|
It is still controversial whether or not the correlation between lipid abnormality and coronary heart disease (CHD) becomes weaker in the elderly, and whether patients above 80 years old still benefit from lipid management for the secondary prevention of CHD.［1］ Therefore, we carried out a long-term follow-up study on 1211 retirees to assess the relationship between hyperlipidemia and the risk of CHD, and to determine if it is appropriate to use lipid-lowering drugs in the elderly.
METHODS
This project was initiated in 1986, with the goal of carrying out a long-term follow-up study on the relationship between lipid abnormalities and cardiovascular disease in the elderly. Five hundred subjects were initially enrolled in 1986－1987, and a total of 1247 participated thereafter. Personal life habits and medical history were recorded. All subjects received a physical examination and blood chemistry survey every year. Information on incidental illnesses was also recorded. From 1986 until the year 2000, 1211 subjects were studied, including those who died during the follow-up period. The drop out rate was 3%. The average follow-up period was 11.2±3.7 years, of which 54% patients were followed up for 10 years or more, and 35% for 15 years or more. Among the 1211 cases, 1109 were male and 102 were female. Female cases were not grouped separately due to the small number. The average initial age was 70±9 years, and the average age in the end of the study or at the time of death was 80±9 years (including 8 centenarians, aged 100-102).
Most of the subjects were retired government officers with good living conditions and medical care. Their daily dietary intake was stable, unaffected by the gradual changes in the market supply of commodities over the past 20 years (although no detailed nutritional survey was performed). Their personal life habits, including smoking, alcohol drinking, and exercise, as well as body mass index (BMI), are summarized in Table 1 .
The end points of this study were either attacks of acute myocardial infarction (AMI) or death due to CHD or any other causes. Many of the suspected CHD cases were not included in this study, because their conditions were not confirmed by coronary angiography. A total of 397 subjects died within 15 years, with cancer the primary cause of death, and CHD (89 cases) the secondary cause of death. Sixty-three subjects with CHD died of AMI (29 subjects had repeated attacks of AMI), 12 subjects died of coronary sudden death, and others of heart failure, ventricular fibrillation, AMI with ruptured ventricular aneurysms, etc. A total of 214 subjects, including patients who died of CHD and AMI survivors (125 cases), were assigned to the CHD group. Diagnosis of AMI was based on the 1979 WHO standard. Autopsy results were reviewed (autopsy rate was 61%).
Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG, measured as total glycerol) levels were analyzed according to the requirements of serum lipid standardization.［2］ Classification of lipid and lipoprotein levels was in accordance with “Recommended Guidelines for Management of Dyslipidemia”, formulated by cardiovascular specialists in China,［2］ TC≥5.17 mmol/L （200 mg/dl） and TG≥1.69 mmol/L （150 mg/dl） were defined as high serum lipid level. Low HDL-C was designated as <1.03 mmol/L （40 mg/dl）. Due to large biological variations between individuals,［3］ lipid levels for each individual were determined by the trend of all the measurements. Most subjects did not receive statin or fibrate treatment, and various nonspecific lipid-modulating agents did not affect their lipid levels. Statistical results from the first and the last 3 years of the follow-up period showed that the lipid levels did not change significantly although their ages increased by more than 10 years.
The elderly individuals participating in this study suffered from a variety of chronic diseases. Three hundred and thirty-eight subjects in relatively good health (with no apparent cerebral or cardiovascular disease, hypertension, diabetes mellitus, endocrinopathy, or liver or renal diseases) were classified as the healthy group, and their lipid levels were designated as baseline. For the study of the relationship between lipid abnormality and CHD or death from other causes, the mortality rate was compared between the high and normal lipid groups. For multivariate analysis of CHD risk factors, those cases without a history of cerebro-vascular accidents were grouped as a control in comparison with the CHD group. Both univariate analysis and multivariate analysis were performed using SAS software, version 6.12. A P value less than 0.05 was considered significant.
RESULTS
Statistical analysis of CHD risk factors
Univariate analysis ( Table 1 ) shows that age, hypertension, diabetes, LDL-C, and HDL-C are risk factors for CHD, among which LDL-C and HDL-C are the most significant lipid risk factors. However, there were no significant differences in TG, sex, BMI, and other lifestyle habits between the two groups. Smoking history was complicated by the fact that some smokers gave up smoking and some smoked intermittently. Results show that the difference in percentage of smokers is not significant between the CHD and control groups. Acute coronary events increase significantly with aging (P=0.001) from 50 to 79 years of age, but the relationship between AMI incidence and age is not significant after 80 years of age (P=0.3002).
