CTF Structured Abstract: Lowering blood total cholesterol

Canadian Task Force on Preventive Health Care

Structured Abstract

Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made. (Formerly, these situations were captured under a "C Recommendation".) This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade. For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.

Lowering the Blood Total Cholesterol Level to Prevent Coronary Heart Disease

Prepared by Alexander G. Logan, MD, FRCPC, Professor of Medicine, University of Toronto, Ontario

These recommendations were finalized by the Task Force in June 1994

Objective
Burden of Suffering
Options
Outcomes

Evidence
Values
Benefits, Harms, and Costs
Recommendations

Validation
Sponsors
Selected References

Objective

To make recommendations for routine cholesterol screening, drug treatments, and dietary advice on fats for asymptomatic Canadian adults (primary prevention). This guideline is an update of the 1993 and 1979 Canadian Task Force reports.

Burden of Suffering

Although the death rate from coronary heart disease (CHD) in Canada has decreased by almost 40% over the past 15 years, cardiovascular disease, the primary cause of premature death in most industrialized countries, still accounts for more than 40% of all deaths in Canada. Most of these deaths were from CHD. An increased blood cholesterol level, specifically a high low-density lipoprotein (LDL) cholesterol, is closely linked to the severity of atherosclerosis in the coronary arteries and is a major risk predictor of clinical CHD. There is also increasing evidence from epidemiologic studies that other cholesterol subfractions (high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C), the carrier apolipoproteins of cholesterol and a -lipoprotein) may help to predict the risk of myocardial infarction.

Although the risk of CHD is strongly related to the serum total cholesterol level, at any level of cholesterol the risk varies widely depending on the presence of other risk factors such as elevated systolic blood pressure, left ventricular hypertrophy, and smoking.

In the context of routine clinical practice the use of the serum total cholesterol level to predict future CHD events in individual patients is not straightforward. Thus, the serum cholesterol level is a poor discriminator between people destined to have symptomatic CHD and those who will remain symptom-free. It is this weak predictive power that has been a source of concern about recommending universal screening.

Options

Cholesterol screening can include total cholesterol or selective lipoprotein analysis. Treatment options can either be dietary (reductions in total fat, cholesterol, or calories or a combination of all 3) or pharmacologic (bile acid sequesterants, nicotinic acids, niacin, fibric acid derivatives, probucol, estrogens, 3-hydroxy-3-methylglutaryl-coenzyme A [HMG CoA] reductase inhibitors). No screening is also an option.

Outcomes

Cholesterol levels, mortality (cardiac, noncardiac, cancer, violence, and total) and improved diets.

Evidence

MEDLINE was searched for 1979 to 1991 using the MeSH heading cholesterol with subheadings complications, diagnosis, drug therapy, epidemiology, prevention and control, and therapy. Bibliographies of studies and review articles were also checked. Studies and reviews available from 1991 to 1994 were added to the current report.

Study results were synthesized in table or graphic format and using the Mantel Haenszel method to combine the data for overall risks and benefits. Data from women were insufficient for combining.

Recommendations were graded as:

A Good evidence to support the recommendation that the condition be specifically considered in a PHE.

B Fair evidence to support the recommendation that the condition be specifically considered in a PHE.

C Poor evidence regarding inclusion or exclusion of the condition in a PHE, but recommendations may be made on other grounds.

D Fair evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

E Good evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

Quality of evidence was rated according to 5 levels:

I Evidence from at least 1 properly randomized controlled trial (RCT).

II-1 Evidence from well-designed controlled trials without randomization.

II-2 Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 centre or research group.

II-3 Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here.

III Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.

Values

The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs

Screening for total blood cholesterol produces many false positive and false negative results which can be reduced by repeat measurement, or by selective lipoprotein analysis. Few or no adverse effects result from individuals assuming falsely that they have high cholesterol levels.

