Stroke is the fourth leading cause of death in the world.1 This is of particular concern in China, where stroke accounts
for ≈20% of all causes of death.2 Based on a recent estimation, >7 million Chinese experience stroke, and 2 million individu-als are newly diagnosed each year.2 Developing efficient pre-ventive approaches is considered the most effective strategy to minimize the stroke-related health burden among the gen-eral population.3 Recently, the American Heart Association developed the concept of ideal cardiovascular health (CVH), which is defined as the simultaneous presence of 4 ideal health behaviors (nonsmoking, body mass index [BMI] <25 kg/m2, physical activity at goal levels, and a diet consistent with cur-rent guideline recommendations) and of 3 ideal health factors (untreated total cholesterol <200 mg/dL, untreated systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg, and untreated fasting blood glucose <100 mg/dL).4
This primordial prevention, distinctly different from primary prevention, focuses on preventing the initial occurrence of risk factors by adopting healthier behaviors rather than preventing the development of a given disease.5 Previous studies showed a low prevalence of these ideal CVH metrics in the general population of the United States and a strong inverse relation-ship between the number of ideal CVH metrics and the total incidence of cardiovascular diseases and stroke.6–9 One of our studies showed a similar association with the total car-diovascular disease risk in a Chinese population.10 However, few studies have examined the impact of ideal CVH metrics on the risks of ischemic and hemorrhagic stroke, respectively, which have different etiologies and risk factors. We, therefore, performed a prospective study to examine whether ideal CVH parameters were associated with a lower risk of stroke (total, ischemic, and hemorrhagic).
Background and Purpose—Previous studies showed an inverse association between ideal cardiovascular health (CVH) metrics and the total risk of cardiovascular diseases and stroke. This study aimed to investigate the relationship between ideal CVH metrics and the risks of ischemic and hemorrhagic stroke, respectively.
Methods—We collected information on the 7 ideal CVH metrics (including smoking status, body mass index, dietary intake, physical activity, blood pressure, total cholesterol, and fasting blood glucose) among 91 698 participants from the Kailuan study, China (72 826 men and 18 872 women between the ages of 18 and 98 years), free of myocardial infarction and stroke at baseline (2006–2007). Cox proportional hazards models were used to estimate stroke risk.
Results—During the 4-year follow-up, we identified 1486 incident stroke events (1057 ischemic, 386 intracerebral hemorrhagic, and 43 subarachnoid hemorrhagic). The hazard ratios (95% confidence interval) for total stroke with adherence to 0 (reference), 1, 2, 3, 4, 5, and 6/7 ideal CVH metrics were: 1, 0.92 (0.69–1.23), 0.69 (0.52–0.92), 0.52 (0.39–0.68), 0.38 (0.28–0.51), 0.27 (0.18–0.40), and 0.24 (0.11–0.54), respectively (P trend <0.01), after adjusting for age, sex, education, income, and hospital. Similar inverse associations were observed for both ischemic and intracerebral hemorrhagic stroke (both P trend <0.01).
Conclusions—We observed a clear inverse gradient relationship between the number of ideal CVH metrics and the risk of stroke in a Chinese population, supporting the importance of ideal health behaviors and factors in stroke prevention. (Stroke. 2013;44:2451-2456.)
Key Words: cardiovascular health ◼ epidemiology ◼ prevention & control ◼ stroke
Ideal Cardiovascular Health Metrics and the Risks of Ischemic and Intracerebral Hemorrhagic Stroke
Received September 30, 2012; final revision received May 18, 2012; accepted May 24, 2013.From the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (Q.Z., Y.Z., C.W., S.Z., A.W., N.L., L.B.,
J.W., Q.J., X.Z.); Department of Cell Transplantation, the General Hospital of Chinese People’s Armed Police Forces, Beijing, China (Q.Z.); Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA (X.G.); Department of Nutrition, Harvard University School of Public Health, Boston, MA (X.G.); Department of Neurology, the General Hospital of Chinese People’s Armed Police Forces, Beijing, China (S.Z.); and Department of Cardiology, Kailuan Hospital, Tangshan, China (S.W.).
