The aim of the present work was to compare the influence of classic cardiovascular disease (CVD) risk factors on the development of acute coronary syndrome (ACS) and ischemic stroke. During 2009–2010, 1,000 participants were enrolled: 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke, and 500 were population-based, control subjects, 1-for-1 matched to the patients by age and gender. The following CVD risk factors were evaluated: smoking/passive smoking, family history of CVD, physical inactivity, hypertension, hypercholesterolemia, diabetes mellitus, presence of overweight and obesity, trait anxiety (assessed with the Spielberger State-Trait Anxiety Inventory form Y-2), and adherence to the Mediterranean diet (assessed by the MedDietScore). Furthermore, participants graded the perceived significance of the aforementioned factors, using a scale from 1 (not important) to 9 (very important). The risk factors with the highest effect size for ACS, as determined by the Wald criterion, were smoking and hypercholesterolemia; regarding stroke, they were anxiety and family history of CVD (all p <0.01). When the odds ratios of each factor for ACS and stroke were compared, insignificant differences were observed, except for smoking. On the basis of the participants’ health beliefs, smoking and stress emerged as the most important risk factors, whereas all subjects graded passive smoking as a least important factor. In conclusion, similarities of the risk factors regarding ACS and ischemic stroke facilitate simultaneous primary prevention measures.
The aims of the present study were to compare the effect of individual cardiovascular disease (CVD) risk factors on the occurrence of acute coronary syndrome (ACS) versus ischemic stroke and to evaluate the perceived importance of CVD risk factors in a sample of 1,000 CVD patients and healthy subjects.
Methods
This was a multicenter, case-control study with individual (1-for-1) matching by age (within ± 3 years) and gender. From October 2009 to December 2010, 500 of the 615 consecutive patients with a first ACS event (n = 250, 209 acute myocardial infarction, 41 unstable angina) or ischemic stroke (n = 250) and without any suspicion of previous CVD who presented to the cardiology or pathology clinics or emergency units of 3 major general hospitals in Greece agreed to participate (participation rate 81%). For the stroke patients who were unable to communicate (speech disorders, aphasia, memory problems), the information was obtained by a valid surrogate respondent (first-degree relative living in the same home as the patient and aware of the participant’s dietary habits and medical history). Patients with chronic neoplasmatic disease or chronic inflammatory disease, as well as individuals with recent changes in their dietary habits, were not enrolled in the study. Five hundred control subjects (250 matched 1-for-1 with ACS patients and another 250 matched 1-for-1 with stroke patients) were selected concurrently with the patients on a volunteer, population basis and from the same region as the patients. Controls were without any clinical symptoms or suspicions of CVD in their medical history, as assessed by a physician.
On the basis of a priori statistical power analysis, a sample size of 500 patients (250 ACS, 250 stroke) and 500 age- and gender-matched healthy subjects, was adequate to evaluate 2-sided odds ratios (ORs) equal to 1.20, achieving statistical power >0.80 at 0.05 probability level (p value).
The study was approved by the Ethics Committee of the University Hospital of Ioannina and was carried out in accordance with the Declaration of Helsinki (1989) of the World Medical Association. Before collection of any information, participants (or valid surrogate respondents) were informed about the aims and procedures of the study and provided their signed consent.
Regarding the ACS patients, clinical symptoms were evaluated at hospital entry and a 12-lead electrocardiogram was performed. Evidence of myocardial cell death was assessed with blood tests and measurement of the levels of troponin I and the MB fraction of total creatinine phosphokinase (according to the Universal Definition of Myocardial Infarction, Joint European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force) ; unstable angina was defined by the occurrence of ≥1 angina episode(s), at rest, within the preceding 48 hours, corresponding to class III of the Braunwald classification. Ischemic strokes were defined through symptoms of neurologic dysfunction of acute onset of any severity, consistent with focal brain ischemia and imaging/laboratory confirmation of an acute vascular ischemic pathology.
