© Borgis - New Medicine 2/2004, s. 48-51
Zygmunt Chodorowski1, Jacek Sein Anand1, Jerzy Foerster2, Marcin Gruchała3, Krzysztof Chlebus3
Differences in lipid profile in patients with first myocardial infarction occurring at different ages
1 First Clinic of Internal Diseases and Acute Poisoning, Institute of Internal Medicine, Gdańsk Medical University, Gdańsk, Poland
2 Voivodeship Outpatient Gerontology Clinic, Gdańsk, Poland
3 First Clinic of Cardiac Diseases, Institute of Internal Medicine, Gdańsk Medical University, Gdańsk, Poland
Summary
Aim. Disorders of lipid metabolism occupy a prominent place among the numerous well-known risk factors for ischemic heart disease. Relatively little attention has been paid, however, to the behavior of the basic lipid metabolism parameters in particular age groups of patients with ischemic heart disease. The goal of our study was to trace the mutual relations between disorders of lipid metabolism and the patient´s age at the time of first myocardial infarction.
Method. Plasma lipid levels were examined in 1567 patients with first acute myocardial infarction, 944 men and 623 women, ranging in age from 26 to 100 years (mean 63.1±11.9). Six lipid parameters were analyzed: Total cholesterol (Tch), LDL-cholesterol (LDLch), HDL-cholesterol (HDLch), triglycerides (TG), atherogenic index (Tch/HDLch) and Gubner´s index (Tch/HDLch × TG). The patients were divided into four age groups: <40 years, 40-59 years, 60-79 years, and 80.
Results. Of the 6 lipid metabolism parameters, 4 (Tch, TG, atherogenic index, Gubner´s index) demonstrated a significant downward trend in the whole study population from 52 to 85 years, while LDL cholesterol declined only until age 68. Among men, all of the lipid indicators except for HDLch decreased significantly from 51 to 85 years. Among women, the downward tendency was similar; however, LDL-cholesterol values did not decline significantly.
Conclusion. Among all studied indicators of lipid metabolism, only HDL-cholesterol levels remained stable and did not change significantly with age in any of the study groups.
INTRODUCTION
Among the numerous risk factors known to be of etiopathogenic significance for ischemic heart disease, a particularly prominent place is occupied by disorders of lipid metabolism. This topic has been the subject of considerable research (1-10). Somewhat less interest has been shown, however, in the behavior of the basic parameters of lipid metabolism in various age groups among patients with ischemic heart disease (5, 10, 11, 15). The purpose of the present study, then, was to trace the mutual relations between disorders of lipid metabolism and the age of patients experiencing a first-time myocardial infarction (MI).
MATERIAL AND METHOD
Lipidograms were performed on 1567 patients with a first-time recent MI, including 944 men and 623 women ranging in age from 26 to 100 years (mean 63.1±11.9). The women in this study population were significantly older than the men (66.0±12.0 vs 61.2±11.5, p <0.001). All these patients were hospitalized at the First Clinic of Heart Diseases or the First Clinic of Internal Diseases at the Gdańsk Medical University from 1994 to 2002.
The study population was divided into four age groups:
– Group 1: <40 years, mean age 36.1±3.3;
– Group 2: 40-59 years, mean age 51.7±5.3;
– Group 3: 60-79 years, mean age 68.3±5.3;
– Group 4: 80 years, mean age 85.1±3.9.
The diagnosis of MI was made on the basis of the clinical picture, the classic ECG criteria, and elevated serum levels of troponine, creatine kinase, CK-MB cardiac fraction, and the aminotransferases AspAT and AlAT. The diagnosis of MI without Q fraction was based on the finding of increased serum activity of creatine kinase and its isoenzyme MB, and/or a concentration of troponine exceeding two times the upper limit of the norm. Only those patients were included in the study in whom blood was drawn for a lipid profile within the first 24 hours of an acute MI episode and centrifuged within 2 hours of collection (1). If necessary, the plasma was preserved at a temperature of –20°C until the chemical analyses were performed. The lipids – total cholesterol (Tch), triglycerides (TG), and the HDL fraction of total cholesterol (HDLch) – were assayed in serum by the generally accepted methods routinely used in the Department of Clinical Biochemistry at the Gdańsk Medical University. The LDL fraction of total cholesterol was established indirectly by using Friedewald´s equation (12):
LDL ch = Tch – HDLch – TG/5
This equation was used to calculate the concentration of LDLch only when the plasma level of TG did not exceed 400 mg/dl.
