Heart diseases and cardiovascular diseases (CVDs) are the most important cause of death in industrialized and developing countries (1). The prevalence of CVDs is increasing leading to mortality and reduced quality of life from childhood to old age (2). The World Health Organization reported that about 17.3 million deaths in 2008 were due to CVDs (30% of all deaths) and it is estimated that by 2030, there will be about 23.6 million deaths due to heart diseases, especially stroke (3). Coronary artery disease (CAD) is the main cause of death and disability in the population of Iran and accounts for approximately 50% of deaths each year (4).

CAD is characterized by atherosclerosis in epicardial coronary arteries (5). The angiographic severity is important in the progression and prognosis of CAD, and gensini scoring is more reliable compared to other methods of grading its severity. In addition, gensini scoring provides a quantitative variable compared to other systems, which is more valid in statistical analyses (6, 7). Age, gender, and family history are unchangeable risk factors, and tobacco use, diabetes, lack of physical activity, unhealthy diet, and stress are modifiable CAD risk factors (5). Diet plays an important role in regulating chronic inflammation, lipid, and blood pressure dysregulation, and increasing the risk of CVDs (8–13). The dietary inflammatory index (DII) is a dietary index designed by South Carolina University researchers to measure the inflammatory potential of diet (14). In previous studies, the DII score obtained from the food frequency questionnaire (FFQ) was significantly related to inflammatory biomarkers so that higher DII scores (indicating a diet causing more inflammation) showed a direct relationship with interleukin-6 (IL-6), tumor necrosis factor receptor 2 alpha (TNFα-R2), and C-reactive protein (CRP) levels (15).

Eating healthy diets reduces the risk of developing CAD (16, 17). Also, lowest adherence to an anti-inflammatory diet and the risk of CVDs are associate (18, 19). However, it has not been confirmed in some studies and different findings have been reported in men and women (20, 21). No study has investigated the relationship between DII and severe CAD using the gensini score in IRAN; therefore, considering the high prevalence of CVD and related costs imposed on societies, it is of considerable importance to provide new strategies to prevent the disease and find effective treatments with fewer complications. The purpose of this study was to investigate the relationship between DII and severe CAD in adults. Accordingly, by understanding the dietary patterns of these patients, we can provide practical recommendations and take a step toward the health of society by promoting the correct dietary pattern.

In this cross-sectional study, 275 Iranian adults referring to Chamran and Asgaria hospitals (a government hospital and a private hospital) for angiography were studied, of whom 59.3% were men. The average age, weight, and BMI of the participants were 59.10 ± 8.57 years, 77.63 ± 11.17 kg, and 28.5 ± 4.06 kg/m², respectively. Also, 59.6% of people had severe CAD and the average DII was −0.50 ± 4.49. The general characteristics of the participants regarding DII tertiles are presented in Table 1. Those in the upper tertiles of the DII were older and more anticoagulant drug consumption, had higher average weight and higher economic status, and were found with less fatty liver and diabetes compared to the lower tertiles. There was no significant difference in the distribution of other variables among the tertiles of the DII. The food intake of the participants in the study is presented in Table 2. Those in the upper tertile of the dietary inflammatory index had less intake of nuts, whole grains, carbohydrates, thiamin, vitamin D, pepper and tea than the lower tertiles. Also, those in the upper tertile of the DII were found with higher intakes of energy, protein, fat, SFA, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), cholesterol, omega-3, omega-6, iron, zinc, vitamin B2, vitamin B6, vitamin B9, vitamin B12, vitamin C, vitamin E, vitamin A, beta carotene, onions, legumes, refined grains, red and processed meat, and vegetables compared to than the lower tertiles. No other significant difference in dietary intakes was observed among the tertiles of the dietary inflammatory index.

