Adventist health study heart disease

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When subtypes of stroke were analysed, the summary RR for vegetarians vs. Supplementary Tables 11 and 12 show results from all subgroup analyses. Although there was high heterogeneity in our main analysis as measured by I 2 , this was for CVD and IHD mainly driven by differences in the strength of the association, rather than due to differences in the direction of the association, as all studies reported risk estimates in the direction of an inverse association.

For stroke, the results were less consistent as there was heterogeneity also with regard to the direction of the association. For CVD and IHD, the inverse associations persisted in subgroup analyses stratified by sex, duration of follow-up, exclusion of early follow-up, outcome subtype, exclusion of prevalent disease at baseline, geographic location, number of cases, risk of bias and adjustment for confounding factors. In the analysis of CVD, there was little evidence of heterogeneity between subgroups, with the exception of the subgroup analysis stratified by geographic location, which showed a stronger association in North American studies than in European studies Supplementary Table In the analysis of IHD, there was also little evidence of heterogeneity between subgroups, with the exception of the subgroup analysis stratified by whether early follow-up was included or not, which showed a weaker association when early follow-up was excluded compared to when it was included Supplementary Table The null results for stroke persisted in most subgroup analyses; however, there was heterogeneity between subgroups when analyses were stratified by duration of follow-up and geographic location with inverse associations among studies with shorter vs.

To assess the impact of more rigorous adjustment on the summary estimate we conducted a sensitivity analysis using the more adjusted risk estimates adjusted for alcohol, education, exercise, and BMI in addition to age, sex and smoking status from the pooled analysis of Key et al.

The summary RR when incorporating the more adjusted estimate from the pooled analysis in our meta-analysis was 0. Using WCRF criteria for judging the evidence, we considered the overall evidence to indicate a probable protective causal association between vegetarian diets and reduced risk of CVD and IHD, and for stroke, the evidence was deemed limited-no conclusion Supplementary Table 13 and 14 , Online Resource 4 [ 36 , 37 ].

We considered the evidence on vegan diets and reduced risk of IHD to be limited-suggestive, and for CVD and stroke to be limited-no conclusion. This was mainly due to the limited number of studies and lack of precision for the association with IHD but similar effect size as for vegetarians , and weaker and less clear associations for CVD and stroke Supplementary Table 13, 14, Online Resource 4.

Detailed justifications for the judgements on vegetarian diets and CVD, IHD and stroke are outlined in Supplementary Table 13 Online Resource 4 and include, clear inverse associations based on data from eight cohort studies [ 20 , 21 , 22 , 23 , 26 , 27 ] that were robust in most subgroup and sensitivity analyses, no evidence of publication bias, and observed heterogeneity that was driven more by differences in the strength of the associations rather than differences in the direction of the associations.

There is also supporting evidence from randomized trials that vegetarian diets reduce cardiovascular risk factors, including total and LDL cholesterol [ 51 ], systolic and diastolic blood pressure [ 12 ] and weight gain [ 52 ], and there is consistent evidence that vegetarian diets reduce the risk of type 2 diabetes from cohort studies [ 53 , 54 , 55 ] see discussion for details. There is also strong evidence that consumption of several food groups, which often differ between vegetarians and nonvegetarians e.

No clear association was observed between vegan diets and CVD or stroke; however, the number of studies was limited. Although there was high heterogeneity in the main analyses for CVD and IHD, this was largely explained by differences in the strength of the associations as all studies reported risk estimates in the direction of an inverse association.

For stroke, studies were less consistent, and an inverse association was observed only among Asian studies and not in European or American studies.

There was no indication of publication bias in the three main analyses. The findings regarding IHD are consistent with previous meta-analyses [ 10 , 64 , 65 , 66 , 67 ]; however, to our knowledge this is the first meta-analysis to report a clear reduction in CVD risk overall as well, while previous meta-analyses found no association for CVD [ 10 , 65 , 66 , 67 ].

This difference is likely due to the larger sample size and greater statistical power in the current analysis. Our finding of no association for stroke is consistent with previous meta-analyses on vegetarian diets and total stroke or cerebrovascular disease [ 10 , 64 , 65 , 66 , 67 ].

However, considering the results of the influence analysis, we cannot entirely rule out a weak to moderate inverse association, but further larger studies are needed to clarify this. Our analysis has several limitations as well as strengths. Although the meta-analysis was not registered with a pre-defined analysis plan or study protocol, the analysis used a similar format to previous meta-analyses [ 61 , 62 , 63 ] and efforts were made to ensure transparency of the work.