6 RCTs examined the effect of reductions in serum cholesterol on coronary heart disease and 1 RCT examined the safety and efficacy of a lipid-lowering drug. Combined data on primarily asymptomatic middle-aged men in 5 drug and 2 diet trials indicated a significant decrease in nonfatal cardiac events (odds ratio [OR] 0.74, 95% CI 0.64 to 0.85), a significant increase in noncardiac mortality (OR 1.19, CI 1.03 to 1.30), an insignificant increase in all-cause mortality (OR 1.10, CI 0.99 to 1.22) and an insignificant decrease in cardiac mortality (OR 0.90, 95% CI: 0.71 to 1.14). Analysis of pooled data for 38 940 men and women found similar results. These findings are consistent with those of 2 other meta-analyses.

Short-term efficacy and safety of lipid-lowering drugs has been established only for middle-aged men with high cholesterol levels. Adverse effects vary by drug type. Long-term safety is unknown. No drug trials involving children, young adults, and elderly adults were identified and data on women were limited.

No evidence exists from primary prevention trials that dietary modification reduces risk for coronary heart disease. Findings with respect to cardiac, noncardiac and all cause mortality are similar to those described for drug and combined therapy data. Data from 6 community cohort studies involving primarily men aged 30 to 69 years indicated that a possible association exists between risk for coronary heart disease mortality and baseline dietary score, cholesterol and saturated fatty acid intake and a negative association with polyunsaturated fatty acid and fibre intake.

Using data from a drug trial, the number of patients needed to be treated for 5 years to prevent 1 additional fatal or nonfatal cardiac event among individuals at low or moderate risk (blood cholesterol Ł 6.85 mmol/L) was estimated to be 356.

Recommendations

Recommendation grade [A, B, C, D, E] and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

There is insufficient evidence to include or exclude, from the PHE for asymptomatic adults, measurement of serum total cholesterol [C, III]
There is fair evidence to treat men 30 to 59 years of age who have high cholesterol, with a stepped-fat modified diet to which a cholesterol-lowering drug is added if response if is inadequate [B, I]. For other asymptomatic persons, there is insufficient evidence to recommend treatment [C, III].
There is fair evidence to give men 30 to 69 years of age general dietary advice on fat (especially saturated fat) during the PHE [B, II-2]. For all other adults, there is insufficient evidence to give dietary advice on fats during the PHE [C, III].
Screening or case finding (among those who visit a physician’s office) should be considered for men aged 30 to 59 years [C, III]. The total cholesterol level should be the initial screening test.

Validation

This report was externally peer-reviewed. Recommendations and background papers were sent for external peer review. The Canadian Consensus Conference on Cholesterol, the United States National Cholesterol Education Program, and the American Heart Association have recommended dietary therapy as first-line treatment for high cholesterol levels. The Canadian Cholesterol Consensus Conference recommends case finding in adults with particular attention to those with cardiac risk factors. The United States National Cholesterol Education Program recommends that HDL-cholesterol measurement be done along with screening for those with high risk factors for coronary heart disease. The Toronto Working Group on Cholesterol Policy recommends a case-finding strategy.

Selected References

Source Document

Logan A.G. Lowering the blood total cholesterol level to present coronary heart disease. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 650-69.

Other

Canadian Task Force on the Periodic Health Examination: The periodic health examination, 1993 update: 2. Lowering the blood total cholesterol level to prevent coronary heart disease. Can Med Assoc J. 1993;148:521-38.

Link to Full Text of this review

Link to Summary Table of Recommendations of this review

Link to Selected References list of this review

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A	Good evidence to support the recommendation that the condition be specifically considered in a PHE.
B	Fair evidence to support the recommendation that the condition be specifically considered in a PHE.
C	Poor evidence regarding inclusion or exclusion of the condition in a PHE, but recommendations may be made on other grounds.
D	Fair evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.
E	Good evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

I	Evidence from at least 1 properly randomized controlled trial (RCT).
II-1	Evidence from well-designed controlled trials without randomization.
II-2	Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 centre or research group.
II-3	Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here.
III	Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.