Noushin Mohammadifard - Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
Fahimeh Haghighatdoost - Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
Niloofar Ghaderian - Hypertension Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences,Isfahan, Iran
Marjan Mansourian - Epidemiology and Biostatistics Department, Health School, Isfahan University of Medical Sciences,Isfahan, Iran

Background and Aim: Nuts are one of the richest sources of unsaturated fatty acids, plant proteins, antioxidant vitamins, minerals and plant sterols, which have cardioprotective effects. Evidences in this context mainly came from Mediterranean and Western populations, and there is no prospective observational report from Middle-Eastern countries. Due to geographic variability in cardiovascular morbidity, mortality and its risk factors, we aimed to investigate the association of nut consumption with cardiovascular events, cardiometabolic risk factors, cardiovascular mortality and all-cause deaths among Iranian population. Methods: This population-based prospective cohort study was conducted among 4834 randomly selected participants without history of cardiovascular disease (CVD) aged ≥35 years in urban and rural areas of central Iran (Isfahan, Arak and Najafabad). The subjects were followed for 12 years (2001-2013) within the framework of the Isfahan Cohort Study (ICS). Participants or their next of kin were interviewed biannually looking for possible occurrence of events. Cardiovascular events was defined as fatal or non-fatal myocardial infarction (MI), sudden cardiac death and fatal or non-fatal stroke. Total MI and sudden cardiac death defined as coronary heart disease (CHD). We assessed nuts consumption (walnuts, almonds, pistachios and hazelnuts) using a validated food frequency questionnaire. To deterimine the cardiometabolic risk factors including hypertension, dyslipidemia, diabetes mellitus and obesity, we measured blood pressure, fasting serum lipids, anthropometric measurements and blood sugars in three phases of the study among 1387 baseline participant, those who had complete information and also attended in both 2007 and 2013 repeated measurements. Cox proportional hazards models were used to examine the association between nut consumption and cardiovascular events. Mixed effect Logistic and Cumulative Logistic regressions were applied to evaluate the longitudinal associations between nut consumption and cardiometabolic risk factors. During the median follow-up of 144 months and 55017 person-years, we found a total number of 156 MI, 245 CHD, 157 stroke, 751 CVD, 179 CVD mortality and 458 all-cause death. Multivariable-adjusted hazard ratios (HR) for MI, CHD, stroke, CVD incidents, all-cause mortality and CVD mortality across quartiles of nut intake showed, in crude model, participants who ate more nuts had a lower risk of MI [HR (95% confidence interval (CI)): 0.5 (0.31-0.81); P for trend = 0.002], CHD (HR (95% CI): 0.46 (0.31-0.68); P for trend <0.001], stroke [HR (95% CI): 0.49 (0.31-0.77); P for trend <0.001] CVD [HR (95% CI): 0.57 (0.47-0.70); P for trend <0.001], all-cause mortality [HR (95% CI): 0.45 (0.33-0.61); P for trend <0.001] and CVD mortality [HR (95% CI): 0.24 (0.13-0.42); P for trend <0.001]. After adjustment for age and sex, those in highest nut quartiles were significantly less likely to have CHD, CVD and CVD mortality. In the other two adjusted models, including fully adjusted model, the association was diluted and no significant relationship was found between nut intake and MI, CHD, stroke, CVD incidents, all-cause mortality and CVD mortality. A greater intake of nuts was associated with lower occurrence of hypercholesterolemia [OR (95% CI): 0.76 (0.60-0.97); P=0.025], hypertriglyceridemia [OR (95% CI): 0.74 (0.58-0.93); P=0.011] and obesity [OR (95% CI): 0.79 0.50-0.98); P=0.033], but increased risk of diabetes [OR (95% CI): 1.85 (1.27-2.68); P=0.001]. However, after adjusting for various potential confounders, the associations remained significant only for obesity [OR (95% CI): 0.67 (0.48-0.94); P=0.018] and diabetes mellitus [OR (95% CI): 2.23 (1.37-3.64); P=0.001] occurrence. Conclusion: We concluded an inverse association between nut intake and lower risk of CVD events through unadjusted model, however it was disappeared after full adjustment for potential confounders. Nut consumption was associated with a decreased risk of obesity, but an increased risk of type 2 diabetes mellitus occurrence after controlling for potential confounders. Studies with long duration of follow-up considering the types of nuts based on their preparation methods (raw or roasted and salted) or their nature (walnut, pistachio, etc.,) might provide a better level of evidence to establish which kinds of nuts specifically, and to what extent, are responsible for higher influential effects of nuts on the risk of CVD and its risk factors.

Nuts; cardiovascular disease; dyslipidemia; diabetes mellitus; obesity; hypertension