Mediterranean diet with olive oil or nuts decrease CAD
Because of some flaws in its original report, there was a retraction and re-analysis of the PREDIMED trial published first in 2013, where Spanish patients at high cardiovascular risk were randomized to 2 different Mediterranean diets vs control diet, still finding a 30% decrease in cardiac events with the Mediterranean diet (see cad prevention medit diet EVOO nejm2018 in dropbox, or DOI: 10.1056/NEJMoa1800389).
Details:
--Multicenter Spanish trial with 7447 people aged 55-80 for men and 60-80 for women at high cardiovascular risk: diabetes type 2, or at least one of: smoking (>1 cigarette/d in last month), high LDL (≥ 160 mg/dl), low HDL (<40 mg/dl), hypertension (SBP ≥140 or DBP ≥90, or on meds), overweight/obesity (BMI ≥25), or family history of premature CAD (definite MI or sudden death <55yo in father or 1st degree male relative, or <65 in mother or 1st degree female relative) but no evident cardiovascular disease; enrolled in one of 3 diets, without calorie restriction or promotion of physical activity:
-- Mediterranean diet with extra-virgin olive oil (EVOO), patients given 1 quart/week: recommendation to have >= 4 tbsp/day
-- Mediterranean diet with mixed nuts, patients given 30 g mixed nuts/day (15 g walnuts, 7.5 g hazelnuts, 7.5 g almonds): recommendation to eat >=3 servings/week
-- control diet (advice to decrease dietary fat, but also discouraged olive oil and nuts)
--57% women, 67 yo, 97% white, 61% never-smoker/24% former-smoker/14% current smoker, BMI 30, hypertension 82%, diabetes 48%, dyslipidemia 72%, fam hxpremature CAD 22%, meds: ACE 50%/diuretics 21%/other bp meds 30%/statins 40%/insulin 5%/oral hypoglycemic 30%/antiplatelet 20%
--they assessed physical activity and a validated food-frequency questionnaire annually
--and on a random group, they assessed plasma alpha-linolenic acid levels to confirm adherence to the mixed nuts and urinary hydroxytyrosol levels to confirm adherence to EVOO
--the reason this trial was re-evaluated after the 2013 publication was because of subsequently identified protocol deviations (eg enrollment of household members without randomization, assignment to a treatment group without randomization in 1 of 11 sites, inconsistent randomization). Analysis was redone excluding these deviations
--the study was stopped early after a prespecified interim analysis, after a median of 4.8 yrs (2.8-5.8)
Results:
--those on the Mediterranean diets increased their weekly servings of fish by 0.3 servings, legumes by 0.4 servings, vs the control groups; and, the above biomarkers found good adherence to the 2 Mediterranean diet assignments, and dietary recall data suggested an increase in EVOO in that group by 32 g/d and nuts by 50 g/d
--primary endpoint in 288 people:
--Mediterranean diet with EVOO: 96 events, 8.1/1000 person-yrs (5-year absolute risk of 3.6%)
--Mediterranean diet with mixed nuts: 83 events, 8.0/1000 person-yrs (5-year absolute risk of 4.0%)
--control diet: 109 events, 11.2/1000 person-yrs (5-year absolute risk of 5.7%)
--intention-to-treat analysis for primary endpoint, adjusting for baseline characteristics and propensity score (a statistical method to equalize groups with disparate comorbidities, etc, after randomization), vs control diet:
--Mediterranean diet with EVOO: 31% decrease, HR 0.69 (0.53-0.91)
--Mediterranean diet with mixed nuts: 28% decrease, HR 0.72 (0.54-0.95)
--differences between the Mediterranean diet groups and control were more impressive as adherence to the diets increased: the per-protocol, adherence-adjusted HR for Mediterranean diet vs control was 0.42 (0.24-0.63), ie a 58% decrease
--results were similar to the 2013 report even after omitting the protocol deviators, including in all of the sensitivity analyses
Commentary:
--this redone study adds to the small RCT literature showing that dietary interventions can be profound in decreasing the risk of cardiovascular events (it turns out that drug companies have not much interest in funding these types of studies).
