Association Between Behavior-Dependent Cardiovascular Risk Factors and Asymptomatic Carotid Atherosclerosis in a General Population
Background and Purpose— Physical inactivity and unfavorable dietary and lifestyle patterns are related to cardiovascular disease and premature death. Their relationship to atherosclerosis of the carotid arteries and subsequent stroke is unclear. The objective of this study was to investigate the association between those behavioral cardiovascular risk factors and asymptomatic atherosclerosis of the carotid arteries in a population of former East Germany.
Methods— The Study of Health in Pomerania (SHIP) is a cross-sectional survey in northeast Germany. In 1632 individuals aged 45 to 70 years, high-resolution B-mode ultrasound was used to assess the mean intima-media thickness of the right and left common carotid arteries. Carotid plaques and stenosis were recorded. Physical activity, dietary patterns, and cardiovascular risk factors were assessed in interviews with the use of standardized scales. Physically active participants with optimal dietary patterns were classified in the optimal lifestyle group, and those inactive with unfavorable diet were classified in the unfavorable group.
Results— After adjustment for sex and age, significant decreasing trends were found for both intima-media thickness and severe asymptomatic atherosclerosis from unfavorable to optimal lifestyle patterns in never smokers but not in smokers. Regression analysis revealed an increased risk of severe asymptomatic atherosclerosis in subjects with an unfavorable lifestyle pattern compared with those with an optimal pattern (odds ratio 2.68; 95% CI, 1.13 to 6.37), following a significant linear trend.
Conclusions— Physical activity and optimal diet are associated with reduced risk of early atherosclerosis in subjects who never smoked, while no benefit of an otherwise optimal lifestyle is observed in smokers.
Cardiovascular diseases are the most common causes of death and disability in industrialized countries.1 Atherosclerosis combines a cascade of different pathophysiological mechanisms and is the main factor leading to myocardial infarction or stroke. It develops as a result of chronic alterations of the vessel wall due to atherogenic risk factors such as elevated blood pressure or high blood lipid levels. Many of these atherogenic factors are influenced by lifestyle habits. Smoking has been found to be positively associated and alcohol consumption to be negatively associated with atherosclerosis of the carotid arteries. However, evidence relating physical activity and dietary and lifestyle patterns to stroke incidence and carotid atherosclerosis is inconclusive.2–8⇓⇓⇓⇓⇓⇓
An increased carotid artery intima-media thickness (IMT) has been associated with unfavorable cardiovascular risk factor levels, prevalent cardiovascular and cerebrovascular disease, and atherosclerosis in other parts of the arterial system. Increased IMT serves not only as a valid marker of generalized atherosclerosis9,10⇓ but also as a predictor for incident myocardial infarction and stroke.11–14⇓⇓⇓ Therefore, interest has been shifted from clinical end points, which are defined only by the presence or absence of clinical events, to intermediate end points such as carotid artery IMT. The latter allows the assessment of atherosclerosis before clinical events and measures the dependent variable on a continuous scale.
The aim of our study was to investigate the association between dietary pattern, physical activity, smoking, and asymptomatic atherosclerosis of the carotid arteries in participants of the Study of Health in Pomerania (SHIP), a general health survey in former East Germany.15
Subjects and Methods
Study Design and Subjects
The SHIP is a cross-sectional population survey in the northeast region of Germany, involving the 3 cities Greifswald, Stralsund, and Anklam and 29 surrounding communities.15 From the total population of 212 157 living in the study area, a representative population sample totaling 7008 persons aged 20 to 79 years was selected from population registers. The 2-stage cluster sampling method was adopted from the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project Augsburg, Germany,16,17⇓ and yielded twelve 5-year age strata (20 to 79 years) for both sexes, each including 292 individuals.
Ultrasound measurements of carotid arteries were restricted to groups aged 45 to 70 years (1943 persons; response rate 71%). Included in the present analysis were 860 women and 772 men aged 45 to 70 years with no history of myocardial infarction or stroke and with complete information on behavioral factors, comorbidities, and anthropometric measurements.
