
Age (years) Sex (M/F) Urban Traditional risk factors: Smoking Hypertension Diabetes Dyslipidemia Family H/O IHD Obesity Other risk factors: Hyper-homocysteinemia(n = 106) Physical inactivity Substance abuse — amphetamine Substance abuse — cannabis Excessive fatty food consumption Energy drink abuse Inadequate vegetable intake
31.19 ± 3.81 252/14(94.7/5.3) 185(69.5) 206(77.4) 57(21.4) 45(16.9) 187(70.3) 126(47.4) 89(33.5) 62(58.5) 147(55.3) 14(5.3) 10(3.8) 127(47.7) 76(27.1) 103(38.7)
measured in 106 patients. Hyper-homocysteinemia was present in 62 (58.5%) patients. Physical inactivity was present in 55.3% patients and obesity in 33.5% patients. 47.7% patients had history of increased fatty food consumption. Substance abuse is very rare: Amphetamine — 5.3%; cannabis — 3.8% and energy drink 27.1%. Oral contraceptive drugs were used by 8 women (57.14%) out of 14. Two female were unmarried. The most common symptom was chest pain, which was present in 95.5% of the patients with radiation of pain (59.8%), followed by sweating (87.6%), nausea/vomiting 36.5% breathlessness (6.4%), and palpitations (3.8%). Twelve patients (4.5%) had atypical symptoms. Two patients complained only of severe weakness and 10 patients had pain either in left hand or in both hands. In our 266 patients, 88 (33.1%) experienced chest pains prior to their MI. Fifty two patients reported nonspecific chest pain and only 36(13.53%) gave a typical history of angina pectoris. The mean time of presentation after the onset of the symptoms was 12.25 ± 1.26 h. Anterior wall MI was found in 56.5% of the patients; 41.6% of them had inferior wall MI; 1.5% lateral wall MI and 0.4% (1) anterior & inferior. AMI was common among B, O, A and AB blood groups, respectively. Angiographic procedures were carried out in 230 patients (86.46%). The remaining 30 patients refused the procedure and 6 patients died before the angiographic study. The left anterior descending artery was infarct related artery (IRA) in 53.91% patients, right coronary artery in 11.31% and the left circumflex coronary artery in 27.39% patients, which was seen on coronary angiography (Table 3). A majority of the patients (68.27%) had single vessel disease which was seen on coronary angiography, followed by double vessel disease (18.69%). 7.39% had normal coronaries, 5.65% had multi vessel disease and 1.73% had left main disease. 7.39% patients had normal coronaries,
3. Results The mean age of the patients were 31.19 ± 3.81 years, with a maximum number of patients (62.8%) being within the age of 31–35 years and 3% of the patients being in the age group of ≤20 years. The frequency of AMI increased with age. The youngest patient was age 17.5 years old and the oldest was 35 years old. 94.7% of the patients were males. Baseline and clinical characteristics of patients are shown in Tables 1 & 2. Most of the patients were service holder (48.9%) followed by businessman (33.8%). AMI in very young patients was highly prevalent in urban population (69.5%). Smoking was most common risk factor for myocardial infarction (77.4%) in the young adults, hyperlipidemia being the second common risk factor (70.3%). 47.4% of the patients had a family history of ischemic heart disease (IHD). The incidence of hypertension (21.4%) and diabetes (16.9%) was very low among the patients. Homocysteine level was
Table 2 Clinical characteristics of the patients (n = 266). Variables Clinical presentation: Chest pain Shortness of breath Nausea/Vomiting Sweating Palpitation Atypical presentation Site of AMI: Anterior Inferior Lateral Anterior & inferior
Number (%) 254 (95.5) 17 (6.4) 97 (36.5) 233 (87.6) 10 (3.8) 12 (4.5) 150 (56.5) 111 (41.6) 4 (1.5) 1 (0.4)
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83.04% patients had significant CAD and 9.57% patients had nonobstructive disease. Of the 266 very young patients with AMI, 123 (46.24%) received intravenous lytic therapy (streptokinase). Primary PCI was performed in fifteen (5.6%) patients, lytic therapy & PCI in 40 (15%), and coronary angioplasty in fifty one (19.2%). There were no deaths during interventional procedures. The remaining patients were treated medically. In addition, we evaluated the in-hospital outcome of these patients, which included symptom-free discharge from hospital, post MI angina, heart failure, post MI arrhythmia, mitral regurgitation, cardiogenic shock cardiac arrest survivors and in-hospital mortality (Table 4). Seventy seven (28.9%) patients developed complications during the acute MI phase. Four (1.6%) of them had persistent chest pain, 27 (10.2%) developed heart failure. Heart failure was classified into four categories according to Killip classification. Killip II was found in 10(3.8%) patients, Killip III was found in 9 (3.4%) patients and Killip IV was found in 8 (3.0%) patients. Thirteen (5.2%) patients had severe rhythm disturbances — atrial fibrillation (1.2%), ventricular tachycardia (3.6%) or ventricular fibrillation 0.4%). Twelve (4.5%) patients had cardiogenic shock. Regarding AV block, I° AV Block was found in 2(0.8%) patients; II° AV Block was found in 3 (1.2%) patients and complete heart block (CHB) was found in 3 (1.2%) patients. Mitral regurgitation (MR) was found echocardiographically in 43 (16.2%) patients. Thirty seven (13.9%) patients developed mild MR and 6(2.4%) patients moderate MR. Three (1.2%) patients were survivors of cardiac arrest. Inhospital mortality occurred in 6 (2.4%). All six patients had extensive anterior AMI and cardiogenic shock. Five of them developed acute left ventricular failure. Three of these six patients had ventricular tachycardia and one complete heart block. Two of them had persistent chest pain. Three patients were thrombolysed with streptokinase. All patients had moderate left ventricular systolic dysfunction (five had EF ≤ 35% and one had 42%). 4. Discussion Coronary atherosclerosis begins early in life, but acute STEMI in adults aged ≤35 years are exceptional. In the past, various mechanisms have been studied; such as rupture of a vulnerable plaque or erosion of the endothelial layer, hypercoagulable states, coronary artery spasm, and inflammation, with atherosclerosis remaining the major cause [3]. Atherosclerotic course begins at birth and considerable lesions in coronary arteries may be apparent as early as the age of 25 or 30 years [20, 21]. The reasons for such brisk progression of atherosclerosis, leading to MI at an early age are still being investigated. Autopsy studies in youth showed a strong relationship involving the degree of atherosclerosis in the coronary arteries with LDL-cholesterol levels, smoking status, blood pressure, and body mass index, and this association was more striking when there was a clustering of the above mentioned risk factors [22]. The distribution of the ages of our patients showed a striking increase of the disease with ageing, which was a very obvious fact and was seen in earlier studies also [23,24].
Table 3 Coronary angiographic characteristics of the patients (n = 230). Variables Infarct related artery: Normal LAD LCX RCA Number of involved vessel: Normal SVD DVD TVD Left main disease
Number (%) 17 (7.39) 124 (53.91) 63 (27.39) 26 (11.31) 17 (7.39) 157 (68.27) 43 (18.69) 13 (5.65) 4 (1.73)
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Table 4 In-hospital outcome of the patients (n = 266). Variables
Number (%)
Persistent chest pain Heart failure AV block Arrhythmia Mitral regurgitation Cardiogenic shock Survivor of cardiac arrest Death
4 (1.6) 27 (10.2) 8 (3.2) 13 (5.2) 43 (16.2) 12 (4.8) 3 (1.2) 6 (2.4)
One of the best documented and the most consistent risk factors for coronary atherosclerosis seems to be the male sex. The protective effects of estrogens in preventing atherosclerosis have been clearly demonstrated in epidemiologic studies [25]. In one study [9], a profile of acute MI in young patients showed a male: female ratio of 20:1, which consistent with our study (19:1); other studies showed reduced ratio (10.1:1) [11]; 7.7:1 [12]; 5:1 [15]; 12.5:1 [16] and 9:1 [23], but the trend remains the same. Among the many factors that have been shown to be important are cigarette smoking, hyperlipidemia, family history of IHD, hypertension, the male sex and diabetes mellitus. These have generally been associated with an increased incidence of fibrous plaques and their sequelae. The associations are relatively strong and they are made on a group comparison basis, although all the studies have demonstrated a high degree of variability among individuals within even the most homogenous of groups [26]. Cigarette smoking is a well-known risk factor for the development of coronary artery disease in young patients. Numerous studies have highlighted elevated rates of tobacco use among very young patients who present with AMI, with percentages ranging from 62 to 90% [11– 13,15,17,27–29]. In agreement with previous reports, our study confirmed that cigarette smoking (77.4%) is one of the major risk factors. Smoking adversely affects all phases of atherosclerosis given that it hastens thrombotic process, instigates endothelial dysfunction, augments proinflammatory effects, and induces coronary vasoconstriction even in patients with normal coronary vasculature [29]. The results of the Lipid Research Clinics Trail [30,31] demonstrated a direct association between the plasma lipoprotein profile, the cholesterol levels and the morbidity and mortality from coronary atherosclerosis. Hyperlipidemia, which is very common in young Asian adults as per earlier studies [6,30–36], was the second common risk factor in our study. Diabetes and hypertension were less common in very young adults in our study, which was seen in earlier studies also [11–13,15,17,27– 29]. In our study 47.4% of patients had a positive family history of IHD which consistent with other studies [12–13,28,36]. In contrast to our