In addition to Tch, HDLch, LDLch, and TG, we calculated the atherogenic index:
Tch
HDLch
and the Gubner index:
Tch
HDLch
The exclusion criteria included the following:
– cirrhosis of the liver or other liver diseases with features of active hepatocyte damage;
– nephrotic syndrome;
– chronic kidney failure;
– hypothyroidism;
– use by the patients of thiazide diuretics, non-selective-blockers, estrogens and progestagens, anticonceptive drugs, statins, fibrates, nicotinic acid, anion-exchange resins, phenytoines, benzodiazepines, prebucol, or anabolic and parasympatholytic compounds;
– coronary angioplasty performed in the acute phase of MI (14).
For purposes of statistical analysis we used the test of significance for two factors of structure and the U-Mann-Whitney test.
RESULTS
The data concerning the number, gender, and age of the patients in the whole study population and the respective age groups are given in Tables 1, 2, and 3. As previously noted, the women in the study population were significantly older than the men; this was also true within groups 2 and 3 (Table 1). Tables 1-3 also show that there were more men than women: 60.2% vs. 39.8%, for a male-female ratio of ca. 1.5:1. The numerically smallest group consisted of patients under 40 years of age (n=42, constituting 2.5% of the study population), while the largest group was made up of patients in the age bracket 60-79 years (n=873 persons, 55.7% of the study population).
Table 1. Distribution of total cholesterol (Tch), LDL-cholesterol (LDLch), HDL-cholesterol (HDLch), triglycerides (TG), atherogenic index (Tch/HDLch) and Gubner index (Tch/HDLch × TG) in patients with first acute myocardial infarction in different age groups.
Parameters | Group 1 | Group 2 | Group 3 | Group 4 | p |
1 vs 2 | 2 vs 4 |
No. of patients | 42 | 536 | 873 | 116 | - | - |
Age brackets (year) | < 40 | 40-59 | 60-79 | 80 | - | - |
Age | 36.23.31 | 51.85.34 | 68.45.50 | 85.23.85 | - | - |
Tch (mg/dl) | 231.943.07 | 235.452.70 | 225.653.73 | 220.687.25 | 0.67 | < 0.02 |
LDLch (mg/dl) | 163.042.89 | 164.648.25 | 156.347.13 | 156.084.22 | 0.82 | < 0.01* |
HDLch (mg/dl) | 38.412.52 | 38.513.59 | 39.312.46 | 40.913.22 | 0.95 | 0.08 |
TG (mg/dl) | 152.871.90 | 169.097.16 | 153.7104.80 | 129.280.32 | 0.29 | < 0.001 |
Atherogenic index | 6.62.47 | 6.62.34 | 6.22.33 | 5.93.22 | 0.93 | < 0.01 |
Gubner index | 1124.3860.56 | 1212.61179.51 | 1043.51359.15 | 826.6901.59 | 0.63 | < 0.001 |
*gr. 2 vs gr. 3
Table 2. Distribution of total cholesterol (Tch), LDL-cholesterol (LDLch), HDL-cholesterol (HDLch), triglycerides (TG), atherogenic index (Tch/HDLch) and Gubner index (Tch/HDLch × TG) in men with first acute myocardial infarction in different age groups
Parameters | Group 1 | Group 2 | Group 3 | Group 4 | p |
1 vs 2 | 2 vs 4 |
No. of men | 33 | 351 | 518 | 42 | - | - |
Age brackets (year) | < 40 | 40-59 | 60-79 | 80 | - | - |
Age | 35.83.45 | 51.45.49 | 67.45.29 | 85.24.47 | - | - |
Tch (mg/dl) | 234.946.88 | 236.052.84 | 219.252.64 | 206.550.13 | 0.76 | < 0.001 |
LDLch (mg/dl) | 165.946.76 | 163.949.64 | 151.348.98 | 143.748.23 | 0.94 | < 0.01 |
HDLch (mg/dl) | 37.012.58 | 37.513.98 | 37.111.20 | 36.99.11 | 0.65 | 0.75 |
TG (mg/dl) | 160.275.29 | 173.0104.50 | 153.7124.75 | 129.597.86 | 0.71 | < 0.001 |
Atherogenic index | 7.02.60 | 6.82.44 | 6.32.30 | 6.02.36 | 0.84 | < 0.01 |
Gubner index | 1233.3916.16 | 1269.91275.35 | 1089.61674.27 | 898.71234.41 | 0.96 | < 0.001 |
Table 3. Distribution of total cholesterol (Tch), LDL-cholesterol (LDLch), HDL-cholesterol (HDLch), triglycerides (TG), atherogenic index (Tch/HDLch) and Gubner´s index (Tch/HDLch × TG) in women with first acute myocardial infarction in different age groups.
