A 62-year-old woman is unable to tolerate drug therapy for hyperlipidemia. A 24-hour dietary recall reveals a diet high in saturated fat.
Is there benefit in recommending that patients at risk of cardiovascular disease lower the amount of saturated fat in their diet?
Reducing or modifying the amount or type of fat in a patient's diet and replacing it with polyunsaturated fats will not significantly reduce the risk of death from all causes of cardiovascular disease but could reduce the risk of an important cardiovascular disease event by 16 percent. If a patient remained on a reduced- or modified-fat diet for at least two years, the risk of an important cardiovascular event could be reduced by 24 percent. For one patient to benefit at one year, 156 patients similar to the patient in this clinical scenario would have to be treated with a reduced- or modified-fat diet.
Background. Reduction or modification of dietary fat can improve total cholesterol levels but may have a variety of positive and negative effects on other cardiovascular factors.1
Objectives. The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality, and cardiovascular morbidity, over at least six months, using all available randomized clinical trials.
Search Strategy. The Cochrane Library, MEDLINE, EMBASE, CAB Abstracts, a CVRCT registry, and related Cochrane Groups' trial registers were searched through the spring of 1998; SIGLE was searched to January 1999. Trials known to experts in the field and bibliographies were included through May 1999.
Selection Criteria. Trials fulfilled the following criteria: (1) randomized with an appropriate control group; (2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions); (3) not multifactorial; (4) healthy adult humans; (5) intervention duration of at least six months; and (6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, and disagreements were resolved by discussion or a third party.
Data Collection and Analysis. Rate data were extracted by two independent reviewers, and meta-analysis was performed using random effects methodology. Meta-regression and funnel plots were used.
Primary Results. Twenty-seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio, 0.98; 95 percent confidence interval [CI], 0.86 to 1.12); a trend toward protection from cardiovascular mortality (rate ratio, 0.91; 95 percent CI, 0.77 to 1.07) was seen, as well as significant protection from cardiovascular events (rate ratio, 0.84; 95 percent CI, 0.72 to 0.99). The latter two factors become nonsignificant on sensitivity analysis.
Trials where participants were involved for longer than two years showed significant reductions in the rate of cardiovascular disease events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high- and low-risk groups but was statistically significant only in the former group.
Reviewers' Conclusions. The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years' duration. Lifestyle advice to all those at high risk of cardiovascular disease (especially if statins are unavailable or rationed) and to lower-risk population groups should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturated fats.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org)
Did the authors address a focused clinical question? Yes.
Were the criteria used to select articles for inclusion appropriate? Yes, randomized clinical trials with dietary invention aimed at saturated fats.
Is it likely that important relevant articles were missed? No, search criteria were well articulated, and funnel plot did not reveal any publication bias.
Was the validity of the individual articles appraised? Yes.
Were the assessments of studies reproducible? Yes, the kappa score of 0.61 demonstrates moderately strong reproducibility.
Were the results similar from study to study? Yes, all tests of heterogeneity were “not significant,” suggesting homogeneous results.
Can the results be applied to patient care? Yes.
Do the conclusions make biological and clinical sense? Yes.
Are the benefits worth the harms and cost? Yes; little harm is found with the diet suggested, and the costs are limited.
For several decades, the classic diet-heart hypothesis focusing on reducing saturated fats and replacing them with polyunsaturated fats has resulted in more than 200 clinical trials demonstrating a modest decrease in serum cholesterol levels and other cardiovascular risk factors with these dietary interventions. The underlying assumption in these trials is that improvement in risk-factor profiles would translate to improved clinical outcomes related to cardiovascular disease, as has been found in numerous observational studies.
This meta-analysis assessed 27 trials that evaluated the classic dietary hypothesis and its direct effect on clinically relevant outcomes of total mortality, cardiovascular disease mortality, and cardiovascular disease outcomes. Meta-analysis showed a modest benefit in reduction of cardiovascular events, but not in reduction of total mortality or cardiovascular mortality. Subgroup analysis showed improved outcomes if the study lasted longer than two years and a trend toward greater benefit if the intervention lowered serum cholesterol levels or resulted in a greater degree of total fat lowering. However, the latter two trends did not reach statistical significance.
Over the past decade, the atherogenic effects of trans fatty acids3,4 and the important role of monounsaturated fats (Mediterranean diets)5 and n-3 polyunsaturated fatty acids (fatty fish)6 have suggested that diets other than those replacing saturated fats with n-6 polyunsaturated fats may be more effective than the diets tested in this meta-analysis. In addition, the important role of folic acid and B vitamins in relation to hyperhomocystinemia,7 a new cardiovascular risk factor, and the potentially important role of antioxidants such as vitamin E8 and flavinoids9 make clinical recommendations about the best diet for patients with cardiovascular disease a matter subject to debate.
|Reading the Numbers|
|In scientific experiments, precise, reproducible results lead to a reduction of measurement error and, therefore, increase the validity of the experimental findings. An entire field of statistics has been formulated to estimate validity based on the reproducibility of results. For dichotomous outcomes such as agree/disagree on chart abstraction by two observers, a measurement of agreement is the kappa statistic.2 This statistic is a ratio of actual agreement beyond chance/potential agreement beyond chance. If two observers agree 97 percent of the time and the expected agreement by chance was 91 percent, then the kappa score would be 0.97 − 0.91/1.0 − 0.91 = 0.06/0.09 = 0.67. Thus, 1 is complete agreement, zero is no agreement, and −1 is complete disagreement. A value of zero to 0.3 is mild agreement, 0.31 to 0.6 is moderate agreement, and 0.61 to 1.00 is strong agreement.|
|Examples of kappa scores are 0.67 for mammogram interpretation by two radiologists, 0.3 for electrocardiogram (ECG) interpretation by two cardiologists, and 0.61 for the same cardiologist reading the same ECG twice. Thus, the kappa of 0.61 found in this Cochrane review suggests moderately strong agreement between the two reviewers.|
Further clinical trials into the optimal diet necessary to reduce cardiovascular disease and increase longevity are needed before definitive dietary recommendations can be made with confidence. Until that time, reducing the saturated fat content in a patient's diet appears to be reasonable.