In the current study, the association of several risk factors including socio-demographic, lifestyle, psychological, anthropometric factors, and underlying diseases with CVD risk was evaluated in a large cohort-design study. We observed significant direct correlations of age, BMI, WC, WHtR, FH of CVD and DM and also negative correlation of PAL with the risk of CVD events among both genders. WHR increased the risk of CVD in males, while education played a protective role against CVD among females. In addition, higher CVD incidence was in a relationship with some other underlying disorders including HTN, MS, depression and anxiety in females. There are various reports about the different risk factors and their effects on CVD incidence (10). Cardiovascular risk factors can be categorized as unmodifiable, modifiable, and behavioral risk factors (35). In the present study, we defined the correlations between some risk factors and CVD incidence in a 6 years follow-up cohort study. All of these impressive risk factors are categorized as modifiable risk factors, except for age and positive FH, and should be concerned in the policy of the governments (35). As well, preventive medicine should be at attention for people with positive FH and ageing process (35).
This study has shown that WHR is the best anthropometric measure as far better as BMI, WC and WHtR to use in clinic to recognizing subjects with risk factors for CVD; also, it was the most effective risk factor for CVD by the greatest HR. Filippatos et al. have shown that anthropometric indices (BMI, WHR, WC, and WHR, WHtR) were autonomously associated with the 10-year CVD risk (36). Individuals with different ethnicities have different body characteristics (37) and it’s so crucial to clarify easy and useful anthropometric measurements for screening and pre-screening of subjects particularly those with higher metabolic risk in different populations. As a result, Ethnicity should be integrated into CVD assessment and this area (Ethnic Specific) in the case of CVD prevention and treatment strategies need further studies and should be more developed (38). Few studies have investigated the relationships between anthropometric measurements with common cardiovascular risk factors in Iran (39–41) and we want to determine the best anthropometric measurements that predict CVD in a longitudinal study. Although BMI analysis is simple and convenient to monitor, many clinical and metabolic studies have revealed that, when obesity is defined just based on BMI alone, it considers the heterogeneous condition, which patients with a close BMI may have distinct metabolic and CVD features (42, 43). Esmaillzadeh et al. in a cross-sectional survey has demonstrated that WHR is a better predictor for CV risk factors rather than BMI, WHtR and WC in adult men of Tehran (a city of Iran) (41). In a cross-sectional study, they have represented that WC is the best screening measure for CVD risk factors, in the adult population of Tehranian women (40). Yan et al. have supported the WHR is useful for evaluating atherosclerotic burden in obesity screening and clinical researches. They showed that the elevated CVD risk associated with abdominal obesity may be mediated in part by the raised anatomic extent of atherosclerotic vascular disorder (44). In a Multi-Ethnic Study in 52 countries, the data have demonstrated that by redefinition of overweight and obesity criteria’s based on WHR instead of BMI, the number of people in the worldwide who categorized at risk of heart attack will be increased threefold (45) and it was a significant predictor of myocardial infarction among both genders without an enlarged WC in adjusted analyses (46). Sehested et al. illustrated that in various forms of obesity and overweight measures, WHR was the only meaningful predictor of the incident of CVD, and the relationship between WHR and risk of CVD was refereed by noted CVD risk factors (47). Simpson et al. in a cohort study have revealed that WHR was positively related to all main cause mortality for both genders (48). However, WC, not WHR in some communities (49, 50), and WHtR in others (51, 52) have been suggested as a better screening tool for CVD risk factors. Our findings showed that WHR is the best anthropometric index for identifying men with risk factors for CVD in Iranian males, in consent to Esmaillzadeh et al. study (41); even though, in females of MASHD study, BMI was the most effective anthropometric measurement as CVD risk factor (HR and 95%CI: 1.04, 1–1.07), in contrast to women of Tehran (40).