study, some other studies showed low incidence of positive family history of IHD [11,15,17,27,29]. Obesity was the infrequent cause in all the earlier studies 3.3–20% [12, 17,29] but in our study it was 33.5%. In the present study, the hyperhomocysteinemia rate in patients with AMI was 58.5%, which was consistent with study done by Masoomi et al. [37], 49.4%. These observations are important for primary prevention of AMI in Bangladesh. The mechanisms that may explain how homocysteine can increase the risk of AMI include its effect on the vascular endothelium, platelets and its role in increasing the risk of thrombosis [38,39]. Physical inactivity was present in 53.5% patients. Chest pain was the most common presentation in our study, which was similar to earlier studies also [23,27,28,40]. The arrival of the patients at the health care facility was mostly delayed by N10 h, as seen in earlier studies also [41–43]. We too had a mean arrival time of 12.25 h. Alizadeasl et al. [44] in their study of ABO blood groups relation and AMI indicated that the incidence of ischemic heart disease was higher in subjects of blood group A or its subgroups. AMI was higher
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among A, then it was common among O, B and AB blood groups, respectively (A N O N B N AB) [11]. In contrast to these two studies the incidence of ischemic heart disease was higher in subjects of blood group B in our study. As in earlier studies [15,17,23,29], in our study too, anterior wall MI was very common among the patients aged ≤ 35 years. In contrast to our study, other authors [11,27] showed inferior wall MI (52% vs 45% and 40% vs 33.3%) as common location. Not much literature is available with respect to angiographic features in very young patients undergoing CAG, and when available they represent only a very small percentage of total population of young patients with CAD. Regarding the extent of coronary lesions, our cases showed a less evolved disease. As described in the literature, young adults are characterized by a less extensive coronary disease, mainly as one-vessel form. The less extensive coronary artery disease and high prevalence of complex lesions observed in young patients might suggest that premature coronary artery disease is associated with rapid disease progression rather than with a gradually evolving process [45]. We could see that single vessel disease was evidently more common among the young adults, which had been reported by others also earlier [13,15–17,23,28,29,46]. Gotsman et al., showed 53% patients had normal coronary arteries [27], which could be due to the small sample size, leading to an overestimation. In the study by Alizadehasl et al., forty three percent patients had normal coronary arteries [11], followed by SVD (30.1%). Wolfe et al. [12] from the USA analyzed angiographic features in 35 patients who were b35 years of age (1.5% of the total number catheterized). They were compared with 100 patients ≥ 55 years of age. They found a very low prevalence of triple-vessel CAD in the first group (14.3%) as compared to 43% in the second group. In the study by Glover et al. [47], 120 consecutive patients 35 years or younger underwent coronary angiography following a clinical MI. Significant CAD was seen in 78% and the prevalence of triple-vessel CAD was 42%. Thomas et al., studied 60 patients less than 35 years of age following a first MI [48]. Significant CAD was present in 73.3%. However triple-vessel CAD was seen only in 5%. In 25% there was involvement of more or equal to three coronary artery segments. Although the rate of atherosclerotic involvement of any given vessel was less in patients 35 years old and younger, the rate of total occlusion is relatively high, implying acute thrombosis of a single-vessel lesion as a cause of infarction in patients with single-vessel disease and otherwise normal coronary arteries [12]. By comparison, prospective and retrospective analyses [12,47,49– 53] of patients b 35 years old have described angiographically normal coronary arteries in 9% to 17%. In our study 7.39% patients had normal coronary artery. The cause of the acute obstruction in patients without significant obstruction is still not completely clear; coronary spasm or thrombosis with reperfusion have been suggested as possible causes. Although the coronary angiogram does not demonstrate significant obstruction in these patients, this does not always exclude atherosclerosis with positive remodeling of the artery. Rupture of an insignificant plaque causing temporary obstruction by a clot may cause an infarct. Subsequent lysis is possible and may leave the lumen intact. Intravascular ultrasound of the coronary arteries, which provides a tomographic view of the arterial wall (not only the lumen), may reveal coronary artery disease despite an apparent normal coronary angiogram [27]. However, this is not undertaken routinely in our laboratory.