*Drs Zhang and Zhou contributed equally.The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
113.678839/-/DC1.Correspondence to Xingquan Zhao, MD, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. E-mail
Materials and MethodsStudy Design and PopulationThe Kailuan study10 is a prospective cohort study based on the Kailuan community, in Tangshan city, a large modern city Southeast of Beijing. From June 2006 to October 2007, all 155 418 employ-ees, ≥18 years of age (including the retired) of the Kailuan Group, were invited to participate. Among them, 65.3% agreed and provided written informed consent. The mean age of cohort participants was comparable to that of the whole population of employees (51.93 years in the current cohort versus 51.92 years in the company), but there is a significant difference in sex distribution (79.9% men ver-sus 85.9%). A total of 101 510 participants (81 110 men and 20 400 women, 18–98 years of age) were recruited in the Kailuan study. All participants underwent questionnaire assessments and clinical and laboratory examinations conducted in the 11 hospitals responsible for healthcare of this community. Ongoing evaluations included bi-ennial measurements of the above parameters and annual recording of adverse events. In this study, we excluded 3669 participants who had a history of myocardial infarction or stroke at baseline, and 6143 participants who had incomplete data on health factors or behav-iors, leaving 72 826 men and 18 872 women (Figure) available for analyses. The study was performed according to the guidelines of the Helsinki Declaration and was approved by the Ethics Committee of the Kailuan General Hospital, the Beijing Chaoyang Hospital, and the Beijing Tiantan Hospital.
Assessment of Cardiovascular Health Metrics and Potential Covariates at BaselineData on smoking, dietary salt intake, and physical activity were col-lected using questionnaires. Ideal smoking status was defined as hav-ing never smoked. Ideal dietary data, mainly based on salt intake, were defined as a consumption of <6 g/d. Ideal physical activity was defined as moderate or vigorous physical activity for >80 minutes per week.
Weight and height were measured and BMI was calculated as weight(kg)/height(m)2. BMI was defined as ideal if it was <25 kg/m2.
Systolic blood pressure and diastolic blood pressure were measured twice in the seated position using a mercury sphygmomanometer. The average of the 2 readings was used for the analyses. Blood pressure was defined as ideal if systolic blood pressure was <120 mm Hg and diastolic blood pressure was <80 mm Hg, without antihypertensives.
Blood samples were collected from the antecubital vein after an overnight fast. All blood samples were tested using a Hitachi 747 auto-analyzer (Hitachi; Tokyo, Japan) at the central laboratory of the Kailuan General Hospital. Fasting blood glucose was defined as ideal if <100 mg/dL and if untreated. Total cholesterol was defined as ideal if the untreated total cholesterol level was <200 mg/dL. Otherwise, they were defined as nonideal.
Data on demographic variables (eg, age, sex, household income, and education) were collected using questionnaires.
Follow-up and Stroke AssessmentParticipants were followed up by face-to-face interviews at every 2-year routine medical examination until December 31, 2010, or to the event of interest or death. The follow-ups were performed by trained physicians who were blinded to the baseline data. The outcome infor-mation was further confirmed by checking discharge summaries from the 11 hospitals, and medical records from medical insurance. For the participants without face-to-face follow-up, the outcome information was obtained directly by checking death certificates from provincial vital statistics offices, discharge summaries, and medical records. We documented 1564 deaths during the follow-up.
The primary outcome was the first occurrence of stroke, either the first nonfatal stroke event, or stroke death without a preceding nonfatal event. A nonfatal stroke was defined as the sudden onset of a focal neurological deficit with a vascular mechanism lasting >24 hours. Cases of fatal stroke were documented by the evidence of a cerebrovascular mechanism. Stroke was diagnosed according to the World Health Organization criteria11 combined with a brain computed tomography (CT) or magnetic resonance (MR) for confirmation, and classified into 3 main types: cerebral infarction, intracerebral hemor-rhage, and subarachnoid hemorrhage. The criteria were consistently applied across all participating hospitals. All stroke outcomes were
Figure. Flowchart of the study. MI indicates myo-cardial infarction.
