Dietary Patterns, Alcohol Consumption and Risk of Coronary Heart Disease in Adults: A Meta-Analysis

Previous studies reported the potential associations between dietary patterns and the risk of coronary heart disease (CHD) in adulthood, however a consistent perspective has not been established to date. Herein, we carried out this meta-analysis to evaluate the associations between dietary patterns and the risk of CHD. MEDLINE and EBSCO were searched for relevant articles published up to April 2015. A total of 35 articles (reporting 37 original studies) met the inclusion criteria and were included in the present meta-analysis. The decreased risk of CHD was shown for the highest compared with the lowest categories of healthy/prudent dietary patterns (odds ratio (OR) = 0.67; 95% confidence interval (CI): 0.60, 0.75; p < 0.00001) and alcohol consumption (OR = 0.68; 95% CI: 0.59, 0.78; p < 0.00001). There was evidence of an increased risk of CHD in the highest compared with the lowest categories of the unhealthy/Western-type dietary patterns (OR = 1.45; 95% CI: 1.05, 2.01; p = 0.02). The results of this meta-analysis indicate that different dietary patterns may be associated with the risk of CHD.

ratio (OR) for dietary patterns in highest categories compared with lowest categories. Raw data from individual studies were weighted and combined to produce an overall OR. Publication bias was assessed by inspection of the funnel plot and by formal testing for "funnel plot" asymmetry using Begg's test and Egger's test [27]. All statistical tests were two-sided and p values less than 0.05 were considered significant.

Overview of Included Studies for the Systematic Meta-Analysis
An electronic literature search in the database of MEDLINE and EBSCO identified 560 studies, 525 of which were excluded based on the reasons listed in Figure 1: meta-analysis, reviews or systematic reviews (n = 173); title and abstract did not contain the data on classification of dietary pattern or alcohol consumption (n = 278); did not provide sufficient dichotomous data on dietary pattern and CHD (n = 25); focused on single nutrients or food (n = 18); did not provide the data about percent of CHD or number of each group (n = 20); reported data using different alcohol consumption categories (n = 10); and reported the same data (n = 1). At last, 35 articles [8,11,[13][14][15][16][17][18][19][20][21][22][23] (reporting 37 original studies) met the inclusion criteria and were included in this meta-analysis. Descriptive information of each included study was presented in Table 1.

Western-Type Dietary Pattern
The unhealthy/Western-type dietary patterns were characterized by high consumption of red and/or processed meat, refined grains, sweets, high-fat dairy products, butter, potatoes and high-fat gravy, and low intakes of fruits and vegetables. The studies under consideration labeled it as "Western" [8,9,[13][14][15]23,28], "Animal foods" [17,22,30] and "Dietary pattern 2" [19]. The association between unhealthy/Westerntype dietary patterns and the risk of CHD was shown in Figure 3. There was evidence of an increased risk of CHD in the highest compared with the lowest categories of unhealthy/Western-type dietary patterns (OR = 1.45; CI: 1.05, 2.01; p = 0.02) where all studies were combined in the random-effects model. There was significant heterogeneity (I 2 = 96%, p < 0.00001).

Western-Type Dietary Pattern
The unhealthy/Western-type dietary patterns were characterized by high consumption of red and/or processed meat, refined grains, sweets, high-fat dairy products, butter, potatoes and high-fat gravy, and low intakes of fruits and vegetables. The studies under consideration labeled it as "Western" [8,9,[13][14][15]23,28], "Animal foods" [17,22,30] and "Dietary pattern 2" [19]. The association between unhealthy/Western-type dietary patterns and the risk of CHD was shown in Figure 3. There was evidence of an increased risk of CHD in the highest compared with the lowest categories of unhealthy/Western-type dietary patterns (OR = 1.45; CI: 1.05, 2.01; p = 0.02) where all studies were combined in the random-effects model. There was significant heterogeneity (I 2 = 96%, p < 0.00001).

Alcohol Consumption
The alcohol consumption was characterized by moderate intakes of wines, alcohol-containing beers, and white spirits. Nineteen studies (reporting twenty original studies) have identified moderate alcohol consumption. The data from nineteen studies were assessed using the random-effects model, and there was significant heterogeneity (I 2 = 83%, p < 0.00001). Figure 4 showed an obvious evidence of a decreased risk of CHD in the moderate drinking compared with non-drinking category intake of the alcohol consumption levels (OR = 0.68; 95% CI: 0.59, 0.78; p < 0.00001).

Alcohol Consumption
The alcohol consumption was characterized by moderate intakes of wines, alcohol-containing beers, and white spirits. Nineteen studies (reporting twenty original studies) have identified moderate alcohol consumption. The data from nineteen studies were assessed using the random-effects model, and there was significant heterogeneity (I 2 = 83%, p < 0.00001). Figure 4 showed an obvious evidence of a decreased risk of CHD in the moderate drinking compared with non-drinking category intake of the alcohol consumption levels (OR = 0.68; 95% CI: 0.59, 0.78; p < 0.00001).

Alcohol Consumption
The alcohol consumption was characterized by moderate intakes of wines, alcohol-containing beers, and white spirits. Nineteen studies (reporting twenty original studies) have identified moderate alcohol consumption. The data from nineteen studies were assessed using the random-effects model, and there was significant heterogeneity (I 2 = 83%, p < 0.00001). Figure 4 showed an obvious evidence of a decreased risk of CHD in the moderate drinking compared with non-drinking category intake of the alcohol consumption levels (OR = 0.68; 95% CI: 0.59, 0.78; p < 0.00001).

Publication Bias
Inspection of funnel plots did not reveal evidence of asymmetry (Appendix A). Begg's tests for publication bias were not statistically significant (highest compared with lowest category: healthy/prudent dietary pattern, Begg's test p = 0.285; unhealthy/Western-type dietary pattern, Begg's test p = 0.276; and alcohol consumption, Begg's test p = 0.218).