Although the title and abstract screening was only performed by one author JSD , the second part full-text assessment was performed by two authors JSD, DA. Heterogeneity was an apparent issue across all outcomes. However, heterogeneity is expected for a number of reasons, including differences in the 1 detail of the dietary assessment methods used, 2 geographic location and background food choices and dietary patterns [ 21 ], 3 confounders that were adjusted for in the statistical analyses, 4 sample size and duration of follow-up, and 5 stability of the diet over time in different studies.

In contrast, results for stroke were less clear and somewhat inconsistent, and there was heterogeneity between subgroups in the subgroup analyses stratified by geographic location with an inverse association in Asian studies, but no clear association was observed in North America or Europe. Whether these differences in results are due to differences in dietary habits between the Asian and the US and European studies, or whether it is simply a play of chance is unclear.

Further studies are therefore needed to clarify this association and to explain the potential geographic variations in the results. Vegetarians are often more health-conscious than nonvegetarians, and given the observational design of the included studies, confounding from other lifestyle factors could be an issue.

However, the results persisted across multiple subgroup analyses of studies that adjusted for age, education, alcohol, smoking, BMI and physical activity, and there was little indication of heterogeneity between these subgroups.

In a pooled analysis, further adjustment for alcohol, education, exercise and BMI in addition to adjustment for age, sex, and smoking status made little impact on the association between vegetarian diets and IHD [ 20 ], and when we used the more adjusted results from this pooled analysis there was also little change in the summary estimates, suggesting little confounding from these factors.

Although residual confounding could be an issue, the inverse association between vegetarian diets and IHD persisted across strata of smoking and the presence of other risk factors in the EPIC-Oxford study, and inverse associations were also observed in the Adventist Health and Mortality Studies, populations consisting largely of non-smokers and non-alcohol drinkers, which might suggest an independent effect of a vegetarian diet on risk of IHD and CVD [ 20 , 21 , 23 ].

The results also persisted across strata of risk of bias and there was no between subgroup heterogeneity detected with meta-regression analyses. Although publication bias can affect meta-analyses of published studies, we found no indication of publication bias with the statistical tests used or by inspection of the funnel plots.

The definitions of vegetarian and nonvegetarian diets were not entirely uniform across studies, and it is possible that this could have affected the results; however, we do not expect a substantial impact of this on the overall results.

In most studies, vegetarian status was defined based on meat and fish consumption reported on food frequency questionnaires, while in the Health Food Shoppers Study [ 26 ] participants were asked whether they identified as vegetarians or nonvegetarians. Nevertheless, exclusion of this study did not materially alter any of the observed associations, suggesting little impact of this study on the overall conclusions.

Meat consumption has been reported to be markedly lower among the nonvegetarians in the Adventist Health Study 2 [ 68 , 69 ], EPIC-Oxford [ 70 ], and the UK Biobank [ 71 ] when compared to the general population [ 72 , 73 ].

If differences in meat consumption account for some of the difference in cardiovascular risk between vegetarians and nonvegetarians, this could potentially lead to conservative estimates of the true associations compared to if a more representative comparison group had been available.

This could lead to misclassification of dietary habits, which given the prospective design of the studies, would likely be non-differential and might bias the summary estimates toward the null. In the EPIC-Oxford study, there was little difference in the hazard ratios by whether repeated measures or only baseline data were used to analyse the association between vegetarian diets and IHD [ 23 ].

However, other studies have reported considerable differences in the association between red and processed meat intake and CVD mortality when comparing repeated measures vs. The stability of vegetarian status or meat consumption over time could differ between studies, but further studies are needed to address this question.

The current analysis was not able to assess the association between quality of vegetarian or vegan diets and CVD, IHD or stroke risk, as there were no studies that have investigated this directly to date.

Other studies that have assessed the association between plant-based dietary indices and CVD risk have reported inverse associations between plant-based dietary indices overall as well as for healthy plant-based dietary indices characterized by high intake of whole plant foods and CVD risk, while unhealthy plant-based dietary indices characterized by high intake of sugar-sweetened beverages, French fries, chips, cookies, and other fast foods have been associated with increased CVD risk [ 74 ], suggesting the importance of emphasizing whole plant foods.

