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HDL cholesterol predicts coronary heart disease mortality in older persons
KNOWLEDGE
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Serum Lipids Four Weeks After Acute Myocardial Infarction Are a Valid Basis for Lipid Lowering Intervention in Patients Receiving Thrombolysis R. Carlsson,G. Lindberg,L Westin, B. Israelsson.Sectionof Cardiology,Department of Medicine,CentralHospital,I(arlstad,Sweden.Br HeartJ 1995;74:18-20. Objective: To compare serum concentrations of total choles-
(LDL) cholesterol concentrations improves coronary artery stenosis. Most patients in previous trials have had at least mildly elevated LDL. Recently, however, the Harvard Atherosclerosis Reversibility Project (HARP) did not find such benefit in patients with lower baseline LDL levels compared with previous trials. We reviewed and analyzed all cholesterol-lowering trials that used angiographic endpoints. Unifactorial trials of hypocholesterolemic dietary or drug therapy demonstrated that the higher the baseline LDL, the greater the improvement in quantitatively determined stenosis in the treatment group compared with the controls (r = .83). Considering the change in stenosis in the treatment group alone, regression was more common in trials in which baseline mean LDL was >170 mg/dl (>4.4 mmol/ liter), whereas progression occurred when baseline mean LDL was <170 mg/dl (<4.4 mmol/liter). HARP had the lowest baseline LDL (137 mg/dl [3.54 mmol/liter]), and showed no tendency for improvement in lesions. In contrast to the influence of baseline LDL levels, neither a low LDL level achieved on treatment nor a large percentage reduction in LDL was related to improvement in lesions. Sample size differences between HARP and the other trials are unlikely to be a major explanatory factor, since trials of comparable sample size to HARP, but with higher initial LDL, demonstrated favorable results. We conclude that coronary lesions that develop in the context of average LDL levels show less angiographic improvement in response to substantial LDL reduction than lesions in hypercholesterolemic patients. However, the clinical relevance of this finding awaits results from ongoing clinical endpoint trials in the normocholesterolemic population.
terol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides four weeks after acute myocardial infarction with baseline levels measured within 24 hours after onset of symptoms. Design: A prospective study including 141 patients with acute myocardial infarction who were admitted to the coronary care unit at a general hospital. Measurements: Fasting serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. Main results: In patients receiving thrombolytic therapy, no significant differences were found in serum lipids four weeks after admission compared to values estimated within 24 hours from onset of symptoms. In patients not receiving thrombolytic therapy, total cholesterol and low density lipoprotein cholesterol showed a minor increase four weeks after admission compared to values obtained within 24 hours after onset of symptoms. High density lipoprotein cholesterol and triglycerides remained unchanged. Conclusions: In patients with acute myocardial infarction receiving thrombolytic therapy, serum lipids measured four weeks after onset of infarction are reasonably valid estimates of baseline lipid levels and may be used to decide about lipid lowering interventions. This information can be a basis for actions against hyperlipidaemia early after hospital discharge when the patient is highly motivated to change lifestyles and is still in close contact with a cardiologist or other physician.
Baseline Serum Cholesterol and Treatment Effect in the Scandinavian Simvastatin Survival Study (4S) I.R. Pedersen,J. I(jehhus,K. Berg,I. Haghfelt,O. Faergeman,G. Thorgeirsson, IC Pyorala,T. Miettinen,L Wilhelmsen,A.G.Ol~on, E. Wedel.CardiologySection, MedicalDepartment,Aker Hospital,Oslo,Non~ay.Lancet1995;345:1274-5.
