Lipid Profiles of Acute Coronary Syndrome Patients Hospitalized in ICCU of Cipto Mangunkusumo Hospital

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1 ORIGINAL ARTICLE Lipid Profiles of Acute Coronary Syndrome Patients Hospitalized in ICCU of Cipto Mangunkusumo Hospital Daulat Manurung ABSTRACT Aim: to see which component of the triad lipid that has more important role and frequently found in patients with acute coronary syndrome, focusing on HDL cholesterol. Methods: a lipid profile study has been conducted in 391 patients with acute coronary syndrome (ACS), who have been hospitalized in ICCU of Cipto Mangunkusumo Hospital since January 1 st, 2001 December 31 st, Results: there were 294 male patients (75.2%) and 97 female patients (24.8%), from years age group, with mean value ± The mean value of total cholesterol level was mg/dl ± The LDL cholesterol level was mg/dl ± The mean HDL cholesterol level was mg/dl ± 10.28, mean triglycerides level was mg/dl ± There were 82 patients (21%) with high total cholesterol (> 240 mg/dl), 102 patients (26.1%) with high and very high LDL cholesterol level (> 160 mg/dl), 152 (38.6%) patients with low HDL cholesterol level (< 40 mg/dl), consisted of 126 male patients or 42.9% of total male patients, 26 female patients or 26.8% of total female patients. The number of patients with high / very high triglycerides level (> 200 mg/dl or 500 mg/dl) was 84 patients (21.5%). The number of patients with optimal lipid level, total cholesterol level < 200 mg/dl was 191 patients (48.8%); 82 patients (21%) had LDL cholesterol level < 100 mg/dl, 23 patients (5.9%) had HDL cholesterol level > 60 mg/dl, 226 patients (57.8%) had triglycerides level < 150 mg/dl. There were 260 patients with atherogenic lipid profile (64%), 135 patients with borderline lipid profile (34.5%), and optimal lipid profile was found only in 6 patients (1,5%). The mean value of HDL cholesterol level in male patients was mg/dl ± 9.9, while HDL cholesterol level in female patients was mg/dl ± Principally, lipid profiles of all age groups were evenly distributed. ACS patients with history of family heart disease had a more atherogenic lipid profile compared to lipid profile of patients with hypertension, diabetes mellitus, and cigarette smoking. Division of Cardiology, Department of Internal Medicine Faculty of Medicine, University of Indonesia-dr. Cipto Mangunkusumo Hospital, Jakarta Conclusion: atherogenic lipid profile is more common risk factor in ACS patients than in other non-lipid risk factors. This study also demonstrated that the atherogenic lipid is most commonly found in patient with low HDL cholesterol level and it is least frequently found in patient with optimal lipid profile. Key words : lipid profile, acute coronary syndrome. INTRODUCTION Elevated blood cholesterol level is a main risk factor of atherosclerosis process, which underlies the development of coronary heart disease, including acute coronary syndrome. Total blood cholesterol consists of Low Density Lipoprotein (LDL) cholesterol, which is the largest component of total cholesterol, i.e % of total cholesterol. 1 LDL cholesterol is very atherogenic (a very atherogenic lipoprotein) and it should be decreased and represents the major cause of CHD, it should be decreased. The correlation between elevated LDL cholesterol level and CHD development should be observed as a multi step process, which starts from the young age. 2,3,4 Plaque rupture or erosion usually leads to acute coronary syndrome (acute myocardial infarct, unstable angina pectoris and sudden death caused by coronary heart disease). 5-8 The second cholesterol component is high density lipoprotein (HDL) cholesterol. Normally, it is 20-30% of total cholesterol. HDL cholesterol is one of important lipoproteins and is very potential to prevent atherosclerosis by changing the biology of arterial wall lesion, without being affected by LDL cholesterol level. 9 HDL cholesterol has two mechanisms causing changes in biology of arterial wall lesion. Correlation between blood triglyceride level and CHD may be derived from various mechanisms such as, triglycerides may which cause a more atherogenic LDL cholesterol. It may cause higher clearance rate of HDL cholesterol, which finally causes low HDL cholesterol level. may cause endothelial dysfunction, 196