Data collection was done between October 1997 and May 2001 after written consent was obtained from each participant. In computer-aided face-to-face interviews, sociodemographic factors, medical histories, and behavioral risk factors were assessed.
Symptoms, Preexisting Disease, and Lifestyle Factors
Leisure time physical activity was defined by 2 questions according to the MONICA Augsburg algorithm.18 Physically active individuals participated in sports in summer and in winter in at least 1 season for >1 hour per week. The mean daily alcohol consumption for the last month was calculated by the beverage-specific quantity/frequency method: number of days with alcohol intake (subdivided into 3 beverage types: beer, wine, spirits). The values are expressed in grams of pure alcohol per day.15
A food frequency questionnaire19 was applied in the computer-aided interview. The use of selected food groups was classified according to the recommendations of the German Society of Nutrition (Table 1).20 The classifications per food category (food frequency patterns [FFP]) were summarized to a summary score (dietary pattern) per subject. Sex-specific tertiles of this score reflected the quality of food intake: lower tertile=unfavorable dietary pattern (score <15 for men, <17 for women); medium tertile=normal dietary pattern (score 15 to 16 for men, 17 to 18 for women); and upper tertile=optimal dietary pattern (score >16 for men, >18 for women).
We classified all participants into 3 lifestyle categories according to their leisure time physical activity and their food intake. Physically active subjects with an optimal or normal FFP were classified as having an optimal lifestyle. A moderate lifestyle was defined as either no physical activity and optimal/normal FFP or as physically active and an unfavorable FFP. Finally, subjects with no physical activity and an unfavorable FFP were classified as having an unfavorable lifestyle.
Systolic and diastolic blood pressure was measured. Prevalent hypertension was defined as systolic blood pressure ≥60 mm Hg and/or diastolic blood pressure ≥95 mm Hg. Body mass index (BMI) was computed from body height and weight (weight [kg]/(height [m]2).
Trained and certified technicians (observer) scanned the extracranial carotid arteries bilaterally with B-mode ultrasound using a 5-MHz linear-array transducer and a high-resolution instrument (DIASONICS VST Gateway) for plaque and/or stenosis occurrence in the common carotid artery (CCA), the bifurcation, and the internal and external carotid arteries. Carotid stenosis was defined by a continuous-wave Doppler-quantified occlusion of at least 50% in 1 of these carotid artery segments. Scans from the distal straight portion (1 cm in length) of both CCAs were recorded, and the mean far-wall IMT was calculated by averaging the 10 consecutive measurement points (in 1-mm steps) from the bulb of both sides by trained and certified readers.
Within- and between-reader (reading of a given duplicate set of 25 scans) and -observer (duplicate mean IMT measurements in 5 subjects) variabilities were tested by semiannual certification procedures.21 The Spearman correlation coefficients for intraobserver and intrareader measurements were >0.95 and >0.97, respectively, and the mean differences (±2 SD) were <1% (<10%). Spearman correlation coefficients for between-observer and between-reader variabilities were >0.90 and >0.95, respectively, and the mean differences (±2 SD) were <5% (<15%). In 48 subjects, missing data occurred in the IMT measurements by exclusion criteria (bandages, dressings, scars, vessel kinking, or ultrasound image quality does not meet the reading criteria), and 1 participant refused the examination. Prevalent asymptomatic carotid atherosclerosis was defined by a mean carotid IMT >1.0 mm and either plaque occurrence in at least 2 locations on 1 side (left or right) or the occurrence of a stenosis >50% in the left or right CCA.
ANOVA was used to compare continuous variables across groups, and Cochran-Mantel-Haenszel statistics were used to compare adjusted prevalence estimates across groups. Logistic regression analysis was applied to fit models of asymptomatic carotid atherosclerosis as a function of potential cardiovascular risk factors and control variables. The Wald χ2 statistic was used to test for a linear trend across the categories of ordinary variables. The analyses were performed by PROC FREQ (CMH option), PROC GLM, and PROC LOGISTIC of the SAS 8.1 software system.22
Our analysis was restricted to 1632 study participants aged 45 to 70 years. Sociodemographic parameters, clinical characteristics, behavioral risk factors, and the relations between lifestyle patterns and known cardiovascular risk factors in this population are presented in Tables 2 and 3⇓. All but 1 (diastolic blood pressure) of the documented cardiovascular risk factors were slightly more favorable in the optimal lifestyle group. However, these differences did not reach statistical significance, with the exception of BMI.