Strengths of our meta-analysis include the following: 1 the detailed search strategy; 2 rigorous and comprehensive risk of bias assessments that more adequately assess internal validity of the included studies ROBINS-I [ 30 , 31 , 33 , 34 ], with results implemented in synthesis through subgroup analyses; 3 increased sample size and statistical power which allowed detection of moderate associations between vegetarian diets and both CVD and IHD and 4 the detailed subgroup and sensitivity analyses, which supported the robustness of the findings.

The current findings are consistent with other epidemiological and experimental studies which have found that vegetarians have a lower BMI [ 10 ] and reduced weight gain [ 52 , 75 ], lower serum total and LDL-cholesterol [ 51 ], lower blood pressure or prevalence of hypertension [ 12 , 13 , 14 ] and lower risk of type 2 diabetes [ 16 ] than nonvegetarians, all of which are important cardiovascular risk factors.

Meta-analyses of randomized trials reported a 0. Differences in adiposity and type 2 diabetes risk could also contribute towards a lower IHD risk; however, some of the difference in LDL-cholesterol and systolic blood pressure, as well as a sizeable part of the reduction in risk of type 2 diabetes among vegetarians versus nonvegetarians, is likely driven by differences in BMI.

In the current analysis, adjustment for BMI attenuated the association between vegetarian diets and IHD by approximately one-fifth, suggesting a modest part of the difference in IHD risk might be mediated by differences in BMI.

Several cohort studies have shown an increased risk not only of both CVD and IHD [ 56 , 57 , 58 , 59 , 60 ], but also for stroke associated with consumption of red and processed meat [ 78 ]. Red and processed meat are major sources of dietary saturated fat and cholesterol, which are known to increase serum cholesterol [ 79 ] and could thereby increase the risk of IHD. Experimental studies in mice have also shown that red meat increases atherosclerosis by increasing the production of trimethylamine-N-oxide TMAO through a gut-dependent pathway [ 80 ].

In addition, processed meats are a major source of salt, which could increase CVD risk through increased blood pressure [ 81 ], and both red and processed meat intake have been associated with increased weight gain [ 82 ] and type 2 diabetes [ 83 ], which could increase CVD risk.

However, other dietary differences could also contribute toward reduced CVD risk among vegetarians. Compared to meat-eaters, vegetarians tend to have a higher intake of fruit and vegetables, whole grains, nuts, and legumes [ 70 ], and such food groups have generally been shown to reduce the risk of CVD, IHD and stroke [ 61 , 62 , 63 ] and to have benefits on cardiovascular risk factors such as blood pressure [ 84 , 85 , 86 ], serum cholesterol [ 87 , 88 , 89 ], bodyweight [ 82 ] and risk of type 2 diabetes [ 90 , 91 ].

The present meta-analysis suggests a vegetarian diet offers important health benefits by reducing the risk of both CVD and IHD, although not stroke.

These are findings with important public health implications given that CVDs still are the leading causes of death and disease globally and suggest that adoption of plant-based dietary patterns such as vegetarian diets can be useful for reducing the CVD burden.

These findings support a stronger emphasis on vegetarian dietary patterns in public health recommendations as a measure for CVD prevention. Future research should focus on additional large-scale and high-quality studies as they are needed to clarify results for stroke and stroke subtypes, as well as to provide results stratified by other risk factors and results with adequate adjustment for confounding factors to better rule out potential residual confounding.

Further studies from other geographic regions are also needed. Detailed and repeated dietary assessments may be important to take into account dietary changes during follow-up. Future studies should focus on recruiting more vegans as there were few studies with sufficient numbers to detect a clear association among the vegans. These findings are consistent with existing guidelines recommending plant-based dietary patterns for CVD prevention but suggest more emphasis may be put on vegetarian diets.

Further studies are needed to clarify the association between vegetarian diets and stroke risk, as well as the association between vegan diets and CVD, IHD and stroke. Data, material and analytical code will be made available upon reasonable request. Lancet � Article Google Scholar. J Am Coll Cardiol 76 25 � Article PubMed Google Scholar. Circulation 11 :e�e Helsedirektoratet Kostraad ved primaer- og sekundaerforebygging av hjerte- og karsykdom Dietary advice for primary and secondary prevention of cardiovascular disease.