2 Vol 38 4 October - December 2006 Lipid Profiles of Acute Coronary Syndrome Patients Hospitalized and may stimulate macrophages migration into endothelium. It may also stimulate vascular endothelial to promote thrombogenic mediator synthesis, for example: Plasminogen Activator Inhibitor (PAI-1). 10 NCEP /ATP III regards < 150mg/dL as optimal level mg/dl as borderline level, mg/dl as high level, and > 500 mg/dl as very high level. 1 In this study, we will see, which component of the triad lipid that has more important role and frequently found in patients with acute coronary syndrome, focusing on HDL cholesterol. METHODS This study was a retrospective cross-sectional study based on medical records of ACS patients in Cipto Mangunkusumo Hospital ICCU from January 1 st, 2001 to December 31 st, RESULTS During the course of study (January 1 st, 2001) December 31 st, 2005), there were 568 patients with acute coronary syndrome (ACS) hospitalized in ICCU (Intensive Coronary Care Unit) of Cipto Mangunkusumo Hospital. There were 391 patients, i.e. 294 male (75.2%) and 97 female (24.8%), who had complete lipid profile records including total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. The study also recorded the non-lipid coronary risk factors such as diabetes mellitus in 132 patients (33.8%), hypertension in 229 patients (58.6%), smoking in 205 patients (52.4%), familial heart disease in 61 patients (15.6 %). The subjects age was about years old with mean value of 57.35± The mean value of total cholesterol level was ± 54.84, LDL cholesterol level was ±47.29 mg/dl, HDL cholesterol level was ± mg/dl, and triglycerides level was ± mg/dl. (Table 1) Table 1. Mean Value of Lipid Profile in ACS Lipid Profile Total cholesterol mg/dl ± LDL cholesterol mg/dl ± HDL cholesterol mg/dl ± mg/dl ± There were 82 patients (21%) with high total cholesterol level (> 240 mg/dl), 191 patients (48.8%) with total cholesterol less than 200 mg/dl and 118 patients (30.2%) with borderline cholesterol level between mg/dl. (Table 2) Table 2. Distribution of Total esterol Level in ACS Total esterol of Patient > 240 high borderline < 200 desired There were 41 patients (10.5%) with LDL cholesterol level more than 190 mg/dl (very high level), 61 patients (15.6%) with LDL cholesterol level between mg/dl (high level), 101 patients (25.8%) with LDL cholesterol level between mg/dl, 106 patients (27.1%) with LDL cholesterol level between mg/dl, and 82 patients (21%) with LDL cholesterol level less than 100 mg/dl (optimal level). (Table 3) Table 3. Distribution of LDL esterol Level in ACS LDL esterol of Patient > 190 very high high nearly high beyond optimal < 100 optimal Patients with high HDL cholesterol level > 60 mg/dl were 23 patients (5.9%) of all ACS patients, consisting of 12 male patients (3.1%) and 11 female patients (11.3%). (Table 4) Table 4. Distribution of Level in ACS of Patient > 60 mg/dl high mg/dl borderline < 40 mg/ dl low There were 126 male patients (42.9 %) and 26 female patients (26.8%) among total number of 152 patients (38.6%) with low HDL cholesterol level, less than 40 mg/dl. (Table 5) While total HDL cholesterol level in male was mg/dl ± 9.9, and the level in female was mg/dl ±

3 Daulat Manurung Acta Med Indones-Indones J Intern Med Table 5. Distribution of Level < 40 mg/dl in ACS Sex of Patient Male (294 subjects) Female (97 subjects) Total (391 subjects) There were 84 patients (21.5%) with high triglyceride level > 200 mg/dl, 2 patients with very high triglyceride level > 500 mg/dl (0.5%). There were also 226 patients with triglyceride level of <150 mg/dl (57.8 %) and 81 patients with triglyceride level of mg/dl (20.7%). (Table 6) Table 6. Distribution of Triglyceride Level in ACS < > 500 of Patient Furthermore, there were 82 patients (21%) with high total cholesterol level more than 240 mg/dl, 102 patients (26.1%) with high LDL cholesterol level more than 160mg/dl. There were 152 patients (38.6%) with low HDL cholesterol level < 40 mg/dl and 84 patients (21.5%) with