Former and current smokers had similar values for mean IMT (0.765 versus 0.782 mm; P<0.10), plaque prevalence (64.7% versus 63.1%; P<0.13), and carotid artery stenosis (2.6% versus 3.2%; P<0.34) even after adjustment for sex and age. Thus, for further analysis the 2 groups were collapsed. Compared with this collapsed smoker group, subjects who never smoked had significantly reduced mean IMT (0.745 versus 0.766 mm; P<0.01) and a significantly lower prevalence of plaques (58.7% versus 64.1%; P<0.03) and stenosis (0.9% versus 2.8%; P<0.01). Because of the strong associations between smoking and asymptomatic atherosclerosis, results for never smokers and the collapsed smoker group are presented separately in Table 4. No relation between age- and sex-adjusted mean IMT values, severe asymptomatic atherosclerosis, physical activity, alcohol intake, and dietary or lifestyle pattern could be found in smokers. However, never smokers with unfavorable FFP had higher mean IMT values than those with optimal FFP (0.750 versus 0.723 mm; P<0.04). Additionally, never smokers with unfavorable lifestyle patterns had higher mean IMT values than those with moderate (0.757 versus 0.725 mm; P<0.01) and optimal lifestyle patterns (0.757 versus 0.729 mm; P<0.05). Furthermore, significant decreasing trends across categories of dietary and lifestyle patterns were observed for IMT (P<0.02) and for asymptomatic carotid atherosclerosis (P<0.02), from the unfavorable to the optimal category. Among never-smoking subjects with low alcohol intake, the IMT was higher, but neither the estimates nor the trend across categories was significantly different.
The relationship between cardiovascular risk factors and common carotid IMT was determined by multiple regression with the use of 2 different regression models, both controlled for age, sex, diabetes, systolic blood pressure, serum cholesterol, smoking, and alcohol intake (Table 5). The first model included physical activity and dietary pattern as distinct variables. The second model replaced both factors with the classification into lifestyle pattern based on both variables. Significantly positive associations between IMT and age, male sex, diabetes, systolic blood pressure, serum cholesterol, and smoking as well as a significant trend across the smoking and the alcohol consumption categories were observed. No significant association between IMT and physical activity, dietary patterns, and lifestyle patterns were found.
Table 6 presents risk factors associated with asymptomatic carotid atherosclerosis with the use of the same models as defined for Table 5. In the first model, an increase in age by 5 years was associated with an odds ratio (OR) of almost 2 for the occurrence of asymptomatic carotid atherosclerosis. The OR in men was 55% higher than in women. Individuals with diabetes had a >2-fold increased OR for asymptomatic carotid atherosclerosis. Increasing systolic blood pressure by 1 mm Hg resulted in a 3% higher risk for asymptomatic carotid atherosclerosis findings (hypertension OR=2.1; not shown). Compared with never smokers, former smokers had a 2-fold and current smokers had a 3-fold increased risk for presence of asymptomatic carotid atherosclerosis, following a significant trend. Subjects with no leisure time physical activity had a 1.9-fold increased risk for asymptomatic carotid atherosclerosis occurrence, which was borderline significant.
With the use of the second model, subjects with moderate lifestyle patterns had a 77% higher risk for asymptomatic carotid atherosclerosis than those with an optimal lifestyle pattern. In subjects with an unfavorable lifestyle pattern, the risk increase was even higher (OR=2.68), following a significant linear trend across categories.