Oslo: Helsedirektoratet. Accessed Feb 20, ]. Available at:. Eur Heart J 42 34 � Najjar RS, Moore CE, Montgomery BD A defined, plant-based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications. Clin Cardiol 41 3 � Nutr Rev 75 9 � Crit Rev Food Sci Nutr 57 17 � J Am Heart Assoc 4 10 :e Public Health Nutr 5 5 � Public Health Nutr 15 10 � Diabetes Care 32 5 � Am J Clin Nutr 81 6 � Br J Nutr 8 � Public Health Nutr 6 3 � Eur Heart J 42 12 � BMJ Neurology 96 15 :e�e Neurology 94 11 :e�e Public Health Nutr 5 1 � Cancer Epidemiol Biomarkers Prev 14 4 � Environ Int Pt 1 � PLoS Med 16 2 :e BMJ i University of Bristol Preliminary risk of bias for exposures tool template.

Environ Int � Eur J Nutr 60 6 � Accessed Feb 26, ]. Judging the evidence. Available at: dietandcancerreport. Control Clin Trials 7 3 � Stat Med 21 11 � BMJ � Biometrics 50 4 � Google Scholar. Ann Intern Med 4 � Am J Clin Nutr 1 � The Adventist Health Study.

Am J Epidemiol 7 � Prev Med 13 5 � Cancer 64 3 � Am J Clin Nutr 36 5 � Clin Nutr 39 11 � J Acad Nutr Diet 6 � Lee Y, Park K Adherence to a vegetarian diet and diabetes risk: a systematic review and meta-analysis of observational studies. Nutrients 9 6 Am J Public Health 75 5 � Nutr Diabetes 9 1 BMJ m Circulation 9 � BMJ j Arch Intern Med 7 � BMC Med 19 1 Int J Epidemiol 46 3 � BMC Med 14 1 Am J Prev Cardiol Ann Nutr Metab 60 4 � Front Nutr Int J Cardiol 3 � Nutrients 11 3 Br J Nutr 10 � Nutrients 11 4 However, the Adventist Health Study has gone an important step further in collecting data on both fatal and non-fatal cases of coronary heart disease.

For fatal cases of coronary heart disease, the older Adventist Mortality Study found that the mortality rates for Adventist men in particular were only 66 percent as compared to their non-Adventist counterparts. When compared only to non-smoking non-Adventists, the figure rose to 76 percent.

Differences for women were less impressive. Studies of risk factors associated with coronary heart disease in Adventists have also been done since the early s. Typically, serum cholesterol levels have been shown to be significantly lower for Adventists when compared to non-Adventists. Actual levels have generally been at least 10 to 30 milligrams per deciliter lower. More recently, Dr. Fraser and his colleagues looked at randomly selected, middle-aged Adventist men and a similarly-aged non-Adventist group of neighbors in Southern California.

This was one of only a few studies to look at lipoprotein subfractions in Adventists. Their findings:. Though the ratio between the HDL and LDL levels was similar, the differences in levels of the component lipoproteins were highly statistically significant. It is noted that lower levels of HDL cholesterol are characteristic of populations with lower fat intakes.

The risk meaning of this lower level in vegetarians is unknown. Some controversy surrounds the risk factor of high blood pressure in vegetarians. However, both Adventist and non-Adventist vegetarians probably experience a reduction of 4 to 5 millimeters systolic and 2 to 3 millimeters diastolic, considered to be a relatively minor difference. The risk factor of little or no exercise has not been studied to any great extent in Adventists.

However, the Southern California study included the following question: "How many times each week do you exercise enough to provoke a sweat? In this case, the difference in exercise habits was highly statistically significant.

The risk factor of obesity has also received very little attention in Adventists. However, in the previously mentioned study, Quetelet index of obesity in Adventists showed very little difference from their non-Adventist neighbors. It has been argued that Adventist populations are so unique in their lifestyles that none of the findings can be accurately applied to general non-Adventist populations.

To counter that argument, researchers investigated associations between heart disease and factors such as age, sex, diabetes mellitus, hypertension, smoking, physical activity and obesity in the Adventist Health Study population. Using several statistical models, they found these risk factors had the same role in predicting heart disease among Adventists as had been repeatedly shown in non-Adventist populations.

When comparing the sexes, heart attack risks were similar to those of non-Adventist populations. The risk was 2. Answers to the dietary questions in the survey also provided some new findings about the Adventist population.

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