Despite the progresses in health care, cardiovascular disease (CVD) remains the main cause of death worldwide [1]. Recently cardiovascular mortality is increasing in developing countries, mostly because of the influence of Western lifestyle, such as smoking, lack of physical activity and dietary habits. In Iran, as a developing country, CVDs are considered as the most leading causes of mortality [2] and there is a rising trend in its prevalence [3]. CVD occurred as a result of numerous risk factors such as, diabetes, obesity, high blood pressure, dyslipidemia and smoking [4]. Furthermore, dietary factors and life style patterns are more important in development of CVD [5]. Several investigations described the role of diet and nutrients in the expansion of metabolic diseases [6,7]. High intake of cholesterol and saturated fatty acids are associated with CVD mortality [8]. Despite the expectation that the dairy products (as a main source of cholesterol and saturated fat) may lead to development of CVD and metabolic diseases, the results of different studies are inconsistent. Although several studies have shown the hypercholesterolaemic effect of diets rich in dairy products, [9,10] others couldn't find any association between milk consumption and CVD [11]. Moreover, some studies showed positive effects on metabolic parameters as a result of consumption of milk products. These studies suggest that the intake of dairy products, as a good source of essential nutrients and high quality protein, may reduce the risk of heart disease [12,13]. Cheese as a high saturated fat dairy product, may increase cholesterol concentration and can be associated with higher CVD risk [14,15]; contrarily, cheese is a good source of calcium (Ca) that might reduce heart disease by influencing plasma lipid profiles [16], reduce blood pressure [17,18], and adiposity [19,20]. It has been claimed that the intake of fermented products like cheese is negatively associated with cholesterol concentration [21]. Previous investigations indicated that cheese may not have any unfavorable effect on lipid profiles [22] and that cheese may even have a cholesterol lowering effect [23]. A recent study reported that the frequency of consumption of cheese was negatively associated with serum TG and positively associated with serum HDL cholesterol [24]. In contrast, some studies found non-significant association between cheese consumption and heart disease [25,26]. Another study reported that cheese intake is positively associated with myocardial infarction [27]. Overall, due to inconsistent results, the effect of cheese on CVD risk factors has remained uncertain [28]. Cheese has been one of the most important dairy products in Iranian diet, especially for breakfast [29]. Furthermore, the studies on cheese and CVD risks were done in the western and developed countries with different lifestyle, and according to our knowledge there is no study from developing countries, particularly the Middle East region including Iran. Therefore, current study aimed to investigate the association between cheese intake and cardiovascular risk factors among Iranian people.

Characteristics of study participants by frequency of cheese consumption per week are presented in Table 1. Individuals who consumed more cheese (7 ≤ times per week) were older, mostly female, and tended to have higher BMI, waist and waist to hip ratio with different education status in comparison with people with lower cheese intake (< 7 times per week) group. No significant difference was found in physical activity and smoking between two groups. Table 2 indicates the cardiovascular risk factors of study participants by the frequency of cheese consumption. Higher consumption of cheese was associated with higher CRP, apolipoprotein A and HDL level but not with other cardiovascular risk factors including FBS, total cholesterol, LDL-C, TG and Apo B. Dietary intake of participants by frequency of cheese consumption are shown in Table 3. Higher consumption of cheese was positively associated with consumption of liquid and solid oil, grain, pulses, fruit, vegetable, meat and dairy products and negatively associated with Global Dietary Index. Crude and multivariate-adjusted odds ratio and 95% CI of cardiovascular risk factors in different groups of cheese intake are presented in Table 4. In crude model there was no difference between two groups but after adjustment for age and sex, low HDL level was negatively associated with cheese consumption (OR:0.89; 96% CI: 0.80-0.98). After control for other potential confounders such as dietary intakes and physical activity the association did not change. Further adjustment for BMI showed strong negative association between cheese intake with metabolic syndrome (OR:0.81; 96% CI: 0.71-0.94), low HDL level (OR:0.87; 96% CI: 0.79-0.96), and dyslipidemia (OR:0.88; 96%vCI: 0.79-0.98).

In the present cross-sectional study as part of Isfahan Healthy Heart Program (IHHP), higher consumption of cheese was associated with lower cardiovascular and metabolic risk factors, which shows the beneficial effect of cheese intake. These results are apparently in contrast with previous knowledge about blood lipids and dietary fat consumption as cheese considered as a main source of saturated fat among dairy products. It has been reported that milk and dairy products consumption were positively correlated with total cholesterol, LDL-C and HDL-C levels [9]. In contrary, the consumption of milk and its products has been demonstrated to be negatively associated with the prevalence of metabolic syndrome [32]. These results are reported from various populations that consume different kinds of milk products, and this difference may be one possible reason for this inconsistency. For example, high consumption of milk in Scandinavian countries led to high mortality of heart disease whereas, high consumption of cheese in France may be one of the reasons of low heart disease mortality [33].

It is supposed that the effect of fat intake from cheese on serum lipids might be different from what expected from fat content. In a previous study a positive relationship was found between the intake of milk and heart disease mortality, although cheese consumption was negatively but not significantly correlated [25]. Another study showed a positive association between dairy fat intake and coronary heart diseases but the study recommended that cheese could be an exception [34]. Other studies also reported that individuals in higher category of cheese consumption were not at higher risk of myocardial infarction [28], hypertriglyceridemia [33] or high LDL-C level [35] than people consuming lower amount of cheese. It has been reported that cheese consumption could even reduce LDL-C in comparison with equal fat from butter [36].

Our finding that higher consumption of cheese can be inversely associated with cardiovascular risk factors including metabolic syndrome, low HDL-C level and hyperlipidemia is in accordance with other earlier investigations on cheese consumption, which showed positive association between the intake of cheese and HDL-C level [24], and a negative association with total cholesterol levels [37] and metabolic syndrome [38,39]. Nevertheless, a prospective study found a positive association between cheese intake and cholesterol level, as well as IHD mortality [40]. Other studies reported a positive association between cheeses consumption and metabolic syndrome [41], cardiovascular risk factors [14] and myocardial infarction [27]. Different results among various studies might be depended on different population samples, lifestyles and study design [39].

A possible mechanism for beneficial effect of cheese consumption could be the effect of the high content of calcium in cheese. Previous studies showed that dietary calcium with fat generate calcium soup and increase the excretion of lipid in feces [42] and significantly reduce serum cholesterol and triglyceride levels [43]. The effect of fermented dairy products on cholesterol concentration could be another mechanism for cheese effect. It has been suggested that the bacteria existed in large intestine convert unabsorbed carbohydrates to short-chain fatty acids, which could modify cholesterol synthesis in the liver. Also, these bacteria could bind bile acids to cholesterol and increase its excretion and reduce bile acid recycling [21]. Furthermore, high protein content of cheese, hypothesized as another possible mechanism for its effect on cholesterol [36].

Several limitations are considered in the current study. First, this study was designed as a cross-sectional study that makes decision on causality impossible. Second, to assess dietary intake we used qualitative FFQ that may lead to misclassification and underestimation and just give a crude estimate of the cheese intake, although it has been claimed that single FFQ ranks participants on total intake [44]. Third, there might be some residual confounding affecting the association between cheese consumption and cardiovascular risk factors, such as other lifestyle, dietary factors and dietary supplementation that were not controlled in our analysis. Finally we didn't know about the fat content of consumed cheese. The fat content of cheese is an important factor influencing the result of different studies.

In conclusion, we found an inverse association between frequency of cheese intake and cardiovascular risk factors; however, further prospective studies are required to confirm the present results and to illustrate the probable mechanism.