The raw and adjusted average severe CAD, lipid profile, and BP among the tertiles of DII are shown in Table 3. A significant difference was observed between the three levels of the DII in terms of the gensini score and the mean serum concentrations of q-CRP and total cholesterol, and this difference was also significant in the adjusted models. According to proximity tests, low adherence to the anti-inflammatory diet caused an increase in the gensini score (p < 0.001) and the mean concentrations of serum q-CRP (p < 0.001) and total cholesterol (p < 0.001). Also, those in higher tertiles of DII had higher mean systolic blood pressure than those in lower tertiles of DII (p = 0.04), which was not significant in the adjusted model. The crude and adjusted OR and 95% CI for severe CAD, high levels of lipid profile, high levels of q-CRP, and hypertension among the tertiles of DII are presented in Table 4. A direct and significant relationship was observed between the DII and severe CAD. People with the lowest adherence to anti-inflammatory diet had a 3.71 times higher chance of suffering from severe CAD than those with the highest adherence to anti-inflammatory (OR: 3.71; 95% CI: 1.97–6.98). This significance was also seen in the adjusted model, so that after adjusting the confounding variables, people with the lowest adherence to anti-inflammatory diet had a 6.09 times higher chance of suffering from severe CAD than those with the highest adherence to anti-inflammatory diet (OR: 6.09; 95% CI: 13.47–2.75). A direct and significant relationship was observed between the DII and increased q-CRP levels so that lower adherence to an anti-inflammatory diet increased the odds of q-CRP positivity by 2.11 times. However, this association disappeared after adjusting for confounding factors in the adjusted model (OR: 2.02; 95% CI: 0.86–4.73). There was a direct and significant relationship was found between lower adherence to an anti-inflammatory diet and hypercholesterolemia (OR of the third tertile compared to the first tertile: 2.73; 95% CI: 1.48–5.03), decreased HDL-cholesterol levels (OR of the tertile third compared to the first tertile: 3.77; 95% CI: 1.52–9.34) and hypertension (OR of the third tertile compared to the first tertile: 1.93; 95% CI: 3.49–1/06) in the raw model. After adjustment for the confounding factors, the relationship remained direct and significant. In the crude model, regarding the lower adherence to the anti-inflammatory diet, the chance of developing hypertriglyceridemia (OR: 2.02; 95% CI: 0.86–4-73) and LDL-C (OR: 2.02; 95% CI: 0.86–4.73) increased; however, this relationship was not statistically significant, and after adjusting for confounding factors, no significance was observed.

In the present study, a linear and direct relationship was observed between the DII and severe CAD. We also observed a significant difference between the DII tertiles in terms of gensini score. We found that a significant percentage of the participants were suffering from severe CAD (59.6%). Atherosclerosis is still the main cause of death with an increasing prevalence globally (34); thus, following anti-inflammatory regimens can positively affect the reduction of complications caused by blood clots.

Consistent with our study, other studies in the United States (35, 36), Australia (37), and Europe (38) showed that DII scores are positively associated with CAD risk. In a case–control study published in Jordan in 2019, a significant relationship was found between DII and the risk of CAD (18). In a prospective cohort study in Australia, the risk of CAD in men with a pro-inflammatory diet increased two times during the study (39). A randomized trial, PREDIMED, in Span showed that the risk of CAD in the fourth DII quartile increased by 73% compared to the first quartile (11). Also, in a case–control study conducted in northern Sweden, the risk of myocardial infarction in men with higher adherence to an inflammatory diet increased by 57% compared to people with low adherence (40). A meta-analysis, using data related to 14 eligible studies, examined the relationship between DII and the risk of CAD and its related mortality and it was found that the risk of CAD increased by 36% in people with higher adherence to the inflammatory diet (41). Another systematic review and meta-analysis conducted by Namazi et al. showed a positive and significant relationship between DII and the risk of CAD (42). In a cross-sectional study conducted in Iran, some components, such as nuts, showed an inverse and significant relationship with a decrease in the risk of the disease (21). However, our results are not consistent with some studies.

The contradictory results may be due to different food patterns, populations, sample sizes, and genetics. In the cross-sectional study conducted in Iran, no significant relationship was observed between red meat consumption and CAD. Patients with CAD reported more consumption of nuts and the use of fresh and cooked vegetables, dried fruits, animal oil cakes, fried potatoes, and some dairy products was correlated with CAD (20). Although several studies have been done on DII and its relationship with CAD, according to the researcher’s knowledge, no study has evaluated the relationship between DII and CAD severity using the gensini score in IRAN.