Multivariate analysis (logistic regression, Table 2 ) also shows that, age, hypertension, LDL-C, and HDL-C are important risk factors for CHD, and that other parameters are not risk factors. Diabetes was nearly a significant risk factor according to logistic regression (P=0.0571), although it was found to be a very significant risk factor using univariate analysis.
Relationship between lipid levels and death due to CHD or any other cause
Many of the subjects in our study were at an advanced age, and faced a high mortality rate. Three hundred and ninety-seven (32.8%) subjects died during the 15-year follow-up study. All the subjects were divided into 2 groups according to TC and TG levels. The total death rate in the high lipid group (31.5%) was lower than that in the normal (and low) lipid group (35.3%), though the difference was not statistically significant. CHD (mostly AMI) death was higher in the high lipid group. By contrast, deaths due to cancer, pneumonia, and other diseases were more likely in the normal lipid group. The cumulative number of coronary deaths was 89 (88 cases above the age of 70) ( Table 3 ).
Characteristic lipid patterns in the experimental subjects
The average lipid levels of the healthy group (338 cases) were: TC 5.24 mmol/L (202 mg/dl), LDL-C 3.13 mmol/L (121 mg/dl), HDL-C 1.29 mmol/L (50 mg/dl), TG 1.68 mmol/L (149 mg/dl; medium value: 137 mg/dl). Compared with all subjects, only HDL-C was slightly higher. TC, LDL-C, and TG levels were similar in both groups, but the CHD group had higher TC and LDL-C levels.
In the healthy group, 35.2% had normal TC and TG, 38.8% and 15.8% had high (including borderline high) TC and TG, respectively. 12.1% had combined hyperlipidemia. Therefore, high TC is more prevalent than high TG (an observation also true of the CHD group). Low HDL-C occurred in 16.9% of the healthy group, while high HDL-C occurred in 12.4% of this group. When looking at all subjects (1211 cases), 2/3 of patients suffered from hyperlipidemia, with a ratio of high TC to high TG of about 2∶1. 23.2% had low HDL-C, while 8.3% had high HDL-C. 51.6% had TC≥5.17 mmol/L (200 mg/dl), 31.5% had TC≥5.69 mmol/L (220 mg/dl), and 12.1% had TC≥6.21 mmol/L (240 mg/dl). TC levels were higher than those previously reported by our group.［4］
Among our subjects, HDL-C was higher in women than in men (1.44 vs 1.23 mmol/L, P<0.0001). TC and LDL-C were also higher in women, but there was no difference in TG levels (medium value: male, 1.58 mmol/L; female, 1.51 mmol/L, P=0.8990). It is commonly believed that lipid levels decrease after age 60. However, our data demonstrates that TC (and LDL-C) reach a peak value in the 65-74 age group, and remain stable around 5.17 mmol/L in the 60-100 year old age group. HDL-C levels were relatively stable in every age group, but TG decreased significantly after age 70.
Treatment of hyperlipidemia
Health care doctors are usually cautious in the treatment of hyperlipidemia in the elderly. There is concern over the balance between side effects and benefits and there is uncertainty over whether or not elderly patients can endure long-term lipid-lowering therapy. In our study, patients themselves paid much attention to their own lifestyle adjustments, including giving up smoking, practicing temperance in eating and drinking, and increasing physical exercise. Only 45% received lipid-lowering agents, most of them with Chinese traditional medicine or polyunsaturated fatty acids. Few subjects took statin or fibrates intermittently (124 and 153 cases, respectively).
DISCUSSION
In brief, we have demonstrated that: ① Hyperlipidemia occurs in 2/3 of elderly people, with the most common lipid disorder being borderline high TC (and LDL-C) levels. Only 12% of elderly individuals have a TC level≥6.21 mmol/L (240 mg/dl). ② TC (LDL-C) levels do not necessarily decrease with aging.［1］ Mean TC (and LDL-C) reach peak levels at age 65-74 (older than previously reported), and remain around 5.17 mmol/L (200 mg/dl) even after the age of 90. This last result is in agreement with our previous report. By contrast, TG levels decrease after age 70. ③ High TC is much more prevalent than high TG. ④ 23% of our subjects had HDL-C levels <1.03 mmol/L (40 mg/dl), and 8% had HDL-C levels >1.55 mmol/L (60 mg/dl). Low HDL-C can be found in individuals with normal TC and TG levels. However, among those with high TG (>1.7 mmol/L), more than 50% of these cases have low HDL-C.
