Introduction:
Whole diet evaluated using dietary pattern is associated with systemic inflammation and coronary heart disease (CHD). Systemic inflammation also contributes to CHD risk. Genetic factors explain variations in whole diet, systemic inflammation, and CHD. However, it is unknown whether systemic inflammation is a mechanism linking whole diet to the long-term mortality risk from coronary heart disease independent of genes.
Hypothesis:
Systemic inflammation measured as plasma interleukin-6 levels medicates the association between whole diet and long-term mortality risk from coronary heart disease independent of genes.
Methods:
From the National Heart, Lung, and Blood Institute Twin Study, we included 554 white, middle-aged, veteran male twins (105 monozygotic and 109 dizygotic twin pairs; 65 monozygotic and 61 dizygotic unpaired twins). The twins were not on antihypertensive medication and had diastolic blood pressure below 105 mmHg at baseline (1969-1973) and did not have suspected acute inflammation [plasma levels of interleukin-6 (IL-6) above 10 pg/mL or C-reactive protein above 30 mg/L)]. Usual dietary data at baseline were collected through nutritionist-administered dietary history interview. Your-Choice American Heart Diet (YCARD) score was devised to quantitatively evaluate whole diet. Plasma interleukin-6 and C-reactive protein levels were measured with ELISA. Data on vital status and death causes were collected through death certificates until Dec 31, 2010. A frailty survival model was used to estimate various associations: overall (equivalent to the association in the general population), within-pair (independent of genes and environment common to co-twins), and between-pair (indicating influence of the common factors). We controlled for total caloric intake and known CHD risk factors including body mass index and modified Framingham Risk Score.
Results:
There were 75 CHD deaths during a 41-year follow-up (median follow-up of 34 years). The adjusted overall association between YCARD score and the CHD mortality risk was negative [partial coefficient for a 10-unit increment in the YCARD score: βo (95% confidence interval (CI)): -0.13 (-0.24, -0.02); hazard ratio (95% CI): 0.88 (0.78, 0.98)]. The partial regression coefficient was -0.02 [95% CI (-0.23, 0.19)] for the within-pair effect of YCARD (βw) and -0.12 [95% CI (-0.26, 0)] for the between-pair effect of YCARD (βb) in relation to CHD mortality risk. Additional adjustment for IL-6 led to a 15.4% reduction in the βo, a 100% increment in the βw, and a 16.7% reduction in the βb.
Conclusions:
Systemic inflammation measured as interleukin-6 mediates the association between whole diet and long-term coronary heart mortality risk, which is largely through genetic and environmental factors shared between co-twins.
Interleukin-6 −174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS)