Table 5.
Blood biomarkers and established cardiovascular disease risk factors as mediators of association of Food Standards Agency nutrient profiling system (FSAm-NPS) dietary index or ultra-processed food intake (weight ratio) with all cause and cardiovascular disease mortality among 22 895 participants from Moli-sani Study cohort (2005-10)
| Risk factors | FSAm-NPS dietary index | Ultra-processed food | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| All cause mortality | Cardiovascular disease mortality | All cause mortality | Cardiovascular disease mortality | ||||||||
| Proportion mediated (95% CI)* | P value | Proportion mediated (95% CI)* | P value | Proportion mediated (95% CI)* | P value | Proportion mediated (95% CI)* | P value | ||||
| Multivariable model + markers of glucose metabolism† | 8.9 (4.0 to 18.5) | <0.001 | - | - | 5.8 (1.9 to 16.9) | 0.02 | - | - | |||
| Multivariable model + markers of renal function‡ | - | - | - | - | 26.0 (12.1 to 47.4) | <0.001 | 21.8 (8.7 to 44.8) | <0.001 | |||
| Multivariable model + blood cholesterol | 4.2 (1.4 to 12.0) | 0.02 | - | - | 8.5 (3.8 to 17.9) | <0.001 | - | - | |||
| Multivariable model + markers of inflammation§ | 3.5 (0.3 to 28.8) | 0.2 | 4.5 (0.7 to 22.7) | 0.1 | 10.0 (3.6 to 25.1) | 0.007 | 10.6 (3.3 to 29.5) | 0.01 | |||
| Multivariable model + systolic and diastolic BP + heart rate | - | - | - | - | 2.1 (0.0 to 58.8) | 0.3 | NM | NM | |||
| Multivariable model + diastolic BP | NM | NM | NM | NM | - | - | - | - | |||
| Multivariable model + serum vitamin D | 2.8 (0.4 to 17.8) | 0.1 | 1.2 (0.1 to 15.7) | 0.2 | - | - | - | - | |||
| Multivariable model + all explanatory factors | 18.6 (7.6 to 38.7) | <0.001 | 3.7 (0.3 to 32.0) | 0.2 | 32.7 (13.9 to 59.3) | <0.001 | 17.4 (5.0 to 45.6) | 0.02 | |||
BP=blood pressure; CI=confidence interval; NM=not mediating.
Proportion of effect explained by intermediate variables with 95% CI and relevant P value as produced by %MEDIATE macro in SAS are reported for each potential mediator, in multivariable adjusted Cox proportional hazards models controlled for sex, age (continuous), energy intake (continuous), educational level (categorical), housing tenure (categorical), smoking (categorical), body mass index (continuous), leisure time physical activity (continuous), history of cancer (no/yes), history of cardiovascular disease (no/yes), diabetes (no/yes), hypertension (no/yes), hyperlipidaemia (no/yes), and residence (categorical). Proportion refers to quarter 4 versus quarter 1 of each dietary index. Mediation analyses were generated using first imputed dataset. Other imputed datasets were similar and thus omitted.
Markers of glucose metabolism include insulin and C-peptide serum concentrations. For analyses of ultra-processed food intake with all cause mortality, blood glucose, insulin, and C-peptide serum concentrations were considered.
Markers of renal function include serum concentrations of cystatin-C and creatinine.
Markers of inflammation include C reactive protein, white blood cell count, and granulocyte-to-lymphocyte ratio.