Discussion
Limited epidemiological research has reported the associations between dietary patterns and the risk of CHD. To our knowledge, this is the latest meta-analysis evaluating the evidence for dietary patterns and CHD risk. In the present study, we have an update on the earlier systematic review (Li et al., and Hou et al., 2014) [50,51] and further explore the association between moderate alcohol consumption and the risk of CHD. The results of this meta-analysis demonstrate that the healthy/prudent dietary patterns and moderate alcohol consumption may decrease the risk of CHD, whereas unhealthy/Western-type dietary patterns may increase the risk of CHD. Our findings have confirmed the associations between different dietary patterns and the risk of CHD, and provided information that may be translated into public health action for primary prevention of CHD.
In our analyses, the healthy/prudent dietary patterns were associated with a reduced risk of CHD. Our results were in agreement with some previous studies, which reported an inverse association between healthy/prudent dietary patterns and the risk of CHD [11,23]. The apparently protective effect of vegetables, and fruits may be related to high concentration of antioxidant substances (e.g., vitamin C, vitamin E, and other carotenoids compounds). A previous meta-analysis of fruit and vegetables consumption and risk of CHD concluded that high intakes of fruit and vegetables were associated with a decreased risk of CHD [52]. Besides, several studies have also indicated that antioxidants such as vitamin E can slow the rate of oxidation, protecting endothelial cells and vascular [53], thereby reducing the risk of CHD. Furthermore, earlier studies have found that higher intake of folate may decrease the concentration of homocysteine, which may increase the risk of CHD [53,54]. Recently, Pereira et al. reported an inverse association between dietary fiber and the risk of CHD [55]. To our knowledge, the possible mechanism is that dietary fiber can modify blood lipid profiles, lower blood pressure, as well as reduce blood glucose concentrations by slowing intestinal absorption [56]. In addition, some clinical and biological investigations have also found that the micro-and macro-constituents of fruit and vegetables may decrease the risk of hypertension, dyslipidemia and diabetes, which are considered as having an important role in the development or progression of CHD [57,58].
The unhealthy/Western-type dietary patterns were associated with an increased risk of CHD in this meta-analysis. Our results were consistent with previous studies [17,19], which indicated that red meat and processed meat consumption were associated with an increased risk of CHD. To our knowledge, there are several plausible explanations for the positive association between Western-type dietary patterns and CHD risk. Firstly, high consumption of red and processed meat is associated with raised total cholesterol, LDL-cholesterol and blood pressure, and greater BMI [59]. As mentioned above, these metabolic changes are related with the risk factors for CHD. Secondly, high temperature commercial cooking or frying, commonly used in preparing processed meats, may generate heterocyclic amines or polycyclic aromatic hydrocarbons, which may increase the risk of CHD and DM [60,61]. Finally, processed meats contain a high content of salt, nitrates and their byproducts (e.g., peroxynitrite), which may be associated with an increased risk of CHD [62].
An inverse association was shown for moderate alcohol consumption and the risk of CHD in our analyses. Previously, a meta-analysis of alcohol consumption and the risk of CHD indicated that moderate alcohol-drinking (ď1.5 drinks/day) was associated with a decreased risk of CHD [63]. In fact, alcohol consumption has been consistently considered an important risk for some chronic diseases, including hypertension and diabetes. Nevertheless, our results found the favorable effect of moderate alcohol consumption on the development of CHD. As we all know, moderate alcohol consumption can raise the concentration of serum high density lipoprotein cholesterol, which may protect against atheroma formation in coronary arteries [64,65]. In addition, it is also associated with the increased vascular wall prostacyclin, thus preventing thrombus formation in coronary arteries [66]. Furthermore, some studies have found that light to moderate alcohol consumption can lower the levels of fasting insulin [67], which is related to the decreased risk of CHD.

Strengths and Limitations
This meta-analysis has its own strengths and limitations. Firstly, this is the latest meta-analysis reporting the associations between dietary patterns and the risk of CHD. We not only have an update on an earlier systematic review (Li et al. and Hou et al., 2014) [50,51], but also further explore the association between moderate alcohol consumption and the risk of CHD. Secondly, the cases of CHD were confirmed based on clinical manifestations, electrocardiogram, and coronary arteriography, avoiding misdiagnosis. Thirdly, no signs of publication bias were evident in the funnel plot, and the statistical test for publication bias was non-significant. However, some limitations should also be mentioned, when interpreting the results of this meta-analysis. Firstly, the principal limitation of this study was the use of potentially biased evidence. Moreover, there was an inconsistent adjustment for potential confounders among the included studies, and we did not exclude the possibility of confounding in this meta-analysis. As a result, the data included in our analyses might suffer from differing degrees of completeness and accuracy. Secondly, ten of thirty-six studies are case-control studies in this meta-analysis. Thus, selection bias is inevitable in our analyses.

Conclusions
In conclusion, results from this meta-analysis indicate that healthy/prudent dietary patterns and moderate alcohol consumption are associated with a decreased risk of CHD, while unhealthy/Western-type patterns are associated with an increased risk of CHD. In addition, these findings also suggest that a change of diet is essential for the prevention of CHD. Herein, it makes sense to elucidate the potential associations between dietary patterns and the risk of CHD, and provide scientific rationale for formulating dietary guidelines. Further studies are required to confirm the causal associations between dietary patterns and the risk of CHD.        [11] * * * * * * * * ******** Fitzgerald et al., 2012 [20] * * * * Figure A3. Funnel plots for CHD in the moderate drinking compared with non-drinking category intake of "alcohol consumption" pattern in all studies.
Appendix B Table B1. Assessment of study quality.