This cross-sectional study was conducted among 423 newly diagnosed CAD patients recruited from Al-Shia Hospital, the main hospital in Gaza City, between May 2018 and July 2019.

The study protocol was approved by the Ethics Committee of Tehran University of Medical Sciences (Code: IR.TUMS.VCR.REC.1397. 636) and the Palestinian Health Research Council (Helsinki Ethical Committee of Research Code: PHRC/HC/335/18). Written informed consent was obtained from all the participants.

All patients with newly discovered CAD aged between 35 and 65 years who presented with chest pain and underwent coronary angiography were eligible for this study (Figure 1). The diagnosis of CAD was confirmed by two interventional cardiologists. However, patients with normal coronary angiography findings and established CAD (post-stent or post-coronary artery bypass graft [CABG]), renal disease, hepatic dysfunction, anemia or blood disorders, and familial hyperlipidemia were excluded from the study.

Based on baseline diagnostic coronary angiography, the severity of CAD was assessed using the Gensini score [9]. The Gensini score was calculated in three steps. First, a severity score was calculated for each coronary branch occlusion as follows: 1 point for ≤25% occlusion, 2 points for 26%–50% occlusion, 4 points for 51%–75% occlusion, 8 points for 76%–90% occlusion, 16 points for 91%–99% occlusion, and 32 points for total occlusion. For the next step, each occlusion score was multiplied by a factor according to the coronary branch (5 for the left main coronary branch; 2.5 for the proximal segment of the left anterior descending coronary branch; 2.5 for the proximal circumflex branch; 1.5 for the mid of the left anterior descending coronary branch; 1.0 for the right coronary artery, distal of the left anterior descending coronary branch, posterolateral branch, and obtuse marginal branch, and 0.5 for other branches). Finally, the Gensini score was calculated by adding the individual coronary scores. The cases were divided into two groups: severe (Gensini score ≥20) and non-severe CAD (Gensini score <20) [9].

An interview-based questionnaire was used, including patient characteristics, medical history, the Perceived Stress Scale (PSS-14), the International Physical Activity Questionnaire (IPAQ), anthropometric and blood pressure (BP) measurements, biochemical analysis, and the Gensini score for evaluating CAD severity. All measurements were standardized and validated. The data were collected by qualified data collectors who were provided explanations and trained to collect the data while respecting confidentiality.

Body weight was measured using a digital scale (Seca 808; Seca, Hamburg, Germany) to the nearest of 0.1 kg, with light clothes and no shoes. Height was measured using a stadiometer (patients barefooted and head upright) with a measuring rod attached to the balanced Seca scale to the nearest of 0.1 cm. Furthermore, non-stretch tape was used to measure waist circumference (WC), which was measured at the midpoint of the lowest rib and iliac crest at the end of expiration, using a measuring tape to the nearest of 0.1 cm. Hip circumference was measured at the widest point on the buttocks. The waist and hip circumferences were measured to the nearest 0.5 cm. Body mass index (BMI) was calculated by dividing the weight (kg) by height (m) squared. This study adopted the definition of the World Health Organization, in which BMI was categorized as normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²) and obese (≥30 kg/m²) [10]. BP (systolic and diastolic) were obtained from the left arm (mm Hg) using a validated mercury sphygmomanometer. BP was measured twice while the patient was seated after relaxing in a quiet environment, with an empty bladder. The average of the two measurements was considered the participant’s BP.

PA level was evaluated using the IPAQ-short version [11]. It has been used as an evaluation tool for PA among adults (aged 15–69 years) to estimate weekly calorie expenditure expressed as metabolic equivalents per week (METs/wk). The total IPAQ score was calculated by the summation of the duration (in minutes) and frequency (days) of walking and moderate and vigorous activities multiplied by 3.3, 4.0, and 8.0 METs, respectively. According to the IPAQ scoring system, cases were classified as insufficiently active (IA) <600 METs/wk, sufficiently active (SA) 600–1,500 METs/wk, and very active (VA) ≥1,500 METs/wk.

Perceived stress status was assessed on the day after coronary angiography by using the PSS, which has been translated and validated in Arabic language [12]. It measures the degree to which an individual experienced stress in their life during the previous month. It is a 14-item, 5-point Likert scale (0, never; 1, almost never; 2, sometimes; 3, fairly often; and 4, often). The detail items of the PSS scoring system are items 4, 5, 6, 7, 9, 10, and 13 as reversing scores (0=4, 1=3, 2=2, 3=1, and 4=0). The range of possible PSS scores were from 0 to 56.