4.1. Study limitations This study did not have any control group and so the risk of each factor could not be analyzed. Also, the statistical significance of the factors couldn't be analyzed.
5. Conclusion Smoking was the most common risk factor of MI followed by dyslipidemia in very young adults. The mean time of presentation after the onset of the symptoms was 12.25 h. Acute anterior STEMI owing to occluded left anterior descending artery was more frequent. A majority of the patients had single vessel disease which was seen on coronary angiography. The cessation of smoking would play a major role in preventing MI in very young adults. Also, on the early hospitalization of these patients, they need to be educated on this topic.
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AMI in very young (aged ≤ 35 years) Bangladeshi patients: Risk factors & coronary angiographic profile Fazila-Tun-Nesa Malik ⁎, Md. Kalimuddin, Nazir Ahmed, Mohammad Badiuzzzaman, Mir Nesaruddin Ahmed, Ashok Dutta, Dhiman Banik, Md. Kabiruzzaman, Habibur Rahman, Tawfiq Shahriar Huq, Md. Farhad Jamal National Heart Foundation Hospital & Research Institute, Dhaka, Bangladesh
a r t i c l e
i n f o
Article history: Received 19 October 2015 Accepted 8 November 2015 Available online 11 November 2015 Keywords: Acute myocardial infarction Very young adults Risk factor Angiographic profile
a b s t r a c t Background: Coronary artery disease is a devastating disease precisely because an otherwise healthy person in the prime of life may die or become disabled without warning. When the afflicted individual is under the age of 35, the tragic consequences for family, friends, and occupation are particularly catastrophic and unexpected. The purpose of the present study was to assess the risk factors, angiographic profile, and in-hospital outcome of very young patients (aged ≤35 years) with first acute myocardial infarction (AMI). Methods: A cross-sectional study was conducted involving 266 young (≤35 years) patients with clinical diagnosis of AMI. They were studied for risk factors, clinical characteristics, and in-hospital outcome between February 2012 and October 2014 at the NHFH&RI, Dhaka, Bangladesh. Coronary angiography was done in 230 patients. Results: The mean age of patients was 31.19 ± 3.81 years; 94.7% were male. The major risk factor was smoking, followed by dyslipidemia, family history of ischemic heart disease. The most common anatomical location for the MI was the anterior wall. Significant coronary artery disease was found in 83.04% patients, 7.39% patients had normal coronaries. Most patients had single vessel disease followed by double-vessel disease. Left anterior descending was the commonest vessel involved followed by left circumflex artery. In-hospital mortality was 2.3%. Conclusion: AMI in very young almost exclusively occurs in male and smoking was the most common risk factor. Acute anterior MI owing to occluded left anterior descending artery was more frequent. Very young patients with an AMI have a favorable in-hospital mortality. © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Prior to World War II coronary artery disease in men under 30 years of age was regarded as rare, and in men between 30 and 40 years of age, as uncommon [1]. However, acute myocardial infarction (AMI) has been recognized in the young age groups more frequently in recent years [2]. Additionally, AMI in very young patients aged ≤35 years has been poorly described. It is estimated that less than 2% of all AMIs are patients aged ≤35 years [3]. The prevalence of CAD as well as AMI has progressively increased in Bangladesh during the beginning of the century, particularly among the very young urban population. The conventional risk factors do not fully explain the vulnerability of Bangladeshi community to coronary atherosclerosis. Hypertriglyceridemia, low levels of HDL-C, central obesity, high lipoprotein-a (Lp-a), high LDL-C, rising affluence, dietary habits, and rapid modernization associated with sedentary but stressful lifestyle in summation are suggested as additional risk factors for CAD. Apart from smoking, in addition, a subset of ST-segment elevation ⁎ Corresponding author. E-mail address: [email protected] (F.-T.-N. Malik).
