Table 5. Validity analyses comparing the observed relative risks for CHD based on evidence from prospective observational studies and randomized trials of dietary patterns versus the estimated relative risks for CHD based on the present analysis of individual dietary components.

	Observed Relative Risk for CHD 1	Estimated Relative Risk for CHD 2
Prospective cohort studies evaluating associations of overall dietary patterns with incident CHD 3
Health Professionals Study—Prudent diet (average of all quintiles, with lowest quintile as the reference) [40]	0.82	0.78
Health Professionals Study—Western diet (average of all quintiles, with lowest quintile as the reference) [40]	1.29	1.17
Nurse’s Health Study—Prudent diet (average of all quintiles, with lowest quintile as the reference) [41]	0.82	0.80
Nurse’s Health Study—Western diet (average of all quintiles, with lowest quintile as the reference) [41]	1.20	1.10
Nurse’s Health Study—Mediterranean diet (average of all quintiles, with lowest quintile as the reference) [42]	0.84	0.81
EPIC-Greek (per 2 units diet score increase) [43]	0.78	0.90
SUN-Spain (per 2 units diet score increase) [44]	0.74	0.75
Randomized controlled feeding trials evaluating effects of overall dietary patterns on BP and LDL-C 4
Fruits, serving/d (100 g/d)	0.93	0.94
Vegetables, serving/d (100 g/d)	0.93	0.95
Nuts and seeds, serving/wk (1 oz [28.35 g]/wk)	0.93	0.93
Whole grains, serving/d (50 g/d)	0.88	0.97
Fish, serving/d (100 g/d)	0.87	0.66
Red meat, serving/d (100 g/d)	1.17	1.17
Dietary fiber, 20 g/d	0.77	0.76
Randomized clinical trial evaluating effects of an overall dietary pattern on incident CHD [53, 99] 5
Mediterranean diet + extra-virgin olive oil vs. placebo	0.80	0.77
Mediterranean diet + mixed nuts vs. placebo	0.74	0.62
Combined groups	0.77	0.69

¹ Values are the observed relative risks (RRs) in these long-term prospective observational studies or randomized trials of dietary patterns.

² Values are the estimated RRs based on the reported differences in intakes of individual dietary factors across each category of the diet pattern study and our estimated quantitative effects for these individual dietary factors (Table 2), assuming a multiplicative relation of proportional effects of individual components. Not all dietary factors in Table 2 were included due to insufficient reporting of differences in these components across studies of dietary patterns. We focused on foods and excluded overlapping nutrients (e.g., we included whole grains, fruits, and vegetables; and excluded fiber, glycemic load). We also assumed no benefits from differences in other dietary factors (e.g., coffee) in the dietary pattern for which we had not determined a causal etiologic effect.

³ Because the observed relative risks in most of these cohorts were based on serial dietary measures with time-varying updating, the predicted relative risks for each dietary factor were adjusted for comparability for regression dilution bias due to the observed changes over time of each dietary factor in these cohorts. See Table D in S1 File for more details.

⁴ For randomized controlled feeding trials of dietary patterns and cardiovascular risk factors, we performed inverse-variance-weighted meta-regression across all of the treatment arms of three large, well-established dietary pattern trials [45–47] to estimate the independent effects of five different dietary components, when consumed as part of an overall dietary pattern, on systolic blood pressure (SBP) and LDL-cholesterol (LDL-C). We evaluated achieved dietary changes in fruits, vegetables, nuts, whole grains, and fish simultaneously as independent variables in the meta-regression, with changes in SBP or LDL-C as the dependent variable. For each dietary factor, we then calculated how the identified change in SBP and LDL-C from the meta-regression would alter cardiovascular risk, based on the established relationship between SBP and LDL-C and clinical events [48–52], assuming independent, multiplicative effects of SBP and LDL-C on risk. These observed effects, calculated based only on how each dietary factor altered SBP and LDL-C in randomized controlled feeding trials of diet patterns, were then compared to our estimated etiologic effect on coronary heart disease (CHD) events for that dietary factor (Table 2). See Table E in S1 File for more details.

⁵ We compared the observed vs. predicted risk in a large randomized clinical trial evaluating the effects of two overall dietary patterns on incidence of cardiovascular events [53]. A similar analysis was previously reported using 2010 NutriCode RR’s [99]; the values here are based on the updated RR’s in the current investigation (Table 2). The predicted risk reductions were calculated by combining the observed differences in individual dietary components achieved in the trial with our estimated quantitative effects, assuming multiplicative effects of each individual component. Because we had not identified sufficient studies to quantify etiologic effects of extra-virgin olive oil, to enable comparison we imputed potential effects of extra-virgin olive oil from our estimated relative risk for polyunsaturated vegetable fats. See Table F in S1 File for more details.