HDL Cholesterol Predicts Coronary Heart Disease Mortality in Older Persons M.-C. Corti,].M. Gu~lnik, M.E. Salive,T. Harris,T.S. Field,R.B.Wallace,LF. Berkman,T.E. Seeman,Iq. Glynn,C.H. Hennekens,~J. HavliL EDBP,National Instituteon Aging,NIH, Bethesda,MD. JAMA1995;274:539-44. Objectives: To examine the relationship of total cholesterol
We examined the relation between the risk of major coronary events (coronary death and non-fatal myocardial infarction) and baseline cholesterol levels in patients with coronary heart disease, randomised to placebo or simvastatin therapy in the Scandinavian Simvastatin Survival Study (4S). The relative risk reduction in the simvastatin group was 35% (95% CI 15-50) in the lowest quartile of baseline low-density lipoprotein cholesterol and 36% (19-49) in the highest. Simvastatin significantly reduced the risk of major coronary events in all quartiles of baseline total, high-density lipoprotein, and low-density lipoprotein cholesterol, by a similar amount in each quartile.
and high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) mortality and with occurrence of new CHD events in persons aged 71 years and older. Design: Prospective cohort study with a median of 4.4 years of follow-up. Setting: East Boston, Mass; New Haven, Conn; and Iowa and Washington counties, Iowa. Participants: A total of 2527 women and 1377 men who completed an interview, had serum lipid determinations, and survived at least 1 year. New CHD events were evaluated in persons with no CHD history or hospitalization. Main Outcome Measures: Death due to CHD (ICD-9 codes 410 through 414 as underlying cause of death); new occurrence of CHD events
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KNOWLEDGE
(fatal CHD or hospitalization with CHD [ICD-9 codes 410 through 414]). Results: After adjustment for established CHD risk factors, the relative risk (RR) of death due to CHD for those with low HDL-C (<0.90 mmol/L [<35 mg/dL]) compared with the reference group (HDL-C >- 1.55 mmol/L [>-60 mg/dL]) was 2.5 (95% confidence interval [CI], 1.6 to 4.0). Elevated risk was present in subgroups aged 71 through 80 years (RR, 4.1; 95% CI, 1.9 to 8.8) and over 80 years (RR, 1.8; 95% CI, 0.99 to 3.4), and in men and women. Low HDL-C predicted an increased risk of occurrence of new CHD events (RR, 1.4; 95% CI, 1.1 to 2.0), with similar but nonsignificant results in subgroups of men and women. Total cholesterol was less consistently associated with CHD mortality than HDL-C. When we compared individuals with total cholesterol of at least 6.20 mmol/L (240 mg/dL) with the reference group with total cholesterol of 4.16 to 5.19 mmol/L (161 to 199 mg/dL), a significant risk of CHD mortality was seen for women (RR, 1.8; 95% CI, 1.03 to 3.0) but not for men (RR, 1.0; 95% CI, 0.5 to 2.0). In the total population, for each 1-unit increase in the total cholesterol/HDL-C ratio there was a 17% increase in the risk of CHD death that was statistically significant. Conclusions: Low HDL-C predicts CHD mortality and occurrence of new CHD events in persons older than 70 years. Elevated total cholesterol was not found to be associated with CHD mortality in older men, but may be a risk factor for CHD in older women.
BASE
1.12 (95 percent confidence interval, 0.96 to 1.31), as compared with the men in the bottom fifth (median, 0.07 g per day). For men who consumed six or more servings of fish per week, as compared with those who consumed one serving per month or less, the multivariate relative risk of coronary disease was 1.14 (95 percent confidence interval, 0.86 to 1.51). The risk of death due to coronary disease among men who ate any amount of fish, as compared with those who ate no fish, was 0.74 (95 percent confidence interval, 0.44 to 1.23), but the risk did not decrease as fish consumption increased. Conclusions: Although the possibility of residual confounding by unmeasured factors cannot be entirely excluded, these data suggest that increasing fish intake from one to two servings per week to five to six servings per week does not substantially reduce the risk of coronary heart disease among men who are initially free of cardiovascular disease.