myocardial infarction in the very young (≤35 years) is likely related to illicit drug use [4,5] or to nontraditional risk factors, such as oral contraceptive use [6]. Very young patients with ST-segment elevation myocardial infarction are likely to attribute chest pain to other causes and present late. In addition, physicians taking care of such patients also are less likely to consider cardiac cause for such pain in the very young, resulting in withholding of care, inadequate care, or delays in care. The pattern of care and outcomes of the very young with ST-segment elevation myocardial infarction is therefore not well defined [7]. Coronary angiography (CAG) performed in young patients with acute myocardial infarction has identified a relatively high incidence of normal coronary arteries, non-obstructive stenosis or single-vessel disease [8–10]. Very young patients seem to have lower morbidity, with the same mortality [11]. There is a dearth of available data concerning the risk factors, clinical features, coronary angiographic findings, natural history, and prognosis on very young adults with ST-segment elevation myocardial infarction (STEMI), as a life-threatening cardiac emergency condition. No study has been conducted in Bangladesh regarding angiographic characteristics of very young patients with STEMI. So, this study was conducted
http://dx.doi.org/10.1016/j.ctrsc.2015.11.003 2405-5875/© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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to learn the profile of very young patients (≤35 years) with acute myocardial infarction with an emphasis on: assessment of the risk factors; mode of presentation; coronary angiographic characterization and inhospital outcome. 2. Method The approval of the ethics committee of National Heart Foundation Hospital & Research Institute (NHFH & RI) was obtained. This study was conducted at NHFH & RI, Dhaka, Bangladesh from February 2012 to October 2014. All patients aged ≤35 years with first STEMI were included in the study. Patients with previous myocardial infarction, history of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) were excluded from the study. This was a cross-sectional study (case series) which enrolled 266 consecutive patients who fell into the inclusion criteria during this index period. We defined very young age as ≤35 years, definition that is similar to those used by others [1,5,7,11–18]. The risk factors which were studied were hypertension, diabetes mellitus, smoking habits, obesity (a BMI of N25 kg/m2), dyslipidemia, and a family history of ischemic heart disease. Current smokers were defined as individuals who smoked cigarettes in the previous 12 months. Individuals who had quit smoking more than a year earlier were classified as former smokers [19]. Participants were classified as physically active if they reported moderate (walking, cycling) or strenuous exercise (jogging, football, vigorous swimming) for 4 or more hours per week [19]. Coronary angiography was performed in 230 patients out of 266 to assess the number and type of vessels which were involved and percentage of lesion. Significant coronary disease was defined as at least a 70% reduction in the internal diameter of the right, left anterior descending or left circumflex coronary arteries and their branches, or ≥50% reduction in the internal diameter of the left main coronary artery. Moderate disease was defined as 50% to 69% stenosis of major coronary artery segments, 70% to 100% of minor segments or 30% to 49% of the left main coronary. Minimal disease was defined as less coronary obstruction than that for moderate disease. Angiographically normal coronaries had no appreciable stenoses. In the present analysis, patients with minimal or moderate disease were combined and classified as having nonobstructive disease [13]. 2.1. Statistical analysis The collected data were checked and coded manually and then entered into a computer database. The numerical data obtained from the study were analyzed. Data were expressed in frequency, percentage, mean and standard deviation as applicable. Data were analyzed by using computer based SPSS program version 16 for statistical analysis.