high triglyceride level > 200 mg/dl. (Table 7) Table 7. Distribution of Patients with Atherogenic Lipid in ACS Lipid Category Total esterol > 240 LDL esterol > 160 Low < 40 > In keeping with optimal lipid profile level, there were 191 patients (48.8%) with total cholesterol level < 200 mg/dl, 82 patients (21%) with LDL cholesterol level < 100 mg/dl. There were also 23 patients (5.9%) with high HDL cholesterol > 60 mg/dl and 226 patients (57.8%) with triglyceride level < 150 mg/dl. (Table 8). But according to the combination of atherogenic lipid triad (High LDL level, low HDL level, and high triglyceride level), there were 10 patients (2.6%) who had complete atherogenic lipid profile. Table 8. Distribution of Patients with Optimal Lipid Level in ACS Lipid Category Total esterol <200 LDL esterol < 100 > 60 < If it calculated based on two combination of atherogenic lipid, there were 68 patients (17.4 %), while if it calculated based on single atherogenic lipid, there were 172 patients (44%). No lipid atherogenic was found in 141 patients (36 %). Moreover, if the three lipid types were optimal, only six patients were found (1.5 %). There were 141 patients 6 patients 135 patients with borderline lipid profile (34.5 %). (Table 9) Table 9. Combination of Lipid Triad in ACS patients Lipid Combination N % 3 atherogenic lipid atherogenic lipid atherogenic lipid Borderline lipid Optimal lipid In keeping with percentage of two atherogenic lipid combination, there were 32 patients with combination of low HDL level and high triglyceride level (8.2 %). There were 21 patients with combination of high triglyceride level and high LDL level (5.4 %) and 15 patients with combination of low HDL level and high LDL level (3.8%). (Table 10) Table 10. Combination of Two Atherogenic Lipid in 391 ACS Patients Lipid Combination N % Low High High LDL esterol, High High LDL esterol, Low HDL esterol Total Lipid distribution based on Age Group may be seen on table 11. While lipid profile in patients with non-lipid risk factor of coronary heart disease, hypertension, smoking, diabetes mellitus and history of familial heart disease may be seen in table 12, 13, 14,

4 Vol 38 4 October - December 2006 Lipid Profiles of Acute Coronary Syndrome Patients Hospitalized Table 11. Distribution of Lipid Profile Based on Age Group Age. Group Num % Total LDL HDL Trig ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±62.70 >= ± ± ± ±60.13 Table 12. Lipid Profile in ACS Patients with Hypertension (N = 229; 58.8%) Total esterol LDL esterol ± ± ± ± Table 13. Lipid Profile in ACS Patients with Smoking Habit (N = 205; 52.4%) Total esterol LDL esterol HDL esterol ± ± ± ± Table 14. Lipid Profile in ACS Patients with Diabetes (N = 132; 33.7%) Total esterol LDL esterol ± ± ± ± Table 15. Lipid Profile in ACS Patients With History of Familial Heart Disease Total esterol LDL esterol ± ± ± ± DISCUSSION The lipid profile including total cholesterol level, LDL cholesterol level, HDL cholesterol level, and triglyceride level obtained from other studies in western countries/ from literature have similar results to this study. 11,12 A study of CHD population in Jakarta also has similar result. 13 (Table 16) There is a correlation between low HDL cholesterol level and other atherogenic factors. Most of individuals with low HDL cholesterol level demonstrate a correlation to high triglycerides and remnant lipoprotein levels (quoted of reference 1). In addition, low HDL cholesterol level usually correlated to small dense LDL particle. 27 There is strong correlation between low HDL cholesterol level, high LDL cholesterol level, and high triglycerides level, which demonstrate the term of Lipid Triad as mentioned before. In this study, we may observe that among atherogenic lipid, combinations, the combination of low HDL cholesterol level and low triglycerides is the most 199