--The Lyon Diet Heart Study was an RCT for secondary prevention (patients who had previous MI and are therefore at high risk of another one), finding that those on a Mediterranean diet (vs “prudent” Western diet, as determined by their attending physicians, though the focus then was on low saturated fat diets) had a 72% decrease in cardiac death or nonfatal MI, and a 48% decrease in the combination of hard and soft cardiac endpoints after 4 years, with significant differences noted within the first 6 months of the diet (see cad Lyon diet heart study circ1999 in dropbox, or de Lorgeril M. Circ. 1999; 99:779)
--so, though limited studies, these primary and secondary prevention studies find that the benefit of a Mediterranean diet happens quickly (within months) and seems to be at least the same magnitude as using statins
--AND, these studies were in countries which already had a baseline diet which was Mediterranean-like (France and Spain). AND, the actual average change in consumption in the Mediterranean diet groups was really not so much over baseline
--this PREDIMED study translates into a decrease of 3 major cardiovascular events per 1000 person-yrs by eating a Mediterranean diet
--the patients in the control group did have less exposure to the researchers: during the first 3 years of the study, they got a leaflet every year explaining the low-fat diet. Then, realizing this was a big difference between the groups, the researchers had sessions with the control group at the same intensity as those on the Mediterranean diets. Interestingly, a separate analysis of patients recruited before and after this equalization of session intensity showed a 23% risk reduction with Mediterranean diet before and a 51% after
--the Mediterranean diet has been shown to decrease the metabolic syndrome, has anti-inflammatory effects, and improves endothelial function; all of which may explain some of the clinical benefit
So, i am bringing up this study again partly because there are so few RCTs done on diet either as primary or secondary prevention for heart disease, and largely because the current medical ethic is to jump for meds. the 2013 AHA guidelines barely mentioned diets (there certainly was no call for moderate- or high-intensity diets, depending on the cardiac risk score...). that is not to say that meds aren't good (and i do use statins lots, both in primary and secondary prevention). But diet, exercise, maintaining a good weight, having or developing social supports, decreasing stress.... is so important for good phyisical and mental health (well beyond the heart) that i think such a compelling study as the PREDIMED one should help reinforce to us and to our patients the key role of a healthy lifestyle....
For other blogs on the effects of the PREDIMED diet:
--see http://gmodestmedblogs.blogspot.com/2014/01/mediterranean-diet-and-primary.html for the original assessment of this trial on CAD prevention
--see http://gmodestmedblogs.blogspot.com/2014/05/olive-oil-and-atrial-fibrillation.html finding decreased atrial fibrillation with Mediterranean diet
--see http://gmodestmedblogs.blogspot.com/2014/01/mediterranean-diet-diabetes-prevention.html / for decrease in diabetes
--see http://gmodestmedblogs.blogspot.com/2015/11/breast-cancer-risk-and-mediterranean.html for decrease in breast cancer (with the EVOO diet)
--see http://gmodestmedblogs.blogspot.com/2015/11/mediterranean-diet-and-brain-volume.html for improved cognition, along with other Mediterranean diet studies showing decreased loss of MRI-documented total brain volume, with higher gray and white matter
Details:
--Multicenter Spanish trial with 7447 people aged 55-80 for men and 60-80 for women at high cardiovascular risk: diabetes type 2, or at least one of: smoking (>1 cigarette/d in last month), high LDL (≥ 160 mg/dl), low HDL (<40 mg/dl), hypertension (SBP ≥140 or DBP ≥90, or on meds), overweight/obesity (BMI ≥25), or family history of premature CAD (definite MI or sudden death <55yo in father or 1st degree male relative, or <65 in mother or 1st degree female relative) but no evident cardiovascular disease; enrolled in one of 3 diets, without calorie restriction or promotion of physical activity:
-- Mediterranean diet with extra-virgin olive oil (EVOO), patients given 1 quart/week: recommendation to have >= 4 tbsp/day
-- Mediterranean diet with mixed nuts, patients given 30 g mixed nuts/day (15 g walnuts, 7.5 g hazelnuts, 7.5 g almonds): recommendation to eat >=3 servings/week
-- control diet (advice to decrease dietary fat, but also discouraged olive oil and nuts)
--57% women, 67 yo, 97% white, 61% never-smoker/24% former-smoker/14% current smoker, BMI 30, hypertension 82%, diabetes 48%, dyslipidemia 72%, fam hxpremature CAD 22%, meds: ACE 50%/diuretics 21%/other bp meds 30%/statins 40%/insulin 5%/oral hypoglycemic 30%/antiplatelet 20%
--they assessed physical activity and a validated food-frequency questionnaire annually
--and on a random group, they assessed plasma alpha-linolenic acid levels to confirm adherence to the mixed nuts and urinary hydroxytyrosol levels to confirm adherence to EVOO
--the reason this trial was re-evaluated after the 2013 publication was because of subsequently identified protocol deviations (eg enrollment of household members without randomization, assignment to a treatment group without randomization in 1 of 11 sites, inconsistent randomization). Analysis was redone excluding these deviations