Table 1 Baseline characteristics of the patients (n = 266). Variables
Number (%)
Age (years) Sex (M/F) Urban Traditional risk factors: Smoking Hypertension Diabetes Dyslipidemia Family H/O IHD Obesity Other risk factors: Hyper-homocysteinemia(n = 106) Physical inactivity Substance abuse — amphetamine Substance abuse — cannabis Excessive fatty food consumption Energy drink abuse Inadequate vegetable intake
31.19 ± 3.81 252/14(94.7/5.3) 185(69.5) 206(77.4) 57(21.4) 45(16.9) 187(70.3) 126(47.4) 89(33.5) 62(58.5) 147(55.3) 14(5.3) 10(3.8) 127(47.7) 76(27.1) 103(38.7)
measured in 106 patients. Hyper-homocysteinemia was present in 62 (58.5%) patients. Physical inactivity was present in 55.3% patients and obesity in 33.5% patients. 47.7% patients had history of increased fatty food consumption. Substance abuse is very rare: Amphetamine — 5.3%; cannabis — 3.8% and energy drink 27.1%. Oral contraceptive drugs were used by 8 women (57.14%) out of 14. Two female were unmarried. The most common symptom was chest pain, which was present in 95.5% of the patients with radiation of pain (59.8%), followed by sweating (87.6%), nausea/vomiting 36.5% breathlessness (6.4%), and palpitations (3.8%). Twelve patients (4.5%) had atypical symptoms. Two patients complained only of severe weakness and 10 patients had pain either in left hand or in both hands. In our 266 patients, 88 (33.1%) experienced chest pains prior to their MI. Fifty two patients reported nonspecific chest pain and only 36(13.53%) gave a typical history of angina pectoris. The mean time of presentation after the onset of the symptoms was 12.25 ± 1.26 h. Anterior wall MI was found in 56.5% of the patients; 41.6% of them had inferior wall MI; 1.5% lateral wall MI and 0.4% (1) anterior & inferior. AMI was common among B, O, A and AB blood groups, respectively. Angiographic procedures were carried out in 230 patients (86.46%). The remaining 30 patients refused the procedure and 6 patients died before the angiographic study. The left anterior descending artery was infarct related artery (IRA) in 53.91% patients, right coronary artery in 11.31% and the left circumflex coronary artery in 27.39% patients, which was seen on coronary angiography (Table 3). A majority of the patients (68.27%) had single vessel disease which was seen on coronary angiography, followed by double vessel disease (18.69%). 7.39% had normal coronaries, 5.65% had multi vessel disease and 1.73% had left main disease. 7.39% patients had normal coronaries,
3. Results The mean age of the patients were 31.19 ± 3.81 years, with a maximum number of patients (62.8%) being within the age of 31–35 years and 3% of the patients being in the age group of ≤20 years. The frequency of AMI increased with age. The youngest patient was age 17.5 years old and the oldest was 35 years old. 94.7% of the patients were males. Baseline and clinical characteristics of patients are shown in Tables 1 & 2. Most of the patients were service holder (48.9%) followed by businessman (33.8%). AMI in very young patients was highly prevalent in urban population (69.5%). Smoking was most common risk factor for myocardial infarction (77.4%) in the young adults, hyperlipidemia being the second common risk factor (70.3%). 47.4% of the patients had a family history of ischemic heart disease (IHD). The incidence of hypertension (21.4%) and diabetes (16.9%) was very low among the patients. Homocysteine level was
Table 2 Clinical characteristics of the patients (n = 266). Variables Clinical presentation: Chest pain Shortness of breath Nausea/Vomiting Sweating Palpitation Atypical presentation Site of AMI: Anterior Inferior Lateral Anterior & inferior
Number (%) 254 (95.5) 17 (6.4) 97 (36.5) 233 (87.6) 10 (3.8) 12 (4.5) 150 (56.5) 111 (41.6) 4 (1.5) 1 (0.4)
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83.04% patients had significant CAD and 9.57% patients had nonobstructive disease. Of the 266 very young patients with AMI, 123 (46.24%) received intravenous lytic therapy (streptokinase). Primary PCI was performed in fifteen (5.6%) patients, lytic therapy & PCI in 40 (15%), and coronary angioplasty in fifty one (19.2%). There were no deaths during interventional procedures. The remaining patients were treated medically. In addition, we evaluated the in-hospital outcome of these patients, which included symptom-free discharge from hospital, post MI angina, heart failure, post MI arrhythmia, mitral regurgitation, cardiogenic shock cardiac arrest survivors and in-hospital mortality (Table 4). Seventy seven (28.9%) patients developed complications during the acute MI phase. Four (1.6%) of them had persistent chest pain, 27 (10.2%) developed heart failure. Heart failure was classified into four categories according to Killip classification. Killip II was found in 10(3.8%) patients, Killip III was found in 9 (3.4%) patients and Killip IV was found in 8 (3.0%) patients. Thirteen (5.2%) patients had severe rhythm disturbances — atrial fibrillation (1.2%), ventricular tachycardia (3.6%) or ventricular fibrillation 0.4%). Twelve (4.5%) patients had cardiogenic shock. Regarding AV block, I° AV Block was found in 2(0.8%) patients; II° AV Block was found in 3 (1.2%) patients and complete heart block (CHB) was found in 3 (1.2%) patients. Mitral regurgitation (MR) was found echocardiographically in 43 (16.2%) patients. Thirty seven (13.9%) patients developed mild MR and 6(2.4%) patients moderate MR. Three (1.2%) patients were survivors of cardiac arrest. Inhospital mortality occurred in 6 (2.4%). All six patients had extensive anterior AMI and cardiogenic shock. Five of them developed acute left ventricular failure. Three of these six patients had ventricular tachycardia and one complete heart block. Two of them had persistent chest pain. Three patients were thrombolysed with streptokinase. All patients had moderate left ventricular systolic dysfunction (five had EF ≤ 35% and one had 42%). 