Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57:M333-M335 (2002)
© 2002 The Gerontological Society of America

Incidence of New Atherothrombotic Brain Infarction in Older Persons With Prior Myocardial Infarction and Serum Low-Density Lipoprotein Cholesterol >=125 mg/dl Treated With Statins Versus No Lipid-Lowering Drug

Wilbert S. Aronowa, Chul Ahnb and Hal Gutsteinc

a Cardiology Division, Westchester Medical Center/New York Medical College, Valhalla
b The Division of Clinical Epidemiology, University of Texas Medical School at Houston
c Neurocare Associates, Bronx, New York

Wilbert S. Aronow, Cardiology Division, New York Medical College, 23 Pebble Way, New Rochelle, NY 10804 E-mail: WSAronow{at}aol.com.


   Abstract
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 Abstract
Methods
 Results
 Discussion
 References
 
Background. We report the incidence of new atherothrombotic brain infarction (ABI) in older men and women with prior myocardial infarction and a serum low-density lipoprotein (LDL) cholesterol of >=125 mg/dl treated with statins and with no lipid-lowering drug.

Methods. The incidence of new ABI was investigated in an observational prospective study of 1410 men and women, mean age 81 ± 9 years, with prior myocardial infarction and a serum LDL cholesterol of >=125 mg/dl treated with statins (679 persons or 48%) and with no lipid-lowering drug (731 persons or 52%). Follow-up was 36 ± 21 months.

Results. At follow-up, the stepwise Cox regression model showed that significant independent predictors of new ABI were age (risk ratio = 1.04 for a 1-year increase in age), cigarette smoking (risk ratio = 3.5), hypertension (risk ratio = 3.1), diabetes mellitus (risk ratio = 2.3), initial serum LDL cholesterol (risk ratio = 1.01 for each 1 mg/dl increase), initial serum high-density lipoprotein cholesterol (risk ratio = 0.97 for each 1 mg/dl increase), prior stroke (risk ratio = 2.5), and use of statins (risk ratio = 0.40). The Cochran-Armitage test showed a trend in the reduction of new ABI in persons treated with statins as the level of serum LDL cholesterol decreased ( p < .0001).

Conclusions. Use of statins caused a 60%, significant, independent reduction in new ABI in older men and women with prior myocardial infarction and a serum LDL cholesterol of >=125 mg/dl.

OLDER persons with coronary artery disease and hypercholesterolemia or elevated serum low-density lipoprotein (LDL) cholesterol treated with simvastatin or pravastatin had a significant reduction in new stroke (1)(2)(3). We are reporting data from an observational study investigating the effects of statins on the incidence of new atherothrombotic brain infarction (ABI) in older men and women with prior myocardial infarction and a serum LDL cholesterol >=125 mg/dl followed prospectively for the incidence of new ABI.


   Methods
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Results
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Nine hundred and twenty-two women and 488 men, mean age 81 ± 9 years (range 60 to 100), with prior myocardial infarction and a serum LDL cholesterol >=125 mg/dl treated with a statin or with no lipid-lowering drug were followed prospectively in a long-term health care facility for the incidence of new ABI. Persons were considered to have prior myocardial infarction if they had a documented clinical history of myocardial infarction or electrocardiographic evidence of Q-wave myocardial infarction (4). Prior ABI and new ABI were diagnosed by a neurologist as previously described (5). The focal neurological signs of ischemic stroke were explained by loss of function in a restricted area of the brain corresponding to a particular vascular territory (5). New ABI was also confirmed by computerized axial tomography in 285 of 291 persons (98%).

Systemic hypertension was diagnosed according to the criteria of the Sixth Joint National Committee Report on the Detection, Evaluation, and Treatment of Hypertension (6). All persons with hypertension were treated with antihypertensive therapy. Diabetes mellitus was diagnosed according to the American Diabetes Association's new criteria (7). Of the 529 persons with diabetes mellitus, 464 (88%) were treated with insulin or oral hypoglycemic drugs, and 65 persons (12%) were treated with diet alone. Fasting serum lipids were drawn in all persons after a 12- to 14-hour overnight fast at baseline, after 1 month of therapy, and every 6 months during the study. A serum LDL cholesterol of >=125 mg/dl was considered elevated. A serum high-density lipoprotein (HDL) cholesterol <=35 mg/dl was considered decreased. A serum triglycerides level >=190 mg/dl was considered increased. A person was considered obese if the body mass index exceeded 30 kg/m2.

In this study, the full-time staff physicians taking care of the persons treated 679 of 1410 persons (48%) with a statin and 731 persons (52%) with no lipid-lowering drug. Of the 679 persons treated with a statin, 603 (89%) were treated with simvastatin, 68 (10%) were treated with pravastatin, and eight (1%) were treated with lovastatin. The attitude of different physicians toward treating hypercholesterolemia in older persons with prior myocardial infarction determined whether or not statins were prescribed. Follow-up was 36 ± 21 months (range 1 to 133 months).

Chi-square tests were used to analyze dichotomous variables, and Student's t tests were used for continuous variables (Table 1 , Table 2 , and Table 4 ). Table 3 shows the prognostic variables for new ABI and their regression coefficients in the stepwise Cox regression model. The Cochran-Armitage test was used to examine if there was a trend in the reduction of new ABI in persons treated with statins as the last level of serum LDL cholesterol decreased (Table 5 ).