Dietary habits of the past year were assessed through a 90-item, validated semiquantitative food frequency questionnaire that has been previously described. Level of adherence to the Mediterranean diet was evaluated using an 11-item large-scale composite index, the MedDietScore. The theoretical range of the MedDietScore was between 0 and 55. Higher values of this diet score indicate greater adherence to the Mediterranean diet. The validation properties of the MedDietScore have been presented elsewhere in the literature.
Sociodemographic variables recorded were age and gender (for the matching procedure). Current smokers were defined as those who smoked at least 1 cigarette per day, former smokers as those who had stopped smoking more than 1 year previously, and the rest of the participants were defined as noncurrent smokers. Passive smokers were defined as those who were exposed to the smoke of others (colleagues, partner, parents, children, roommates) for >30 minutes per day. A new variable was then developed, including the following categories: no smoker/no passive smoker, no smoker/passive smoker, ever smoker (i.e., current and former smoker)/no passive smoker, ever smoker/passive smoker. Physical activity was assessed using the International Physical Activity Questionnaire index, which has been validated for the Greek population. According to their physical activity levels, participants were classified as inactive or physically active (moderate or vigorously active). Body mass index (BMI) was calculated as weight (in kilograms) divided by standing height (in meters squared); overweight and obesity were defined as BMI 25.0 to 29.9 kg/m 2 and >29.9 kg/m 2 , respectively.
Detailed medical history was recorded for all participants, including family history of CVD and personal and family history of hypertension, hypercholesterolemia, hypertriglyceridemia, and diabetes. Patients whose average blood pressure levels were ≥140/90 mm Hg or were under antihypertensive medication were classified as having hypertension. Hypercholesterolemia was defined as total serum cholesterol levels >200 mg/dl or the use of lipid-lowering agents, and diabetes mellitus was defined as fasting blood glucose ≥126 mg/dl or the use of antidiabetic medication. A previously translated and validated version of the Spielberger Trait Anxiety Inventory (STAI form Y-2, range 20–80) was used for the assessment of trait anxiety.
Participants were asked to grade in a 9-unit scale (i.e., 1 = not important to 9 = extremely important) the significance of 8 traditional CVD risk factors: active smoking, exposure to passive smoking, physical inactivity, stress, unhealthy dietary habits, and presence of overweight/obesity, hypertension, hypercholesterolemia, diabetes mellitus, and family history of CVD.
Normally distributed continuous variables (age, BMI, MedDietScore, STAI Y-2, participants’ beliefs) are presented as mean values ± SD and categorical variables (gender, smoking habits, physical activity, medical history, BMI categories, MedDietScore categories, and STAI Y-2 categories) as frequencies. Associations between categorical variables were tested by the calculation of the chi-square test. Comparisons of mean values of normally distributed continuous variables by clinical outcome were performed using Student’s t test. Correlations between continuous variables were evaluated using the Pearson’s r or Spearman rho coefficients. Normality of the variables was tested using P-P plots. Estimations of the relative odds of having ACS or stroke according to the exposure measurements were performed through conditional logistic regression analysis; results are presented as ORs and the corresponding 95% confidence intervals (CIs). The Hosmer-Lemeshow statistic was calculated to evaluate model’s goodness-of-fit. Comparisons between the effect size measures (i.e., ORs) of the 2 logistic models (1 for ACS and 1 for stroke) were based on the Wald test (i.e., log[OR]/Var[log OR]; the higher, the better), which incorporates the estimated effect parameter in relation to its variance and thus standardizes the effect. The likelihood-ratio test was also used to confirm the previous results. The comparison regarding the ORs of each CVD risk factor between the 2 models (i.e., ACS and stroke) was performed using cross-model postestimation tests. All reported p values were based on 2-sided hypotheses. SPSS 18.0 software (SPSS Inc., Chicago, Illinois) was used for all the statistical calculations.