Parameters | Group 1 | Group 2 | Group 3 | Group 4 | p |
1 vs 2 | 2 vs 4 |
No. of women | 9 | 185 | 355 | 74 | - | - |
Age brackets (year) | < 40 | 40-59 | 60-79 | 80 | - | - |
Age | 37.32.54 | 52.55.00 | 69.85.51 | 85.13.47 | - | - |
Tch (mg/dl) | 220.823.23 | 234.352.56 | 235.053.99 | 228.7102.18 | 0.34 | < 0.05 |
LDLch (mg/dl) | 152.1222.72 | 161.747.23 | 161.748.08 | 143.798.83 | 0.56 | 0.08 |
HDLch (mg/dl) | 43.411.51 | 40.312.64 | 42.413.52 | 43.114.64 | 0.26 | 0.09 |
TG (mg/dl) | 125.952.75 | 161.481.18 | 153.565.97 | 129.169.16 | 0.17 | < 0.001 |
Atherogenic index | 5.41.43 | 6.22.08 | 6.02.37 | 5.93.64 | 0.18 | < 0.001 |
Gubner index | 724.4457.22 | 1103.8965.96 | 976.6673.08 | 785.1643.69 | 0.18 | < 0.001 |
Among all the lipid metabolism parameters shown in Tables 1-3 there were no statistically significant differences for groups 1 and 2, despite a certain rising tendency.
It can be inferred from the data included in Table 1 that in the entire study population the values of total cholesterol, triglycerides, the atherogenic index, and the Gubner index showed a statistically significant decline from Group 2 to Group 4. LDL-cholesterol, on the other hand, was significantly lower only between Group 2 and Group 3. HDL-cholesterol was the only parameter that did not change significantly in relation to the age of the MI patients.
The results shown in Table 2 indicate that five of the six lipid parameters – Tch, LDLch, TG, atherogenic index, Gubner index – were significantly lower among the men when Group 2 was compared to Group 4. Only HDL-cholesterol failed to show a significant dependence on age.
In the women (Table 3), the distribution of results in respect to four lipid parameters was similar to that of the entire study population: the plasma concentrations of Tch and TG, the atherogenic index, and the Gubner index showed a significant declining trend from Group 2 to Group 4, while the levels of LDL- and HDL-cholesterol did not vary significantly with age.
DISCUSSION
The research projects thus far conducted in respect to the basic lipid metabolism parameters have varied rather markedly in terms of the selection of groups, both regarding the average age and the cross-section of patients. In additional to persons who were clinically healthy, research has been focused on patients with ischemic heart disease in various stages of advancement; in only a few reports has part of the cohort consisted of persons with MI (1, 5, 8, 9, 11, 15). The basic components of the lipid profile have been investigated, generally speaking, in various and heterogeneous age groups, which markedly hinders the comparison of the results reported in these publications (1, 7, 10, 11, 15). The material described in the present study, by contrast, consists of a rather homogenous population of 1,567 patients hospitalized for a first MI. Due to the statistically significant age differences between the men and the women, however, both in the entire study population and in groups 2 and 3, it was not possible to compare the lipid metabolism parameters between the two genders. Accordingly, we analyzed only the distribution of the basic lipid parameters in four age brackets.
The data we obtained indicate clearly that, both in the entire study population and in the sub-population of men, four parameters – total cholesterol, triglycerides, atherogenic index and Gubner index – showed a statistically significant decline from age 52 to age 85. LDL-cholesterol continued to drop only to age 68 in the men, while in the women the decline was not statistically significant. The HDL-cholesterol fraction, on the other hand, maintained a relatively stable value with only slight, non-significant variations. Similar results, with a very slight upward trend in HDL-cholesterol, were obtained by Wallace and Colsher (10).