We also found that DM was associated with nearly 2 and 3 folds higher CVD risk in males and females of the study, respectively. DM is associated with micro- and macro-angiopathies, systemic inflammation and oxidative stress which predispose the patients for developing CVD events and exacerbating the atherogenesis process (53–56). Because of the elevation of inflammatory biochemical markers like high sensitivity C-reactive protein (hs-CRP) and fibrinogen, which was reported in new-onset DM patients (57). As well, these biomarkers are enhanced in CVD patients (57, 58). Ho et al. showed in a cohort study in women with average of 8.3 years follow-up that DM patients had the similar risk for incidence of stroke (a type of CVD) compared to patients who had a history of previous stroke (59). Also, Wannamethee et al. showed in a cohort design study of men (60–79 years old) that suffering from DM increased the incidence of coronary heart disease (CHD) (60). These findings agree with our results about two genders.
MS increases the risk of CVD (particularly coronary artery disease) or stroke by three folds (28). In a 2018 systematic review, the prevalence of MS was reported up to 42 percent in the Iranian population and 15.8% of CVD burden in the Middle East was attributed to this risk factor (61). An analysis of the participants of Tehran Lipid and Glucose study showed that MS which was defined based on IDF criteria increased the risk of CVD development only in a woman (62). Our results illustrated the same findings and showed that MS was considered as a major CVD risk factor only in women. Also, in our population HTN associated with higher CVD events only in women; though, WC and DM were risk factors in both genders and dyslipidemia did not enhance the risk of CVD in both sexes. Therefore, we can imply that probably hypertension played a major role in the positive association of MS and CVD risk among females of the study. However, in other countries HTN was a CVD risk factor in males too; for instance, Sesso et al. have demonstrated in a median follow-up of 10.8 years of United States males that the average of SBP, DBP and mean arterial pressure (MAP) are strong predictor for CVD incidence in men, with higher relative risk (RR) in men younger than 60 comparing to ≥ 60 years old (63). These differences might be related to the sociocultural, ethnic and genetic determinants of different regions, worldwide (64–67). Also, in a research on the Iranian population of Tehran, it was found that female gender is a protective factor in developing HTN (68); this contrast finding in two regions of Iran (Mashhad and Tehran) may be related to lifestyle and diet habits (66).
We mentioned to genetic predisposition as an impressive factor for occurrence of CVD (67). Genetic predisposition affects the incidence of CVD by multigenic pathways (69, 70); hence, pharmacogenetics have tried to treat CVD by affecting different genes which induce CVD (70). In this study, we did not evaluate the different genes that impress CVD incidence; though, we assessed the influence of presence of positive FH of CVD as a possible predictor of CVD. Glowinska et al. demonstrated that children and adolescents with positive FH of CVD had higher BMI and lipoprotein-A level than persons with negative FH (71). Also, Wright et al. showed the effect of positive FH of CVD on the body response to stressful situations (72). They showed that persons with positive FH had higher SBP and DBP and poorer BP recovery after stress (72). In addition, Scottish people with positive FH had higher ASSIGN score (a scoring system for CVD risk) (73). Thereby, the influence of positive FH on the CVD occurrence is explained by its effect on the presence of other CVD risk factors like high BMI, lipoprotein-A level and BP.
Another finding of this study is the major protective effect of PAL against CVD incidence. This finding was expected according to previous studies (74, 75). In a 5-years cohort study of population of Denmark, it was shown that by increasing the PAL, weight, WC and DBP were decreased in both men and women, and also, HDL-C was increased in men (74). Recently, in a systematic review and meta-analysis it was demonstrated that sedentary behaviors like sitting time (ST) and television time (TT) per day had a dose-dependent association with CVD mortality in inactive persons (9–32% higher risk for ST and 3–59% higher risk for TT) (75). Therefore, enhancing the PAL can strongly reduce the CVD risk and mortality (75, 76).
The strength of the present study was documenting and following up the traditional risk factors for CVD in detail in a large population for the first time in Iran. The large sample size and type of this study make our results useful as baseline data for future research, especially focusing on WHR as a screening method for abdominal obesity. Since, World Health Organization (WHO) advocates the use of some anthropometric measurements as a screening resource for individuals under cardiometabolic risk (77). Nevertheless, there are several potential limitations that need to be addressed; although we considered all the possible risk factors in our analysis, residual unknown confounders may be still present. It is possible that genetic and environmental factors including lifestyle characteristics and certain dietary habits influence the relationships between the cardiovascular event and its risk factors.