Several mechanisms have been proposed to explain the association between DII and vascular occlusion. Several theories have shown the consistent relationship between DII and the risk of developing CAD and its mortality; for example, the pro-inflammatory association of diet on increasing the level of cytokines, such as IL-1 and TNF-α, which causes the attraction and movement of inflammatory cells to the surface of the vascular endothelium (43) and induces the expression of cell adhesion molecules mediating leukocyte adhesion to the vascular endothelium (44).They also induce “messenger” cytokines, which increase the production of acute phase reactants, including CRP and serum amyloid A (SAA) through releasing into the systemic circulation (45). Inflammation in all stages of atherothrombosis is the main cause of about 80% of sudden cardiac deaths (SCD) (46). In previous studies, the DII score obtained from the FFQ was significantly associated with inflammatory biomarkers. Thus, higher DII scores (indicating a more inflammatory diet) have been directly related to IL-6, TNFα-R2, and CRP (15). IL-6 is the main pro-coagulant cytokine and can increase the concentration of fibrinogen, plasminogen activator inhibitor type 1 (47), and CRP, leading to an increase in pro-inflammatory and pro-coagulant responses (48). The basis of the relationship between CRP and atherosclerosis is the CRP’s potential to directly modulate the production of endothelium-derived vasoactive factors. Nitric oxide(NO) is the key factor in maintaining vascular tone and the central controller of cardiovascular homeostasis, which is derived from vascular endothelium (49). The reduced production or effect of NO through increased vascular contraction, leukocyte adhesion, platelet activation, oxidation, thrombosis, coagulation disorders, and vascular inflammation plays an essential role in the pathogenesis of the vascular atherosclerotic disease (50). Anti-inflammatory diet exert their effects on arterial blockage by reducing IL-6, TNFα-R2, and CRP levels (15). A number of studies have been shown that anti-inflammatory diet can modulate endothelium dependent vasodilation responses, endothelium-leukocyte interactions as well as balance between pro-and antithrombotic properties (51).

We also showed that lower adherence of an anti-inflammatory diet is related to an incremented risk of high blood pressure. The findings of the present study are confirmed by other studies indicating a positive relationship between the inflammatory potential of diet and hypertension (52, 53). Also, several prospective trials have associated increased inflammation with higher risks of hypertension (54). Inflammatory cytokines can strongly induce high blood pressure, which plays a role in regulating blood pressure due to the disruption of the renin-angiotensin system, vascular inflammation, and the reduction of NO production (55). The inflammation as well as the production of inflammatory cytokines activate the immune system and increase the expression of the angiotensinogen gene and angiotensin-converting enzyme (52), which ultimately causes the production of angiotensin 2, a strong constrictor, and increases blood pressure. On the other hand, inflammation and vascular damage can reduce the production of NO as a vasodilator, leading to high blood pressure (56).

Also, less following an anti-inflammatory diet was related to an increased risk of hypercholesterolemia and reduced HDL-C. A low-quality diet including excessive consumption of inflammatory food items increases lipogenesis (57, 58). A recently published prospective population-based study showed that a pro-inflammatory diet was associated with an increased risk of dyslipidemia (59). In a meta-analysis, higher levels of DII were associated with higher levels of TG and LDL-C in apparently healthy populations (60). The relationship between DII and increased TG and decreased HDL-C has also been reported (61). Therefore, the contradictory results may be due to different food patterns, populations, sample sizes, and genetics.

The present study had strengths and weaknesses. The severity of coronary artery disease was determined based on gensini’s score, and its validity has been confirmed. Nutritional intake was evaluated using valid questionnaires. In addition, the effects of several potential confounding factors were controlled in data analyses. However, some limitations should be considered in interpreting the findings. Due to the cross-sectional design of the study, we could not infer a causal relationship between the DII and CAD. More prospective studies should be conducted to confirm the causality of the associations. Although a validated FFQ was used to assess dietary intakes, recall bias may have influenced the findings. In addition, we did not have information about family history of CAD and 12 dietary items to calculate the DII score, which could affect the results.

This cross-sectional study showed a direct and linear relationship between the DII and the occurrence of severe CAD. Also, a significant difference was found between the DII tertiles in terms of gensini score. It is recommended people that in order to reduce the inflammatory potential of the diet, people should minimize the consumption of foods such as fast food, bread and pasta made with white flour, deep fried items such as french fries, fried chicken and donuts.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Ethics Committee of Isfahan University of Medical Sciences. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

ZD, MB, OS, AK, SS, and GA contributed in design, conception, data interpretation, data collection, approval of the final version of the manuscript, manuscript drafting, and agreed for all aspects of the work. All authors contributed to the article and approved the submitted version.