The Arabic version of the PSS and PA questionnaires were used, with an intra-correlation coefficient of 0.90 and 0.8, respectively [11,12]. The content validity of the Arabic questionnaire was reviewed by a panel of experts. The required changes were made to clear any ambiguity and ensure comprehension by Palestinian participants after the pilot study.

A reliability test was performed for the overall Arabic version of the questionnaire items, where the values of the Cronbach’s α test for PSS and PA were 0.710 and 0.731, respectively, which indicates high and acceptable internal consistency of the data and its validity for model analysis.

After 12 hours of fasting, venous blood samples were collected from all patients on the day after coronary angiography by well-trained and expert nurses. Venous blood (4.0 mL) was drawn into vacationer tubes. Serum was separated immediately, which was was analyzed for fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). A Mindray BS-200 chemistry analyzer (Mindray DS USA Inc., Mahwah, NJ, USA) was used for blood chemistry analysis. Laboratory tests were conducted in a privately licensed laboratory.

Data were analyzed using the IBM SPSS ver. 24.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics (frequencies and cross-tabulations) were used to describe the main features of the data. Chi-square tests were used to assess the first-hand relationships between the response variables and categorical variables. However, an independent Student t-test was used to assess the relationships between the response variables and continuous variables. Univariate binary logistic regression was performed to assess the magnitude of the relationship between variables by odds ratio (OR) with a 95% confidence interval (95% CI). The obtained OR for the severity of CAD was evaluated using the following predictors: PSS was used as continuous and PA level was categorized as IA (<600 METs/wk), SA (600–1,500 METs/wk), and VA (≥1,500 METs/wk). The lowest category of PA was used as the reference. Multivariable binary logistic regression was performed using the backward stepwise elimination method at a level of 0.2. The following confounding factors were identified as significant factors in the univariate analysis and put in and adjusted for in the multivariable model: age, sex, marital status, years of education, history of hypertension, systolic BP, family history of CAD, current smoking, dietary supplements, and BMI. Statistical significance was set at P<0.05.

This study included 423 patients who were newly diagnosed with CAD. The CAD diagnosis was confirmed using coronary angiography results. CAD severity was dichotomized by the Gensini score into severe and non-severe, which accounted for 63.8% (270) and 36.2% (153), respectively. The mean age of participants was 56.7 years with a standard deviation (SD) of 5.9. The proportion of severe CAD among men (86.7%) was higher than that among women. The majority (95.2%) of patients with severe CAD were married. About two-thirds (71.2%) of the participants had only a school education, and 66.3% of them had severe CAD compared with those with university education.

Regarding monthly income, 71.6% of the participants were below the poverty line ≤$550; however, the distribution of CAD severity between low and high monthly income was relatively equal. In addition, 56% of all participants had a family history of CAD, and 58.9% of them had severe CAD. More than half (51.5%) of the participants were current smokers, and 61.5% of them had severe CAD. Concerning comorbidities, 57.9% of the participants had a history of hypertension, and 54.1% of them had severe CAD. The overall mean±SD systolic BP of participants was 138.94±18.57 mm Hg, which was higher among severe CAD 141.75±18.38 mm Hg compared with among non-severe CAD cases. Approximately 48.7% of the participants had a history of DM, and 49.3% of them were classified as having severe CAD. Majority of the participants (96.5%) did not use dietary supplements. Moreover, our results revealed that 45.2% and 46.5% of all participants were overweight and obese, respectively, and the percentage of obese individuals was much higher (74.1%) among severe CAD cases than among non-severe cases (25.9%). Additionally, the mean WC was greater in the severe CAD group than in the non-severe group (Table 1).

The relationships between CAD severity and the distributions of categorical independent variables were assessed using the chi-square test. The findings revealed significant statistical associations among sex, marital status, educational level, smoking status, history of hypertension, use of dietary supplements, and BMI categories comparing severe CAD with non-severe. An independent Student t-test was used for continuous variables, which detected significant differences among the mean systolic BP, BMI, and WC. Furthermore, our results showed that the mean differences in lipid profiles and glucose levels among patients with severe CAD were not significantly different from those in patients with non-severe CAD (Table 1).