The results reported in most publications indicate that, along with advancing age, there is a drop in the plasma concentration of total cholesterol, triglycerides, and LDL cholesterol (5, 10, 11, 15). Discrepancies have involved only the age at which this drop begins. The prevailing opinion is that total cholesterol begins to drop between the ages of 50 and 65 (4, 11, 15). Ettinger et al., however, found a drop in total cholesterol, triglycerides, and LDL-cholesterol only after age 65 (5).
The reasons why lipid parameters decline with age have not been fully explained. It is generally assumed that, as a result of natural selection, persons with an unfavorable lipidogram die sooner, while those with a good lipidogram live longer. This way of explaining the mechanisms underlying the statistical changes in the lipid profile obtained in both our study and in other publications, is contradicted to a certain extent by the nearly constant level of HDL-cholesterol, which according to the "survival of the fittest” hypothesis should begin to rise significantly in older age groups (5, 10, 11, 15). An alternative hypothesis for explaining the observed phenomena assumes that the synthesis of some lipid factors, especially total cholesterol and triglycerides, declines in the elderly.
CONCLUSION
1. The mean values for total cholesterol and triglycerides, as well as the atherogenic index and the Gubner index, fell significantly from age 52 to 85, in the entire study population of first-time MI patients, whereas the level of LDL-cholesterol fell only to age 68.
2. Among the men in our study population, all the lipid metabolism parameters except for HDL-cholesterol showed a significant decline between age 51 and 85.
3. While displaying identical trends in respect to the other lipid parameters, the women differed in showing a nonsigificant decline in LDL-cholesterol.
4. Only the value of HDL-cholesterol was stable and did not change significantly with the progress of age in any of the cohorts we examined.
Piśmiennictwo
1. Akosah K.O., Corniglia R.M., Harlik P., Schaper A.: Myocardial infarction in young adults with low-density lipoprotein cholesterol levels < or = 100 mg/dL: clinical profile and 1-year outcomes. Chest. 2001; 120:1953-8. 2.Anderson K.M., Wilson W.F., Odell P.M., Kannel W.B.: An updated coronary risk profile: A statement for health professionals. Circulation. 1991; 8:356-62. 3.Benfante R., Reed D.: Is elevated serum cholesterol level a risk factor for coronary heart disease in the elderly? JAMA 1990; 263:393-6. 4.Castelli W.P., Anderson K., Wilson P.W., Levy D.: Lipids and risk of coronary heart disease: the Framingham Study. Ann. Epidemiol. 1992; 2:23-8. 5.Ettinger W.H., Wahl P.W., Kuller L.H. et al.: Lipoprotein lipid in older people: Results from the Cardiovascular Health Study. Circulation. 1992; 86:858-69. 6.Gotto A.M.: Prognostic and therapeutic significance of low levels of high-density lipoprotein cholesterol: Current perspectives. Arch. Intern. Med. 1999; 159:1038-40. 7.Jacobsen S.J., Freedman D.S., Hoffman R.G. et al.: Cholesterol and coronary artery disease: age as an effect modifier. J. Clin. Epidemiol. 1992; 10:1053-9. 8.Lamarche B., Despres J.P., Moorjani S. et al.: Prevalence of dyslipidemic phenotypes in ischaemic heart disease: Prospective results from the Quebec Cardiovascular Study. Am. J. Cardiol. 1995; 75:1189-95. 9. Rubins H.B., Schectman G., Wilt T.J. et al.: Distribution of lipid phenotypes in community-living men with coronary heart disease. Arch. Intern. Med. 1992; 152:2412-6. 10.Wallace R.B., Colsher P.L.: Blood lipid distributions in older persons: Prevalence and correlates of hyperlipidiemia. Ann. Epidemiol. 1992; 2:15-21. 11.Vincelj J., Sucic M., Bergovec M. et al.: Serum total, LDL, HDL cholesterol and triglycerides related to age, gender and cigarette smoking in patients with first acute myocardial infarction. Coll. Antropol. 1997; 21:517-24. 12. Friedewald W.T., Levy R., Fredrickson D.: Estimation of the concentration of low-density-lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin. Chem. 1972; 18:499-502. 13. Gubner R.S.: A grading index of serum lipid abnormalities. Am. J. Cardiol. 1992; 70:1514-14. 14.Miida T., Otsuka H., Tsuchiya A., Okada M.: Plasma lipoprotein profiles change significantly during cardiac catheterization. Clin. Chem. 1998; 44:517-21. 15.Kreisberg R.A., Kasim S.: Cholesterol metabolism and aging. Am. J. Med. 1987; 82:54-60.