--the study was stopped early after a prespecified interim analysis, after a median of 4.8 yrs (2.8-5.8)
Results:
--those on the Mediterranean diets increased their weekly servings of fish by 0.3 servings, legumes by 0.4 servings, vs the control groups; and, the above biomarkers found good adherence to the 2 Mediterranean diet assignments, and dietary recall data suggested an increase in EVOO in that group by 32 g/d and nuts by 50 g/d
--primary endpoint in 288 people:
--Mediterranean diet with EVOO: 96 events, 8.1/1000 person-yrs (5-year absolute risk of 3.6%)
--Mediterranean diet with mixed nuts: 83 events, 8.0/1000 person-yrs (5-year absolute risk of 4.0%)
--control diet: 109 events, 11.2/1000 person-yrs (5-year absolute risk of 5.7%)
--intention-to-treat analysis for primary endpoint, adjusting for baseline characteristics and propensity score (a statistical method to equalize groups with disparate comorbidities, etc, after randomization), vs control diet:
--Mediterranean diet with EVOO: 31% decrease, HR 0.69 (0.53-0.91)
--Mediterranean diet with mixed nuts: 28% decrease, HR 0.72 (0.54-0.95)
--differences between the Mediterranean diet groups and control were more impressive as adherence to the diets increased: the per-protocol, adherence-adjusted HR for Mediterranean diet vs control was 0.42 (0.24-0.63), ie a 58% decrease
--results were similar to the 2013 report even after omitting the protocol deviators, including in all of the sensitivity analyses
--this redone study adds to the small RCT literature showing that dietary interventions can be profound in decreasing the risk of cardiovascular events (it turns out that drug companies have not much interest in funding these types of studies).
--The Lyon Diet Heart Study was an RCT for secondary prevention (patients who had previous MI and are therefore at high risk of another one), finding that those on a Mediterranean diet (vs “prudent” Western diet, as determined by their attending physicians, though the focus then was on low saturated fat diets) had a 72% decrease in cardiac death or nonfatal MI, and a 48% decrease in the combination of hard and soft cardiac endpoints after 4 years, with significant differences noted within the first 6 months of the diet (see cad Lyon diet heart study circ1999 in dropbox, or de Lorgeril M. Circ. 1999; 99:779)
--so, though limited studies, these primary and secondary prevention studies find that the benefit of a Mediterranean diet happens quickly (within months) and seems to be at least the same magnitude as using statins
--AND, these studies were in countries which already had a baseline diet which was Mediterranean-like (France and Spain). AND, the actual average change in consumption in the Mediterranean diet groups was really not so much over baseline
--this PREDIMED study translates into a decrease of 3 major cardiovascular events per 1000 person-yrs by eating a Mediterranean diet
--the patients in the control group did have less exposure to the researchers: during the first 3 years of the study, they got a leaflet every year explaining the low-fat diet. Then, realizing this was a big difference between the groups, the researchers had sessions with the control group at the same intensity as those on the Mediterranean diets. Interestingly, a separate analysis of patients recruited before and after this equalization of session intensity showed a 23% risk reduction with Mediterranean diet before and a 51% after
--the Mediterranean diet has been shown to decrease the metabolic syndrome, has anti-inflammatory effects, and improves endothelial function; all of which may explain some of the clinical benefit
So, i am bringing up this study again partly because there are so few RCTs done on diet either as primary or secondary prevention for heart disease, and largely because the current medical ethic is to jump for meds. the 2013 AHA guidelines barely mentioned diets (there certainly was no call for moderate- or high-intensity diets, depending on the cardiac risk score...). that is not to say that meds aren't good (and i do use statins lots, both in primary and secondary prevention). But diet, exercise, maintaining a good weight, having or developing social supports, decreasing stress.... is so important for good phyisical and mental health (well beyond the heart) that i think such a compelling study as the PREDIMED one should help reinforce to us and to our patients the key role of a healthy lifestyle....
For other blogs on the effects of the PREDIMED diet:
--see http://gmodestmedblogs.blogspot.com/2014/01/mediterranean-diet-and-primary.html for the original assessment of this trial on CAD prevention
--see http://gmodestmedblogs.blogspot.com/2014/05/olive-oil-and-atrial-fibrillation.html finding decreased atrial fibrillation with Mediterranean diet
--see http://gmodestmedblogs.blogspot.com/2014/01/mediterranean-diet-diabetes-prevention.html / for decrease in diabetes
--see http://gmodestmedblogs.blogspot.com/2015/11/breast-cancer-risk-and-mediterranean.html for decrease in breast cancer (with the EVOO diet)
--see http://gmodestmedblogs.blogspot.com/2015/11/mediterranean-diet-and-brain-volume.html for improved cognition, along with other Mediterranean diet studies showing decreased loss of MRI-documented total brain volume, with higher gray and white matter
geoff
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