The results in Table 2 demonstrate that the mean±SD total PSS score of the patients was 27.86±4.57. The score was slightly higher among the severe CAD group (28.22±4.53) compared with among the non-severe (27.86±4.61); this difference was statistically significant between the CAD severity groups (P=0.034). On the other hand, the results in Table 2 show that the percentages of SA, active, and IA categories of PA were higher among severe CAD cases than among non-severe CAD cases. These differences were statistically significant (P<0.001). Moreover, because of known sex variation in CAD [13], subgroup analysis and stratification by sex were conducted. The results illustrated that, in PSS, a statistically significant mean difference was found among women when comparing severe with non-severe CAD cases (P=0.004). However, in the PA categories, a relationship was detected among men when comparing severe with non-severe CAD cases (P=0.001).

We used binary logistic regression to assess the baseline association between PSS, PA levels, and CAD severity, which was dichotomized into severe and non-severe (Table 3). The univariate regression analysis showed that the odds of CAD severity were significantly increased by 5% for each score increase in the PSS (OR, 1.05; 95% CI, 11.02–1.09; P=0.035). Regarding the association between PA levels and the severity of CAD, the analysis showed that the odds of severity of CAD among VA patients was decreased by 62% compared with among the IA patients; however, this association was not statistically significant at the 0.05% level (OR, 0.62; 95% CI, 0.37–1.07; P=0.088). In contrast, the odds of CAD severity significantly increased by 74% among SA patients compared with among the IA patients (OR, 1.74; 95% CI, 1.02–2.97; P=0.040). Moreover, univariate regression analysis revealed that the odds of CAD severity were significantly increased by the following predictors: male sex, being married, university education, current smoking, obesity, increased systolic BP, and WC. However, it decreased with the use of dietary supplements and a history of hypertension of at least 3 months under treatment (Table 3).

Multivariable logistic regression was performed to assess the simultaneous association between the severity of CAD as a response variable and all other independent variables, including PSS and PA, which showed statistical inferences in univariate regression (Table 3). Keeping all other variables constant at baseline, the results showed that PSS, PA level, age, sex, smoking status, history of hypertension, systolic BP, and BMI were predictors of CAD severity. Thus, the odds of CAD severity markedly increased compared with that in univariate regression to 9% when the PSS increased by one score (OR, 1.09; 95% CI, 1.01–1.14; P=0.030). Interestingly, the odds of CAD severity among SA individuals were significantly changed in multivariable regression to a protective factor, in which the adjusted OR declined to 43% when comparing SA to IA patients with a significant statistical inference (OR, 0.43; 95% CI, 0.23–0.72; P=0.027). In addition, the adjusted OR of CAD severity dropped to 0.54, when comparing VA to SA patients with a notable linear association in protection ability; however, this association was not statistically significant (OR, 0.54; 95% CI, 0.24–1.87; P=0.390).

Regarding other confounding variables, the multivariable regression analysis showed that the odds of CAD severity significantly increased by 5% when the age increase by 1 year (OR, 1.05; 95% CI, 1.01–1.10; P=0.049). Moreover, the OR of severe CAD among men was 5.64 greater than that among women (OR, 5.64; 95% CI, 2.98–10.68; P<0.001). In addition, the odds of CAD severity among current smokers dropped in multivariable regression to 75% compared with that in univariate analysis, in which the association remained significantly higher among smokers compared with among non-smokers (OR, 1.75; 95% CI, 1.01– 3.50; P<0.001). Furthermore, the odds of CAD severity significantly increased by 29% when the systolic BP increase by 1 mm Hg (OR, 1.29; 95% CI, 1.14–1.44; P<0.001). However, the odds of severe CAD increased by 2.45 times among obese patients compared with among those with normal BMI (OR, 2.45; 95% CI, 1.02–5.85; P<0.001). The odds of CAD severity decreased by 48% in patients with a history of hypertension and under treatment for at least 3 months with no history of hypertension (OR, 0.48; 95% CI, 0.25–0.79; P=0.005). In addition, a subgroup multivariable logistic regression analysis was conducted to determine the association between CAD severity and sex variation (Table 4). The results showed that the adjusted OR of PSS total score was 27% higher among severe CAD females patients compared with among the non-severe CAD female patients (OR, 1.27; 95% CI, 1.11– 1.46; P<0.001); however, no association was found among men. In contrast, the adjusted OR of PA categories was protective by 16% among men when comparing IA to SA (OR, 0.16; 95% CI, 1.06–0.34; P=0.035); however, no association was found among women.