Few prospective studies have examined the relationship between dyslipidemia and CHD in individuals above the age of 75. In our study, 72.6% of the 1211 subjects were over 75 years old by the end of the follow-up study. The cumulative total death rate during the 15-year follow-up period was lower in the high lipid group than in the normal lipid group. This result might become statistically significant if the total number of cases were increased. Similar studies have reported that the total mortality rate among the elderly is higher in low TC individuals than in high TC individuals, probably due to a higher death rate as a result of cancer or infections in the former group.［5,6］
However, in our study, the CHD death rate was significantly higher in the hyperlipidemia group than in the normal lipid group. If AMI survivors are included in the results, the number of CHD cases is even higher in the hyperlipidemia group. Taken together, these results suggest that hyperlipidemia is still an important risk factor for CHD in the advanced elderly. It is commonly believed that high TC and LDL-C are not as useful in determining the risk of CHD in the elderly as in middle-aged subjects. Our data demonstrates that TC and LDL-C levels were still higher in the CHD group than in the controls, although the difference in levels between these two groups was less than 0.25 mmol/L (10 mg/dl). The cumulative death rate of CHD among our subjects was much higher than that reported elsewhere in China (in younger subjects), but still much lower than that reported in other countries.［7］
There is great controversy over whether or not elderly patients with lipid abnormalities (mainly high TC and LDL-C) should receive the same treatments as younger patients. Recent studies have shown that high TC and LDL-C are still risk factors for CHD in the elderly,［8］ but these studies did not focus on subjects above 75 years in age. Among the subjects of this study, high TC (LDL-C) and AMI were prevalent (the cumulative 15 year rate of AMI attacks was about 10% in the age groups of 80-89 and 90-102). Therefore, much attention should be given to the advanced elderly suffering from dyslipidemia. Although no studies have been carried out examining the secondary prevention of CHD in individuals over 75 years old, with improvements in living conditions and the prolongation of life expectancy, the average time spent as an elderly individual has been extended (by as much as 40 years). Consequently, more clinical and subclinical CHD cases may be encountered. Lipid lowering therapy might be given to those elderly CHD patients in generally good health but with higher TC (LDL-C) levels. The first choice of treatment should be the changing of living habits and intervention in the multiple CHD risk factors that commonly aggregate in the elderly. Drug therapy may be beneficial for older patients with CHD or diabetes. Doctors tend to be cautious about whether the elderly can tolerate and adhere to long-term drug therapy. Few side effects have been observed in the most commonly used lipid-lowering drugs. Treatments should follow the “Recommended Guidelines for Management of Dyslipidemia” formulated by Chinese specialists and the U.S. Adult Treatment Panel Ⅲ (ATP-Ⅲ) Guidelines.［9］ The LDL-C target for CHD and diabetes patients is 2.6 mmol/L（100 mg/dl）, and further lowering is not necessary. It remains to be determined if elderly patients should use a less strict therapy protocol. In addition, attention should also be paid to low TC levels, as they may indicate the presence of subclinical diseases,［10］ and may also increase total death rate.
Acknowledgment: We thank Dr. Qian Yi-jian, Honorary President of Beijing Hospital, for reading this manuscript and providing helpful comments.
REFERENCES
1.Li JZ. Serum lipids (In: Geriatrics progress of China in recent 50 years). Chin J Geriatr Med (Chin) 1989;18:265-267.
2.Dislipidemia treatment panel. Recommended guidelines for prevention and treatment of dislipidemia. Chin J Cardiovasc Dis (Chin) 1997;25:169-175.
3.Li JZ, Chen WX, Wang S, et al. Long-term biological variability of serum lipids. Chin J Lab Med (Chin) 2002; 30:647-650.
4.Li JZ, Niu QT, Wang S, et al. Variation of serum lipids, lipoproteins and apolipoproteins in the elderly. Chin J Geriatr Med (Chin) 1990;9:200-205.
5.Weverling-Rijnsburger AWE, Blauw GJ, Lagaay AM, et al. Total cholesterol and risk of mortality in the oldest old. Lancet 1997;350:1119-1123.
6.Shatz IJ, Masaki K, Yano K, et al. Cholesterol and all cause mortality in elderly people from the Honolulu heart program: a cohort study. Lancet 2001;358:351-355.
7.Pearson TA, Criqui MH, Luepha RV, et al. Primer in preventive cardiology, Dallas： AHA; 1994:5.
8.Grundy SM, Cleeman JI, Rifkind BM, et al. Cholesterol lowering in the elderly population. Arch Intern Med 1999;159:1670-1678.
9.Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel Ⅲ). JAMA 2001;285:2486-2497.
10.Shepherd J. Issues surrounding age: vascular disease in the elderly. Curr Opin Lipidology 2001;12:601-609.
|
PDF(-)
Rapid Response |