5 Daulat Manurung Acta Med Indones-Indones J Intern Med Table 16. Comparison of Lipid Profile in Present Study and Other Studies (Nissen et al 11 ) (Nissen et al 12 ) (Sarwono 13 ) (Present Study) Total esterol 204 (41.2) 232 ± ± ± LDL esterol (34.3) 150 ± ± ± (11.1) 426 ± ± ± (81.7) ± ± ± common, including 32 patients (8.2%). While the combination of high LDL cholesterol level and high triglycerides level is on the second rank with 21 patients (5.4%) and the least frequent combination is high LDL cholesterol disorder and short of breath, which is found in 15 patients or 3.8%. (Table 10) It is also noted that among 391 ACS patients, there are 250 patients (64%) who have atherogenic lipid, and the most common is only in single atherogenic lipid found in 172 patients (44%). About 68 patients (17.4%) have combination of two atherogenic lipid, while optimal lipid profile is only found in 6 patients (1.5%) of 391 patients. In addition, lipid profile of borderline level is found in 135 patients (34.5%). (Table 9) Among four non-lipid coronary risk factors, lipid profile of ACS patients with familial history have a more atherogenic lipid profile, which indicates higher LDL cholesterol and triglycerides level compared to other patients with smoking habit, hypertension and diabetes mellitus. The most common non-lipid coronary risk factors are hypertension in 229 patients (58.8%), followed by smoking in 205 patients (52.4%), diabetes in 132 patients (33.7%), and the least common is history of familial heart disease in 61 patients (15.1%). In keeping with the distribution of atherogenic lipid profile, low HDL cholesterol level is the most common atherogenic lipid, which is found in 152 patients (38.6%), while high LDL cholesterol level, high triglycerides level and high total cholesterol level are relatively similar, which are 26.1%, 21.5% and 21 % respectively (Table 7). Furthermore, among 152 patients with low HDL cholesterol, there are 126 male patients (42.9%) and 26 female patients (26.8%). This result is lower than in Framingham study, which shows 57% male CHD patients with HDL cholesterol level < 40 mg/dl, while the CARE study indicates 40% female patients with acute infarct have HDL cholesterol level of < 40mg/dL. But from these data, it is clear that ACS patients with low HDL level are more found in male group (42.9%) than the female (26.8%). In contrast, high HDL cholesterol level is more frequently found in female group (11.3%) than male (3.1%) (table 4.5). The mean value of HDL cholesterol level is lower in male group (41.75mg/dl ±9.9) compared to female (46.16mg/dL ± 10.74). These data 13, are similar to data found from previous studies. In relation to optimal lipid profile, the most common is optimal triglycerides level < 150 mg/dl, which is found in 226 patients (57.8%), followed by total cholesterol level < 200 in 191 patients (48.8%) and the least frequent is HDL cholesterol, which is only found in 23 patients (5.9%). (Table 8) The most common lipid distribution is total cholesterol level of < 200 in 191 patients (48.8%). LDL cholesterol level between is found in 207 patients (52.9%), borderline HDL cholesterol level of mg/dl is found in 216 patients (55.5%), triglycerides level of < 150 is found in 226 patients (57.8%). (Table 2, 3, 4, 6) While the composition of lipid profile based on age group is evenly distributed, although the age group of years has higher triglycerides level compared to other age groups, and the age group > 80 years has higher total cholesterol and LDL level. Higher cholesterol level is found in the age group of > 70 years and > 80 years compared to other age groups. It is interesting that the younger age group has a lower HDL cholesterol level, lower total cholesterol level, lower LDL cholesterol level, and also lower triglycerides level (isolated low HDL cholesterol?) (quoted of reference 1), but it only occurs in 2 patients, therefore it is difficult to regard this as a comparison. (Table 11) CONCLUSION The composition of lipid profile in this study is relatively similar to other data in western countries. Among 391 ACS patients, it is found that the most common atherogenic lipid is low HDL cholesterol about 38.6%, while the number/percentage of other atherogenic lipid is relatively similar. There are 64% atherogenic lipid found as single atherogenic lipid, and there are only about 1.5% who have optimal lipid profile, and 34.5% who have borderline lipid profile. It also demonstrates that mean value of HDL cholesterol level is higher in female than in male group. Combination of low HDL cholesterol and 200