Results
Demographic, clinical, psychological, and nutritional characteristics of the participants are presented in Table 1 . Patients (with both ACS and stroke) tended to be less physically active than the control participants, with higher prevalence of almost all traditional cardiovascular risk factors: hypercholesterolemia, hypertension, diabetes mellitus, anxiety, unhealthy dietary patterns, and family history of CVD.
| Variable | ACS Patients (n = 250) | ACS Controls (n = 250) | Stroke Patients (n = 250) | Stroke Controls (n = 250) |
|---|---|---|---|---|
| Age (yrs) | 60 ± 12 | 60 ± 12 | 77 ± 9 | 73 ± 9 |
| Men | 208 (83.2%) | 208 (83.2%) | 139 (55.6%) | 139 (55.6%) |
| Smoking habits | ||||
| No smoker/no passive smoker | 20 (8.4%) ∗ | 62 (26.4%) | 59 (33.7%) | 77 (33.2%) |
| No smoker/passive smoker | 32 (13.4%) | 37 (15.7%) | 38 (21.7%) | 51 (22.0%) |
| Ever smoker/no passive smoker | 37 (15.5%) | 45 (19.1%) | 24 (13.7%) | 27 (11.6%) |
| Ever smoker/passive smoker | 150 (62.5%) | 91 (38.7%) | 54 (30.9%) | 77 (33.2%) |
| Physical inactivity | 84 (35.9%) ∗ | 43 (17.5%) | 111 (52.9%) ∗ | 61 (25.2%) |
| Family history of CVD | 81 (36.2%) ∗ | 39 (16.7%) | 51 (31.3%) ∗ | 38 (16.7%) |
| Hypertension | 148 (62.2%) ∗ | 90 (37.7%) | 206 (84.4%) ∗ | 137 (56.8%) |
| Hypercholesterolemia | 165 (71.4%) ∗ | 100 (45.5%) | 159 (68.5%) † | 119 (54.1%) |
| Diabetes mellitus | 58 (26.1%) ∗ | 29 (12.4%) | 71 (32.9%) † | 50 (21.5%) |
| Body mass index (kg/m 2 ) | 27.82 ± 4.29 | 27.23 ± 3.50 | 26.72 ± 3.57 | 27.35 ± 4.24 |
| Normal weight (18.5–24.9) | 57 (24.9%) | 63 (26.3%) | 79 (33.1%) | 73 (30%) |
| Overweight (25–29.9) | 116 (50.7%) | 132 (55%) | 124 (51.9%) | 120 (49.4%) |
| Obese (>30) | 56 (24.5%) | 45 (18.8%) | 36 (15.0%) | 50 (20.6%) |
| MedDietScore (range 0–55) | 30.67 ± 5.02 ∗ | 32.50 ± 4.41 | 29.99 ± 3.79 ∗ | 32.03 ± 4.08 |
| First tertile (0–29) | 86 (41.1%) ∗ | 50 (21.9%) | 94 (49.5%) ∗ | 60 (26.8%) |
| Second tertile (30–33) | 66 (31.6%) | 79 (34.6%) | 64 (33.7%) | 82 (36.6%) |
| Third tertile (34–55) | 57 (27.3%) | 99 (43.4%) | 32 (16.8%) | 82 (36.6%) |
| STAI Y-2 (range 20–80) | 40.52 ± 10.05 ∗ | 36.55 ± 9.26 | 45.66 ± 7.17 ∗ | 38.65 ± 9.86 |
| 20–39: low anxiety | 109 (48.7%) ∗ | 158 (64.5%) | 37 (17.9%) ∗ | 135 (54.9%) |
| 40–59: moderate anxiety | 105 (46.9%) | 84 (34.3%) | 167 (80.7%) | 106 (43.1%) |
| 60–80: severe anxiety | 10 (4.5%) | 3 (1.2%) | 3 (1.4%) | 5 (2%) |
∗ p <0.001 compared with the ACS or stroke control group, respectively.
† p <0.05 compared with the ACS or stroke control group, respectively.