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  		Table 1. Baseline Characteristics of Persons With Prior Myocardial Infarction and Elevated Serum Low-Density Lipoprotein Cholesterol Treated With Statins Versus No Lipid-Lowering Drug

 

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  		Table 2. Incidence of New Atherothrombotic Brain Infarction in Persons With Prior Myocardial Infarction and Elevated Serum Low-Density Lipoprotein Cholesterol Treated With Statins Versus No Lipid-Lowering Drug

 

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  		Table 4. Incidence of New Atherothrombotic Brain Infarction in Persons With Prior Myocardial Infarction and Elevated Serum Low-Density Lipoprotein Cholesterol Treated With Statins Versus No Lipid-Lowering Drug for Ages 60 to 70 Years, 71 to 80 Years, 81 to 90 Years, and 91 to 100 Years

 

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  		Table 3. Stepwise Cox Regression Model for the Incidence of New Atherothrombotic Brain Infarction in Older Persons With Prior Myocardial Infarction and Increased Serum Low-Density Lipoprotein Cholesterol

 

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  		Table 5. Incidence of New Atherothrombotic Brain Infarction in Older Persons Treated With Statins for Ranges of Last Serum Low-Density Lipoprotein Cholesterol Levels

 

   Results
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 Abstract
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 Results
Discussion
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Table 1 shows the baseline characteristics of the persons treated with statins versus no lipid-lowering drug and lists levels of statistical significance. In persons treated with statins, the initial serum LDL cholesterol was 152 ± 26 mg/dl and the last serum LDL cholesterol was 98 ± 17 mg/dl (p < .0001); the initial serum HDL cholesterol was 40 ± 9 mg/dl and the last serum HDL cholesterol was 44 ± 10 mg/dl (p < .0001); and the initial serum triglycerides level was 123 ± 51 mg/dl and the last serum triglycerides level was 108 ± 45 mg/dl (p < .0001). In persons treated with no lipid-lowering drug, the initial serum LDL cholesterol was 155 ± 23 mg/dl and the last serum LDL cholesterol was 156 ± 23 mg/dl (p not significiant); the initial serum HDL cholesterol was 39 ± 9 mg/dl and the last serum HDL cholesterol was 39 ± 8 mg/dl (p not significant); and the initial serum triglycerides level was 123 ± 53 mg/dl and the last serum triglycerides level was 124 ± 51 mg/dl (p not significant).

Table 2 shows the incidence of new ABI in persons treated with statins versus no lipid-lowering drug and lists the level of statistical significance. Table 3 shows the prognostic variables for new ABI and their regression coefficients in the stepwise Cox regression model. Table 4 shows the incidence of new ABI in persons treated with statins versus no lipid-lowering drug for the age groups of 60 to 70 years, 71 to 80 years, 81 to 90 years, and 91 to 100 years and lists levels of statistical significance. Table 5 shows the incidence of new ABI in persons treated with statins with the last serum LDL cholesterol levels of <90 mg/dl, 90 to 99 mg/dl, 100 to 110 mg/dl, 111 to 120 mg/dl, 121 to 130 mg/dl, and >130 mg/dl.


   Discussion
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References
 
In the Scandinavian Simvastatin Survival Study, persons with coronary artery disease (CAD) and hypercholesterolemia treated with simvastatin had at 5.4-year median follow-up a 30% significant reduction in new stroke (1). In the Cholesterol and Recurrent Events Trial, persons aged 65 to 75 years with myocardial infarction, a serum LDL cholesterol >=115 mg/dl, and a serum total cholesterol <240 mg/dl treated with pravastatin had at 5-year median follow-up a 40% significant reduction in new stroke (2). In the Long-Term Intervention With Pravastatin in Ischaemic Disease Study, persons with myocardial infarction or unstable angina pectoris and a mean serum total cholesterol of 218 mg/dl had at 6.1-year mean follow-up a 19% significant reduction in new stroke (3).

In the present study of 1410 persons, mean age 81 years, persons with prior myocardial infarction and a serum LDL cholesterol >=125 mg/dl had at 36-month follow-up a 14% incidence of new ABI if they were treated with statins and a 26% incidence of new ABI if they were treated with no lipid-lowering drug. The significant reduction in new ABI in persons treated with statins occurred in persons aged 60 to 70 years, 71 to 80 years, and 81 to 90 years, but not in persons older than 90 years.

Significant independent risk factors for new ABI in this study were age (risk ratio = 1.04 for a 1-year increase in age), cigarette smoking (risk ratio = 3.5), systemic hypertension (risk ratio = 3.1), diabetes mellitus (risk ratio = 2.3), initial serum LDL cholesterol (risk ratio = 1.01 for each 1 mg/dl increase), initial serum high-density lipoprotein cholesterol (risk ratio = 0.97 for each 1 mg/dl increase), prior stroke (risk ratio = 2.5), and use of statins (risk ratio = 0.40). The Cochran-Armitage test showed a trend in the reduction of new ABI in persons treated with statins as the level of serum LDL cholesterol decreased (p < .0001).

Received October 30, 2001

Accepted December 3, 2001


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Scandinavian Simvastatin Survival Study Group1994. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 344:1383-1389. [Medline]
  2. Lewis SJ, Moye LA, Sacks FM, et al. 1998. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) Trial. Ann Intern Med 129:681-689. [Abstract/Free Full Text]
  3. The Long-Term Intervention With Pravastatin in Ischaemic Disease LIPID) Study Group 1998. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 339:1349-1357. [Abstract/Free Full Text]
  4. Aronow WS, Ahn C, 2002. Incidence of new coronary events in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol >=125 mg/dL treated with statins versus no lipid-lowering drug. Am J Cardiol. 89:67-69. [Medline]
  5. Aronow WS, Ahn C, Gutstein H, 1999. Risk factors for new atherothrombotic brain infarction in older African-American men and women. Am J Cardiol. 83:1144-1145. [Medline]
  6. Joint National Committee1997. The sixth report of the Joint National Committee on the detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 157:2413-2444. [Abstract]
  7. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus1997. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183-1197. [Medline]



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