6 Vol 38 4 October - December 2006 Lipid Profiles of Acute Coronary Syndrome Patients Hospitalized high triglycerides level is about 8.2%, high LDL cholesterol and high triglycerides level are about 5.4% and combination of high LDL cholesterol level and low HDL cholesterol level is about 3.8%. The most common optimal lipid profile is triglycerides and total cholesterol level, i.e. 57.8% and 48.8% respectively. The most common non-lipid coronary risk factor is hypertension (58.8%) and smoking (52.4%). The more atherogenic lipid profile lipid is found in patients with history of familial heart disease. This study is a retrospective study, therefore it is not known whether the patient already had any previous therapy of hypolipidemic agents, and there is no record about it. This obviously affects the cholesterol examination of hospitalized ACS patients. Other risk factors, such as metabolic syndrome, are not recorded, but the major coronary risk factors have been included in this study. Since low HDL cholesterol is the largest component of other atherogenic lipids, education about increasing HDL cholesterol is important in order to provide primary prevention by emphasizing the importance of total health life changes ACKNOWLEDGEMENT I would like to thank dr. Taufik for his endeavor to collect the medical data in this study and to Ms. Sri Rahayu Kadarwati, SKM for her help in preparing this manuscript. REFERENCES 1. Third Report of the National Kolesterol Education Program (NCEP), Expert Panel On Detection, Evaluation, and Treatment of High Blood Kolesterol in Adults (Adult Treatment Panel III/ ATP III). (Final Report). National Institutes of Health. National Heart, Lung, And Blood Institute. NIH Publication No September Stary HC, Blankenhorn DH, et al. A definition of the intima of human arteries and of its atheroslerosis prone regions: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1992;85: Stary HC, ChandLer AB, et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb. 1994:14: Stary HC, ChandLer AB, et al. A definition of advanced types of atherosclerotic lesions and histological classification of atherosclerosis; a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995;92: Libby P. Molecular bases of the acute coronary syndromes. Circulation. 1995;91: Libby P, Schoenbeck U, et al. Current concepts in cardiovascular pathology: the role of LDL cholesterol in plaque rupture and stabilization. Am J Med. 1998;104(2A):14S-8S. 7. Fuster V, Fayad ZA, Badimon JJ. Acute coronary syndromes: biology. Lancet. 1999;353(suppl II):S115-S9. 8. Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non-q-wave myocardial infarction. Circulation. 1998;97: Castelli W. esterol and lipids in the risk of coronary artery disease. The Framingham Heart Study. Can J Cardiol. 1988;4(suppl A):5a-10a. 10. Hokanson J, Austin M. Plasma triglyceride and coronary risk.a metaanalysis. Circulation. 1993, 88: Nissen Steven E, Nicholls SJ, et al. Effect of very highintensity statin therapy on regression of coronary atherosclerosis. The ASTEROID Trial. JAMA. 2006;295: Nissen Steven E, Tuzcu E Murat, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med. 2005;352(1): Waspadji S. Lipid profile in urban population. Jakarta: a decade interval. Jakarta diabetes meeting Jakarta: Pusat Penerbitan Departemen Ilmu Penyakit Dalam FKUI; Austin MA, Rodriguez BL, et al. Low-density lipoprotein particle size, triglycerides, and high density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men. Am J Cardiol. 2000;86: Johnson CL, Rifkind BM, et al. Declining serum total cholesterol levels among US adults: the national health and nutrition examination surveys. JAMA. 1993;269: Kannel WB. Range of serum cholesterol in the population developing coronary artery disease. Am J Cardiol. 1995; 76(suppl):69C-77C. 17. Lewis SJ, Sacks FM, et al. Effect of pravastatin on cardiovascular events in women after myocardial infarction: the cholesterol and recurrent events trial. J Am Coll Cardiol. 1998;32:

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