Results from the multivariable models regarding ACS and stroke, including traditional CVD risk factors, are presented in Table 2 . Of the factors associated with the odds of having an ACS, the most significant (in terms of effect size measure) was smoking—in particular, being both a smoker and a passive smoker. Hypercholesterolemia was the second most significant factor, followed by hypertension. Regarding stroke, anxiety emerged as the most significant factor, followed by family history of CVD and adherence to the Mediterranean diet.
| Independent Variables | ACS | Stroke | p | ||
|---|---|---|---|---|---|
| OR (95% CI) | Wald | OR (95% CI) | Wald | ||
| MedDietScore (per 1/55 unit) | 0.93 (0.88–0.99) | 5.98 | 0.91 (0.84–1.00) | 4.12 | 0.710 |
| Physical inactivity (yes/no) | 2.94 (1.47–5.88) | 9.22 | 1.97 (0.91–4.26) | 2.96 | 0.414 |
| Smoking habits | |||||
| No smoker/no passive smoker (reference) | 1.00 | — | 1.00 | — | — |
| No smoker/passive smoker | 4.33 (1.52–12.38) | 7.49 | 1.32 (0.55–3.18) | 0.37 | 0.054 |
| Ever smoker/no passive smoker | 5.15 (1.82–14.53) | 9.57 | 1.69 (0.43–6.69) | 0.55 | 0.127 |
| Ever smoker/passive smoker | 8.62 (3.52–21.14) | 22.16 | 0.75 (0.29–1.94) | 0.35 | <0.001 |
| Family history of CVD (yes/no) | 2.40 (1.23–4.69) | 6.63 | 2.35 (1.07–5.17) | 4.51 | 0.960 |
| Hypertension (yes/no) | 2.81 (1.52–5.21) | 10.75 | 1.60 (0.74–3.44) | 1.45 | 0.223 |
| Hypercholesterolemia (yes/no) | 3.80 (2.15–6.68) | 21.31 | 1.86 (0.89–3.87) | 2.75 | 0.090 |
| Diabetes mellitus (yes/no) | 1.91 (0.88–4.15) | 2.68 | 1.31 (0.60–2.86) | 0.45 | 0.483 |
| Overweight/obese (yes/no) | 0.56 (0.29–1.08) | 2.99 | 1.00 (0.44–2.24) | <0.001 | 0.236 |
| STAI-Y2 (per 1/80 unit) | 1.04 (1.01–1.07) | 5.48 | 1.06 (1.02–1.10) | 8.92 | 0.257 |
To examine whether the risk factors exerted a similar or different impact on the 2 CVD manifestations (i.e., ACS or ischemic stroke), the ORs between the 2 models were compared. Insignificant differences were observed for the majority of the risk factors included in the models, except for smoking habits. Furthermore, an estimation of the attributable risk for ACS or stroke, for each risk factor was calculated (continuous variables were transformed into categorical ones). Results are presented in Figure 1 .
In Table 3 , the health beliefs of the participants concerning the common CVD risk factors are presented. All grades were >5 (on a 9-unit scale), reflecting that all participants recognized the detrimental influence of these factors on their health status. The ACS patients reported that the most important factor influencing CVD development was stress, followed by smoking and unhealthy dietary habits, whereas the ACS controls concluded that smoking was the most detrimental factor, along with stress and overweight or obesity. The stroke patients recognized the presence of hypertension, hypercholesterolemia, and diabetes as most important, followed by smoking, and then stress. For the stroke control participants, smoking was the most important factor, followed by stress and being overweight or obese. However, even though smoking was considered as 1 of the most important CVD risk factors, passive smoking was graded as 1 of the least important ones by all patient and control groups. Furthermore, the ACS patients tended to underestimate the role of the risk factors, compared with their control participants, but this was not observed between the stroke patients and control participants. Finally, stroke patients had higher scores for the majority of the factors evaluated compared with the ACS patients.