The Effect of Fasting Status on the Determination of Low-Density and High-Density Lipoprotein Cholesterol LB. Wilder, P.S. Bachofik,C~. Finney,T.F. Moy,D.M. Becker.J. HopkinsCenterfor Health Promotion,Baltimore,MD. Am J Med 1995;99:374-7. Purpose: To determine the effect of a self-selected meal on concentrations of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in a screening setting and to determine the effect of using nonfasting values to classify individuals according to National Cholesterol Education Program guidelines. Subjects and Methods: Study subjects were 115 employees who had previously participated in worksite total cholesterol screening, selected by stratified random sampling for sex and total cholesterol levels. Total cholesterol, triglycerides, HDL-C, and estimated LDL-C were determined before subjects ate a self-selected breakfast and 3 and 5 hours after eating it. Results: LDL-C values determined 3 and 5 hours following breakfast were approximately 7% and 2.5% lower, respectively, than fasting values. Use of 3-hour and 5-hour LDL-C determinations to classify individuals with elevated fasting levels (>-3.36 mmolFL) resulted in false-negative rates of 20% and 14%, respectively. Three- and 5-hour HDL-C values were approximately 4% and 1.5% lower, respectively, than fasting levels. Use of 3-hour HDL-C values to classify individuals with low fasting levels (<0.91 mmol/L) resulted in no false-negatives, whereas 1 of 7 individuals with low fasting HDL-C was misclassified when 5-hour values were used. Conclusions: These results support the 1993 National Cholesterol Education Program guidelines that LDL-C levels should be determined only in fasting persons, and that nonfasting HDL-C values may be acceptable for screening purposes.
Dietary Intake of Marine n-3 Fatty Acids, Fish Intake, and the Risk of Coronary Disease Among Men A. Aschefio,E.B. Rimm,M.J.Stampfer,E.L Giovannucci,W.C Willetc Departmentof Nutrition,HarvardSchoolof PublicHealth,Boston,M~ N EnglJ Med 1995;332: 977-82. Background: It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question. Methods: In 1986, 44,895 male health professionals, 40 to 75 years of age, who were free of known cardiovascular disease completed detailed and validated dietary questionnaires as part of the Health Professionals. Follow-up Study: During six years of follow-up, we documented 1543 coronary events in this group: 264 deaths from coronary disease, 547 nonfatal myocardial infarctions, and 732 coronary-artery bypass or angioplasty procedures. Results: After controlling for age and several coronary risk factors, we observed no significant associations between dietary intake of n-3 fatty acids or fish intake and the risk of coronary disease. For men in the top fifth of the group in terms of intake of n-3 fatty acids (median, 0.58 g per day), the multivariate relative risk of coronary heart disease was
ACC CURRENTJOURNAL REVIEW May/June 1996
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Serum Lipids Four Weeks After Acute Myocardial Infarction Are a Valid Basis for Lipid Lowering Intervention in Patients Receiving Thrombolysis R. Carlsson,G. Lindberg,L Westin, B. Israelsson.Sectionof Cardiology,Department of Medicine,CentralHospital,I(arlstad,Sweden.Br HeartJ 1995;74:18-20. Objective: To compare serum concentrations of total choles-
(LDL) cholesterol concentrations improves coronary artery stenosis. Most patients in previous trials have had at least mildly elevated LDL. Recently, however, the Harvard Atherosclerosis Reversibility Project (HARP) did not find such benefit in patients with lower baseline LDL levels compared with previous trials. We reviewed and analyzed all cholesterol-lowering trials that used angiographic endpoints. Unifactorial trials of hypocholesterolemic dietary or drug therapy demonstrated that the higher the baseline LDL, the greater the improvement in quantitatively determined stenosis in the treatment group compared with the controls (r = .83). Considering the change in stenosis in the treatment group alone, regression was more common in trials in which baseline mean LDL was >170 mg/dl (>4.4 mmol/ liter), whereas progression occurred when baseline mean LDL was <170 mg/dl (<4.4 mmol/liter). HARP had the lowest baseline LDL (137 mg/dl [3.54 mmol/liter]), and showed no tendency for improvement in lesions. In contrast to the influence of baseline LDL levels, neither a low LDL level achieved on treatment nor a large percentage reduction in LDL was related to improvement in lesions. Sample size differences between HARP and the other trials are unlikely to be a major explanatory factor, since trials of comparable sample size to HARP, but with higher initial LDL, demonstrated favorable results. We conclude that coronary lesions that develop in the context of average LDL levels show less angiographic improvement in response to substantial LDL reduction than lesions in hypercholesterolemic patients. However, the clinical relevance of this finding awaits results from ongoing clinical endpoint trials in the normocholesterolemic population.
