Mediterranean diet dec CAD and biomarkers, etc

A recent study found that those adhering to a higher Mediterranean diet had fewer cardiovascular events, apparently mediated by decreased inflammatory markers (see cad women mediterranean diet jama2018 in dropbox, or doi:10.1001/jamanetworkopen.2018.5708)

Details:

-- 25,994 women in the Women’s Health Study were followed for up to 12 years

    -- baseline data were collected from 1993 to 1996, analysis from 2017 to 2018

-- diet was evaluated in terms of degree of coherence with the typical Mediterranean diet (9 specific categories), into 3 groupings:

    -- 39% were in the low Mediterranean diet group, 36% in the middle, and 25% in the upper

-- at baseline: mean age 53, but the following tracked with Mediterranean diet group: current smoking (16% in the low MED diet vs 6% in the highest), exercise, alcohol consumption (which was higher the high Mediterranean group), all of the subgroups of dietary consumption (veges, etc) were individually better in the group on the highest Mediterranean diet, higher percentage of women postmenopausal, BMI a bit lower (25 to 24.3). All of these differences were valid at a p <0.001

-- they assessed both incident cardiovascular events, as well as 40 biomarkers

Results:

-- incident cardiovascular events experienced by 1030 individuals (681 coronary and 339 stroke), per Mediterranean diet grouping:

    -- 428 (4.2%) in those on low Mediterranean diets

    -- 356 (3.8%) in middle range Mediterranean diets

    -- 246 (3.8%) in those on high Mediterranean diets

-- compared to the reference group of those on low Mediterranean diets:

    -- CVD risk reductions in those in the middle range decreased 23%, HR 0.77 (0.67-0.90)

    -- CVD risk reductions in those in the high group decreased 28%, HR 0.72 (0.61-0.86), p<0.001 for trend

-- in controlling for several risk factors, including age, randomized treatment assignment, energy intake, smoking, menopausal status, postmenopausal hormone use, physical activity, and parental history of MI before age 60 (their "basic model"):

    -- CVD risk reduction for both intermediate and high Mediterranean diets was a 15% decrease, but still with a significant trend, p=0.04

-- the largest mediators of CVD risk reduction for increasing Mediterranean diet intake:

    -- inflammatory biomarkers: 29.2%

    -- glucose metabolism/insulin resistance: 27.9%

    -- BMI: 27.3%

    -- blood pressure: 26.6%

    -- traditional lipids overall: 26.0%

    -- HDL: 24.0%

    -- VLDL: 20.8%

    -- lesser contributors included: LDL, branched-chain amino acids, apolipoproteins, other small-molecule metabolites (citrate, creatinine, homocysteine)

-- it should be noted that looking at the individual biomarker components themselves, and adjusting for both the basic model noted above as well as each of the other individual groupings of markers, there was no statistical significance for increasing Mediterranean diet consumption, though essentially all of these components were pretty dramatically skewed to benefit (e.g. confidence interval ranges of 0.74-1.03).  These tended to be more statistically significant in the medium Mediterranean diet group than the high one [likely because there were fewer events overall in the group with higher Mediterranean diets, the smallest group, which limits the ability to find statistical significance]

-- the overall association with Mediterranean diets was strongest for CAD vs stroke, though there was a similar pattern for risk reduction

Commentary:

-- several old and new studies have confirmed the clinical benefit of Mediterranean diets, even in non-Mediterranean countries. Some, such as the Lyon Diet Heart trial of 605 French men after 1^st MI who were randomized to a Mediterranean diet vs the old American Heart Association step 1 diet, found a 50 to 70% lower risk of recurrent CVD events with the Mediterranean diet (better than our current experience with statins). for another study, see http://gmodestmedblogs.blogspot.com/2018/06/mediterranean-diet-with-olive-oil-or.html 

-- this Women’s Health Study showed a few important things:

    -- it reinforced the clinical value of a high Mediterranean diet in the primary prevention of cardiovascular disease, with a decrease in clinical events on the order of 25% (similar to other studies)

    -- it reinforced the importance of several of the traditional risk factors including hypertension, lipids, and insulin resistance

    -- it added to the list several novel ones, including inflammatory markers (also supported in the JUPITER  trial, where rosuvastatin decreased cardiac events in those with high CRP levels, independent of their LDL levels, which were lowish at baseline). Other studies have also shown that inflammatory markers are decreased with the Mediterranean diet (eg, see mediterranean diet and dec inflamm markers nutr2015 in dropbox, or doi:10.3390/nu7064124 

-- another important concern reinforced by this trial: many of the dietary intervention trials are quite reductionist, trying to find that individual component of diet, or supplement/vitamin, associated with disease (i.e the magic bullet approach, typically encoded as a pill). By looking more globally at dietary intake, as with adherence to a Mediterranean diet, is not just more holistic but also reflects the complex interactions of the individual dietary components with each other. And we as a species evolved over eons to get adequate nutrition based on the composite of different groups of whole foods (not pills of purified ones)….

-- there are evident limitations to the generalizability of the above study: the diet was assessed through food frequency questionnaires/self reporting, these were US female healthcare professionals only, the baseline data were assessed at entry 20 years ago and they did not incorporate changes that might have taken place over the long time period of the study. It is hard in a study, even one this large, to tease out the relative role of individual risk factors separately from all of the others. And, as with any observational study, there may well have been unassessed but important risk factors.

-- It should be reinforced that a Mediterranean-type diet has multiple benefits, well beyond CAD:

    -- atrial fibrillation: see http://gmodestmedblogs.blogspot.com/2014/05/olive-oil-and-atrial-fibrillation.html 

    -- cancer risk: decreasing breast cancer, see http://gmodestmedblogs.blogspot.com/2015/11/breast-cancer-risk-and-mediterranean.html 

    -- diabetes risk: see http://gmodestmedblogs.blogspot.com/2014/01/mediterranean-diet-diabetes-prevention.html 

    -- cognitive effects: decreases brain atrophy with aging, see http://gmodestmedblogs.blogspot.com/2015/11/mediterranean-diet-and-brain-volume.html

    -- NAFLD: see http://gmodestmedblogs.blogspot.com/2017/10/mediterranean-diet-helps-nafld.html 

    -- knee osteoarthritis: see http://gmodestmedblogs.blogspot.com/2018/11/mediterranean-diet-decreases-knee-oa.html 

    -- longevity: see http://gmodestmedblogs.blogspot.com/2014/12/mediterranean-diet-and-longevity.html  and http://gmodestmedblogs.blogspot.com/2017/08/changing-diet-changes-lifespan_7.html

    --and, no doubt more....

So, this study adds to the very large aggregate data showing that increased adherence to the Mediterranean diet is important for preventing disease (as well as decreasing risk of recurrent cardiovascular disease, for example), that the relative benefit of this type of diet is at the same level of benefit as our medications (statins, aspirin, etc.), and that we clinicians should feel increasingly empowered to discuss diet as a very important part of our clinical interactions.  as they say, you are what you eat....

geoff

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