| ACS Patients (n = 250) | ACS Controls (n = 250) | Stroke Patients (n = 250) | Stroke Controls (n = 250) | |
|---|---|---|---|---|
| Health belief: Smoking | 7.03 ± 2.53 ∗ † | 7.62 ± 1.81 | 7.68 ± 2.32 | 7.61 ± 1.96 |
| Ever smoker | 7.24 ± 2.37 ∗ † ‡ | 7.69 ± 1.59 | 7.86 ± 2.03 | 7.31 ± 2.05 ‡ |
| No smoker | 6.29 ± 2.95 ∗ † | 7.53 ± 2.07 | 7.57 ± 2.48 | 7.89 ± 1.77 |
| Health belief: passive smoking | 5.94 ± 2.54 †† | 6.23 ± 2.04 | 6.88 ± 2.24 | 6.49 ± 2.12 |
| Passive smoker | 6.02 ± 2.56 | 6.25 ± 2.13 | 6.66 ± 3.35 | 6.51 ± 2.17 |
| No passive smoker | 5.67 ± 2.61 † | 6.25 ± 2.02 | 6.72 ± 2.44 | 6.63 ± 1.99 |
| Health belief: physical inactivity | 6.07 ± 2.32 ∗∗†† | 6.83 ± 1.69 | 6.88 ± 2.08 | 6.71 ± 1.89 |
| Physically active | 6.10 ± 2.33 ∗ | 6.83 ± 1.72 | 6.55 ± 2.24 | 6.68 ± 1.99 |
| Sedentary | 5.96 ± 2.22 ∗ † | 6.76 ± 1.56 | 6.92 ± 2.01 | 6.83 ± 1.56 |
| Health belief: stress | 7.76 ± 1.72 | 7.54 ± 1.58 | 7.60 ± 1.68 | 7.48 ± 1.63 |
| Low stress | 7.68 ± 1.78 | 7.71 ± 1.47 ‡ | 6.69 ± 2.73 ‡ | 7.73 ± 1.55 ‡ |
| Moderate/severe stress | 7.92 ± 1.64 ∗ | 7.25 ± 1.71 | 7.79 ± 1.38 ∗ | 7.18 ± 1.67 |
| Health belief: unhealthy dietary habits | 6.88 ± 2.19 ∗ | 7.25 ± 1.61 | 7.20 ± 2.10 | 7.28 ± 1.65 |
| MedDietScore ≥ 32 | 7.42 ± 1.70 ‡ | 7.28 ± 1.61 | 6.49 ± 2.93 | 7.25 ± 1.63 |
| MedDietScore < 32 | 6.59 ± 2.42 ∗ † | 7.50 ± 1.37 | 7.28 ± 1.98 | 7.48 ± 1.57 |
| Health belief: overweight/obesity | 6.63 ± 2.36 ∗ † | 7.39 ± 1.65 | 7.40 ± 2.29 ∗ | 7.29 ± 1.70 |
| BMI < 25 kg/m 2 | 6.31 ± 2.78 ∗ | 7.53 ± 1.51 | 6.89 ± 2.67 ‡ | 7.25 ± 1.76 |
| BMI ≥ 25 kg/m 2 | 6.75 ± 2.14 ∗ †† | 7.39 ± 1.58 | 7.72 ± 1.98 | 7.34 ± 1.63 |
| Health belief: diabetes mellitus/hypercholesterolemia/hypertension | 6.56 ± 2.46 ∗ †† | 7.24 ± 1.78 | 7.69 ± 2.08 ∗ | 7.18 ± 1.82 |
| Presence | 6.63 ± 2.48 ∗ †† | 7.27 ± 1.66 | 7.78 ± 1.95 ∗ | 7.22 ± 1.79 |
| Absence | 6.52 ± 2.27 | 7.29 ± 1.95 | 8.50 ± 1.00 | 7.30 ± 1.76 |
| Health belief: family history of CVD | 5.96 ± 2.54 ∗ †† | 6.47 ± 2.16 | 6.87 ± 2.25 | 6.48 ± 2.20 |
| Yes | 6.82 ± 2.19 ‡ | 6.97 ± 2.07 | 6.71 ± 2.61 | 7.41 ± 1.86 ‡ |
| No | 5.53 ± 2.61 ∗ † | 6.34 ± 2.22 | 6.72 ± 2.40 | 6.31 ± 2.26 |
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