terol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides four weeks after acute myocardial infarction with baseline levels measured within 24 hours after onset of symptoms. Design: A prospective study including 141 patients with acute myocardial infarction who were admitted to the coronary care unit at a general hospital. Measurements: Fasting serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. Main results: In patients receiving thrombolytic therapy, no significant differences were found in serum lipids four weeks after admission compared to values estimated within 24 hours from onset of symptoms. In patients not receiving thrombolytic therapy, total cholesterol and low density lipoprotein cholesterol showed a minor increase four weeks after admission compared to values obtained within 24 hours after onset of symptoms. High density lipoprotein cholesterol and triglycerides remained unchanged. Conclusions: In patients with acute myocardial infarction receiving thrombolytic therapy, serum lipids measured four weeks after onset of infarction are reasonably valid estimates of baseline lipid levels and may be used to decide about lipid lowering interventions. This information can be a basis for actions against hyperlipidaemia early after hospital discharge when the patient is highly motivated to change lifestyles and is still in close contact with a cardiologist or other physician.
Baseline Serum Cholesterol and Treatment Effect in the Scandinavian Simvastatin Survival Study (4S) I.R. Pedersen,J. I(jehhus,K. Berg,I. Haghfelt,O. Faergeman,G. Thorgeirsson, IC Pyorala,T. Miettinen,L Wilhelmsen,A.G.Ol~on, E. Wedel.CardiologySection, MedicalDepartment,Aker Hospital,Oslo,Non~ay.Lancet1995;345:1274-5.
HDL Cholesterol Predicts Coronary Heart Disease Mortality in Older Persons M.-C. Corti,].M. Gu~lnik, M.E. Salive,T. Harris,T.S. Field,R.B.Wallace,LF. Berkman,T.E. Seeman,Iq. Glynn,C.H. Hennekens,~J. HavliL EDBP,National Instituteon Aging,NIH, Bethesda,MD. JAMA1995;274:539-44. Objectives: To examine the relationship of total cholesterol
We examined the relation between the risk of major coronary events (coronary death and non-fatal myocardial infarction) and baseline cholesterol levels in patients with coronary heart disease, randomised to placebo or simvastatin therapy in the Scandinavian Simvastatin Survival Study (4S). The relative risk reduction in the simvastatin group was 35% (95% CI 15-50) in the lowest quartile of baseline low-density lipoprotein cholesterol and 36% (19-49) in the highest. Simvastatin significantly reduced the risk of major coronary events in all quartiles of baseline total, high-density lipoprotein, and low-density lipoprotein cholesterol, by a similar amount in each quartile.
and high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) mortality and with occurrence of new CHD events in persons aged 71 years and older. Design: Prospective cohort study with a median of 4.4 years of follow-up. Setting: East Boston, Mass; New Haven, Conn; and Iowa and Washington counties, Iowa. Participants: A total of 2527 women and 1377 men who completed an interview, had serum lipid determinations, and survived at least 1 year. New CHD events were evaluated in persons with no CHD history or hospitalization. Main Outcome Measures: Death due to CHD (ICD-9 codes 410 through 414 as underlying cause of death); new occurrence of CHD events
ACC CURRENTJOURNAL REVIEW May/June 1996
38
KNOWLEDGE
(fatal CHD or hospitalization with CHD [ICD-9 codes 410 through 414]). Results: After adjustment for established CHD risk factors, the relative risk (RR) of death due to CHD for those with low HDL-C (<0.90 mmol/L [<35 mg/dL]) compared with the reference group (HDL-C >- 1.55 mmol/L [>-60 mg/dL]) was 2.5 (95% confidence interval [CI], 1.6 to 4.0). Elevated risk was present in subgroups aged 71 through 80 years (RR, 4.1; 95% CI, 1.9 to 8.8) and over 80 years (RR, 1.8; 95% CI, 0.99 to 3.4), and in men and women. Low HDL-C predicted an increased risk of occurrence of new CHD events (RR, 1.4; 95% CI, 1.1 to 2.0), with similar but nonsignificant results in subgroups of men and women. Total cholesterol was less consistently associated with CHD mortality than HDL-C. When we compared individuals with total cholesterol of at least 6.20 mmol/L (240 mg/dL) with the reference group with total cholesterol of 4.16 to 5.19 mmol/L (161 to 199 mg/dL), a significant risk of CHD mortality was seen for women (RR, 1.8; 95% CI, 1.03 to 3.0) but not for men (RR, 1.0; 95% CI, 0.5 to 2.0). In the total population, for each 1-unit increase in the total cholesterol/HDL-C ratio there was a 17% increase in the risk of CHD death that was statistically significant. Conclusions: Low HDL-C predicts CHD mortality and occurrence of new CHD events in persons older than 70 years. Elevated total cholesterol was not found to be associated with CHD mortality in older men, but may be a risk factor for CHD in older women.