4. Discussion Coronary atherosclerosis begins early in life, but acute STEMI in adults aged ≤35 years are exceptional. In the past, various mechanisms have been studied; such as rupture of a vulnerable plaque or erosion of the endothelial layer, hypercoagulable states, coronary artery spasm, and inflammation, with atherosclerosis remaining the major cause [3]. Atherosclerotic course begins at birth and considerable lesions in coronary arteries may be apparent as early as the age of 25 or 30 years [20, 21]. The reasons for such brisk progression of atherosclerosis, leading to MI at an early age are still being investigated. Autopsy studies in youth showed a strong relationship involving the degree of atherosclerosis in the coronary arteries with LDL-cholesterol levels, smoking status, blood pressure, and body mass index, and this association was more striking when there was a clustering of the above mentioned risk factors [22]. The distribution of the ages of our patients showed a striking increase of the disease with ageing, which was a very obvious fact and was seen in earlier studies also [23,24].
Table 3 Coronary angiographic characteristics of the patients (n = 230). Variables Infarct related artery: Normal LAD LCX RCA Number of involved vessel: Normal SVD DVD TVD Left main disease
Number (%) 17 (7.39) 124 (53.91) 63 (27.39) 26 (11.31) 17 (7.39) 157 (68.27) 43 (18.69) 13 (5.65) 4 (1.73)
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Table 4 In-hospital outcome of the patients (n = 266). Variables
Number (%)
Persistent chest pain Heart failure AV block Arrhythmia Mitral regurgitation Cardiogenic shock Survivor of cardiac arrest Death
4 (1.6) 27 (10.2) 8 (3.2) 13 (5.2) 43 (16.2) 12 (4.8) 3 (1.2) 6 (2.4)
One of the best documented and the most consistent risk factors for coronary atherosclerosis seems to be the male sex. The protective effects of estrogens in preventing atherosclerosis have been clearly demonstrated in epidemiologic studies [25]. In one study [9], a profile of acute MI in young patients showed a male: female ratio of 20:1, which consistent with our study (19:1); other studies showed reduced ratio (10.1:1) [11]; 7.7:1 [12]; 5:1 [15]; 12.5:1 [16] and 9:1 [23], but the trend remains the same. Among the many factors that have been shown to be important are cigarette smoking, hyperlipidemia, family history of IHD, hypertension, the male sex and diabetes mellitus. These have generally been associated with an increased incidence of fibrous plaques and their sequelae. The associations are relatively strong and they are made on a group comparison basis, although all the studies have demonstrated a high degree of variability among individuals within even the most homogenous of groups [26]. Cigarette smoking is a well-known risk factor for the development of coronary artery disease in young patients. Numerous studies have highlighted elevated rates of tobacco use among very young patients who present with AMI, with percentages ranging from 62 to 90% [11– 13,15,17,27–29]. In agreement with previous reports, our study confirmed that cigarette smoking (77.4%) is one of the major risk factors. Smoking adversely affects all phases of atherosclerosis given that it hastens thrombotic process, instigates endothelial dysfunction, augments proinflammatory effects, and induces coronary vasoconstriction even in patients with normal coronary vasculature [29]. The results of the Lipid Research Clinics Trail [30,31] demonstrated a direct association between the plasma lipoprotein profile, the cholesterol levels and the morbidity and mortality from coronary atherosclerosis. Hyperlipidemia, which is very common in young Asian adults as per earlier studies [6,30–36], was the second common risk factor in our study. Diabetes and hypertension were less common in very young adults in our study, which was seen in earlier studies also [11–13,15,17,27– 29]. In our study 47.4% of patients had a positive family history of IHD which consistent with other studies [12–13,28,36]. In contrast to our study, some other studies showed low incidence of positive family history of IHD [11,15,17,27,29]. Obesity was the infrequent cause in all the earlier studies 3.3–20% [12, 17,29] but in our study it was 33.5%. In the present study, the hyperhomocysteinemia rate in patients with AMI was 58.5%, which was consistent with study done by Masoomi et al. [37], 49.4%. These observations are important for primary prevention of AMI in Bangladesh. The mechanisms that may explain how homocysteine can increase the risk of AMI include its effect on the vascular endothelium, platelets and its role in increasing the risk of thrombosis [38,39]. Physical inactivity was present in 53.5% patients. Chest pain was the most common presentation in our study, which was similar to earlier studies also [23,27,28,40]. The arrival of the patients at the health care facility was mostly delayed by N10 h, as seen in earlier studies also [41–43]. We too had a mean arrival time of 12.25 h. Alizadeasl et al. [44] in their study of ABO blood groups relation and AMI indicated that the incidence of ischemic heart disease was higher in subjects of blood group A or its subgroups. AMI was higher