SHIP is the first population-based general health survey in East Germany after German reunification. We found that a favorable lifestyle pattern based on leisure time physical activity and optimal dietary pattern may have a beneficial effect against atherosclerosis in never smokers. In contrast, even an optimal lifestyle pattern was not associated with a reduced level of atherosclerosis in smokers. Compared with surveys of other Western populations, this study revealed similar cardiovascular risk factors levels and mean CCA IMT values.13,14,23⇓⇓
Carotid IMT has been shown in prospective studies to be a predictor for incident myocardial infarction and stroke.11–14⇓⇓⇓ Furthermore, elevated plaque score, number of plaques, and degree of carotid artery stenosis were associated with higher risk of prevalent and/or incident coronary atherosclerosis,24–26⇓⇓ myocardial infarction,27,28⇓ or stroke.29–30⇓
West Pomerania is a region that is characterized by a higher incidence of death from stroke and myocardial infarctions than other parts of Germany.15
Studies relating physical activity to asymptomatic atherosclerosis revealed unequivocal results in the past. While data from the Atherosclerosis Risk in Communities (ARIC) Study suggested a beneficial relationship only for physical activity at work,31 the Tromsø Study revealed sex-dependent protective effects in men for leisure time physical activity as well.5,23⇓ The latter was mainly explained by the higher activity level among men.
In our study physical activity was borderline significantly related to subclinical atherosclerosis, whereas this relation was not significant in several other studies.6–8⇓⇓ However, clustering of different types of healthful behavior within an individual showed a significant beneficial effect on atherosclerosis in never smokers in the present study. Behavioral risk factors may act independently but also be influenced by other factors such as hypertension, HDL cholesterol, BMI, and diabetes.5,6⇓ In the present study an optimal lifestyle pattern was associated with a lower BMI, whereas systolic and diastolic arterial blood pressure as well as HDL and LDL cholesterol did not differ significantly in individuals with optimal and unfavorable lifestyle patterns. However, for the risk of subclinical carotid atherosclerosis, a significant linear trend across increasing dietary and lifestyle patterns categories remained statistically significant after we controlled for age, sex, hypertension, diabetes, alcohol intake, and smoking.
The present study has several strengths and weaknesses. We examined a large general population sample that included both sexes and covered a broad age range. Ultrasound measurements were performed by trained and certified technicians following a standardized protocol. Diet quality was assessed by a food frequency list, which has been shown as appropriate in several studies assessing the relationship between diet and disease.32 Although our food frequency list is rather short and not quantitative, the index allows differentiation into the categories of optimal, normal, and unfavorable. This could be shown in men aged 45 to 64 years when the index was compared with an equivalent index constructed from a 7-day food record.20 Our study is primarily limited by the cross-sectional study design, which did not allow us to establish a time sequence between the outcome examined (mean IMT, plaques, stenosis) and the lifestyle factors. Selective survival of those individuals whose arteries were less susceptible to unfavorable risk factor levels may have influenced the association among the elderly. In addition, the observed interaction between smoking status and other lifestyle factors should be confirmed prospectively. Another potential weakness is the restriction of quantitative IMT measurement to the CCA segment only; however, the latter is justified by the better reproducibility of measurements from this site and the difficulties in obtaining measurements from the bifurcation or the internal carotid artery.
In conclusion, former and present smoking was strongly associated with asymptomatic carotid atherosclerosis in this East German population. The smoking effect completely outweighed the beneficial effect of a favorable lifestyle, eg, leisure time physical activity and optimal dietary pattern, on asymptomatic atherosclerosis observed in never smokers. Thus, smoking avoidance and cessation are key factors in primary prevention campaigns enabling an individual to benefit from a further optimization of lifestyle factors. The behavior-dependent factors are potentially modifiable, indicating a cost-effective way of reducing subsequent cardiovascular and cerebrovascular events caused by increased atherosclerosis.
The SHIP study is part of the Community Medicine Net (http://www.medizin.uni-greifswald.de/cm) of the University of Greifs-wald, which is funded by grants from the German Federal Ministry of Education and Research (BMBF, grant 01ZZ96030), and of the Ministry for Education, Research, and Cultural Affairs and the Ministry for Social Affairs of the Federal State of Mecklenburg-West Pomerania. The contribution to the data collection made by the field workers, study physicians, ultrasound technicians, interviewers, and computer assistants is gratefully acknowledged.
- Received April 4, 2002.
- Revision received June 28, 2002.
- Accepted July 3, 2002.
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