BASE
1.12 (95 percent confidence interval, 0.96 to 1.31), as compared with the men in the bottom fifth (median, 0.07 g per day). For men who consumed six or more servings of fish per week, as compared with those who consumed one serving per month or less, the multivariate relative risk of coronary disease was 1.14 (95 percent confidence interval, 0.86 to 1.51). The risk of death due to coronary disease among men who ate any amount of fish, as compared with those who ate no fish, was 0.74 (95 percent confidence interval, 0.44 to 1.23), but the risk did not decrease as fish consumption increased. Conclusions: Although the possibility of residual confounding by unmeasured factors cannot be entirely excluded, these data suggest that increasing fish intake from one to two servings per week to five to six servings per week does not substantially reduce the risk of coronary heart disease among men who are initially free of cardiovascular disease.
The Effect of Fasting Status on the Determination of Low-Density and High-Density Lipoprotein Cholesterol LB. Wilder, P.S. Bachofik,C~. Finney,T.F. Moy,D.M. Becker.J. HopkinsCenterfor Health Promotion,Baltimore,MD. Am J Med 1995;99:374-7. Purpose: To determine the effect of a self-selected meal on concentrations of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in a screening setting and to determine the effect of using nonfasting values to classify individuals according to National Cholesterol Education Program guidelines. Subjects and Methods: Study subjects were 115 employees who had previously participated in worksite total cholesterol screening, selected by stratified random sampling for sex and total cholesterol levels. Total cholesterol, triglycerides, HDL-C, and estimated LDL-C were determined before subjects ate a self-selected breakfast and 3 and 5 hours after eating it. Results: LDL-C values determined 3 and 5 hours following breakfast were approximately 7% and 2.5% lower, respectively, than fasting values. Use of 3-hour and 5-hour LDL-C determinations to classify individuals with elevated fasting levels (>-3.36 mmolFL) resulted in false-negative rates of 20% and 14%, respectively. Three- and 5-hour HDL-C values were approximately 4% and 1.5% lower, respectively, than fasting levels. Use of 3-hour HDL-C values to classify individuals with low fasting levels (<0.91 mmol/L) resulted in no false-negatives, whereas 1 of 7 individuals with low fasting HDL-C was misclassified when 5-hour values were used. Conclusions: These results support the 1993 National Cholesterol Education Program guidelines that LDL-C levels should be determined only in fasting persons, and that nonfasting HDL-C values may be acceptable for screening purposes.
Dietary Intake of Marine n-3 Fatty Acids, Fish Intake, and the Risk of Coronary Disease Among Men A. Aschefio,E.B. Rimm,M.J.Stampfer,E.L Giovannucci,W.C Willetc Departmentof Nutrition,HarvardSchoolof PublicHealth,Boston,M~ N EnglJ Med 1995;332: 977-82. Background: It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question. Methods: In 1986, 44,895 male health professionals, 40 to 75 years of age, who were free of known cardiovascular disease completed detailed and validated dietary questionnaires as part of the Health Professionals. Follow-up Study: During six years of follow-up, we documented 1543 coronary events in this group: 264 deaths from coronary disease, 547 nonfatal myocardial infarctions, and 732 coronary-artery bypass or angioplasty procedures. Results: After controlling for age and several coronary risk factors, we observed no significant associations between dietary intake of n-3 fatty acids or fish intake and the risk of coronary disease. For men in the top fifth of the group in terms of intake of n-3 fatty acids (median, 0.58 g per day), the multivariate relative risk of coronary heart disease was
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