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among A, then it was common among O, B and AB blood groups, respectively (A N O N B N AB) [11]. In contrast to these two studies the incidence of ischemic heart disease was higher in subjects of blood group B in our study. As in earlier studies [15,17,23,29], in our study too, anterior wall MI was very common among the patients aged ≤ 35 years. In contrast to our study, other authors [11,27] showed inferior wall MI (52% vs 45% and 40% vs 33.3%) as common location. Not much literature is available with respect to angiographic features in very young patients undergoing CAG, and when available they represent only a very small percentage of total population of young patients with CAD. Regarding the extent of coronary lesions, our cases showed a less evolved disease. As described in the literature, young adults are characterized by a less extensive coronary disease, mainly as one-vessel form. The less extensive coronary artery disease and high prevalence of complex lesions observed in young patients might suggest that premature coronary artery disease is associated with rapid disease progression rather than with a gradually evolving process [45]. We could see that single vessel disease was evidently more common among the young adults, which had been reported by others also earlier [13,15–17,23,28,29,46]. Gotsman et al., showed 53% patients had normal coronary arteries [27], which could be due to the small sample size, leading to an overestimation. In the study by Alizadehasl et al., forty three percent patients had normal coronary arteries [11], followed by SVD (30.1%). Wolfe et al. [12] from the USA analyzed angiographic features in 35 patients who were b35 years of age (1.5% of the total number catheterized). They were compared with 100 patients ≥ 55 years of age. They found a very low prevalence of triple-vessel CAD in the first group (14.3%) as compared to 43% in the second group. In the study by Glover et al. [47], 120 consecutive patients 35 years or younger underwent coronary angiography following a clinical MI. Significant CAD was seen in 78% and the prevalence of triple-vessel CAD was 42%. Thomas et al., studied 60 patients less than 35 years of age following a first MI [48]. Significant CAD was present in 73.3%. However triple-vessel CAD was seen only in 5%. In 25% there was involvement of more or equal to three coronary artery segments. Although the rate of atherosclerotic involvement of any given vessel was less in patients 35 years old and younger, the rate of total occlusion is relatively high, implying acute thrombosis of a single-vessel lesion as a cause of infarction in patients with single-vessel disease and otherwise normal coronary arteries [12]. By comparison, prospective and retrospective analyses [12,47,49– 53] of patients b 35 years old have described angiographically normal coronary arteries in 9% to 17%. In our study 7.39% patients had normal coronary artery. The cause of the acute obstruction in patients without significant obstruction is still not completely clear; coronary spasm or thrombosis with reperfusion have been suggested as possible causes. Although the coronary angiogram does not demonstrate significant obstruction in these patients, this does not always exclude atherosclerosis with positive remodeling of the artery. Rupture of an insignificant plaque causing temporary obstruction by a clot may cause an infarct. Subsequent lysis is possible and may leave the lumen intact. Intravascular ultrasound of the coronary arteries, which provides a tomographic view of the arterial wall (not only the lumen), may reveal coronary artery disease despite an apparent normal coronary angiogram [27]. However, this is not undertaken routinely in our laboratory.
4.1. Study limitations This study did not have any control group and so the risk of each factor could not be analyzed. Also, the statistical significance of the factors couldn't be analyzed.
5. Conclusion Smoking was the most common risk factor of MI followed by dyslipidemia in very young adults. The mean time of presentation after the onset of the symptoms was 12.25 h. Acute anterior STEMI owing to occluded left anterior descending artery was more frequent. A majority of the patients had single vessel disease which was seen on coronary angiography. The cessation of smoking would play a major role in preventing MI in very young adults. Also, on the early hospitalization of these patients, they need to be educated on this topic.
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