Zhang et al Ideal Cardiovascular Health Metrics and Stroke 2453
validated by the Data Safety Monitoring Board and the Arbitration Committee for Clinical Outcomes. Considering the small sample size (n=43) and different pathogenesis, we did not include the subarach-noid hemorrhage group in this study.
Statistical AnalysesStatistical analyses were performed using SAS 9.3 (SAS Institute; Cary, NC). Continuous variables were compared using ANOVA analyses, and categorical variables were compared using χ2 tests. Participants contributed person-time of follow-up from the date of return of the baseline questionnaire to either the date of stroke onset, death, or end of follow-up (December 31, 2010). Cox proportional hazards regression was used to estimate the stroke risk by calculating the hazard ratios and 95% confidence intervals because there was no evidence of nonproportional hazards for exposures (P=0.97). Because only a few participants had 7 ideal CVH metrics, we combined them with participants who had 6 ideal metrics. Because there were 11 hos-pitals participating in the study, we used the Cox proportional hazard model with a sandwich covariance matrix as a random effect to ac-count for the potential confounding effect because of different hos-pitals. We adjusted hazard ratios models for age, sex, education, and income because they are known risk factors for stroke,12 and were as-sociated with the exposure. We also adjusted for the other 6 metrics in the analyses of each individual CVH component because they may not be independent from each other. For testing the trends, we assigned a numeric value to the number of ideal CVH metrics and analyzed it as a continuous variable. Because the relationship between the number of CVH metrics and the risk of stroke may not be linear, we introduced quadratic terms and natural logs of the CVH metrics number into the models, and the quadratic and natural log terms were not statistically significant (P>0.10 for all). We, therefore, used simpler models with original scales for CVH metrics number. We tested interactions with age (<60 years versus ≥60 years) and sex. All statistical tests were 2-sided, and a significant level was set as 0.05.
ResultsDuring the 4-year follow-up, we identified 1057 incident isch-emic, 386 intracerebral hemorrhagic, and 43 subarachnoid hemorrhagic stroke cases.
Participants with a greater number of ideal CVH metrics were more likely to be women, young people, and had higher education and income (Table 1).
We observed significant associations between the presence of each ideal CVH component and lower risks for total and ischemic stroke (P<0.05 for all; Table 2). Except for total cholesterol, similar inverse trends were observed for intrace-rebral hemorrhagic stroke. However, only ideal blood pressure reached a significant level (P<0.01).
Participants with more ideal CVH metrics had a lower cumulative incidence of stroke (Table 3). An association between the number of ideal CVH metrics and the lower risk for total stroke remained significant after adjusting for age, sex, and other covariates (P trend <0.01). Significant inverse associations were observed in both ischemic and intracerebral hemorrhagic stroke (P trend <0.01 for both).
We did not observe a significant interaction between the number of ideal health metrics and age or sex in relation to stroke risk (P>0.10 for both interactions), after adjusting for potential covariates.
DiscussionIn this large-scale Chinese cohort, we found that individu-als who met 6 or 7 ideal CVH metrics were 76% less likely to develop stroke during a 4-year follow-up, compared with those who did not meet any of the 7 metrics. Our study dem-onstrated for the first time the potential combined protective impact of the American Heart Association defined ideal CVH metrics on ischemic and intracerebral hemorrhagic stroke.
To the best of our knowledge, only 1 study reported the rela-tionship between ideal CVH metrics and stroke, as part of an analysis on total cardiovascular diseases. In this study on 2981 participants from the Northern Manhattan study, Dong et al8 observed an inverse relationship between the number of ideal
Table 1. Participants’ Characteristics According to the Number of Ideal Cardiovascular Health Metrics at Baseline (2006–2007)
CVH metrics and the risk of total stroke in whites, blacks, and Caribbean Hispanics. However, this study was limited by its small sample size and failed to examine the potential effects of CVH metrics on ischemic and hemorrhagic stroke, respectively.
Our findings are consistent with previous studies showing the combined effect of several healthy lifestyle factors associ-ated with stroke risk. In a study on the basis of 114 928 par-ticipants from the Health Professionals Follow-up study and the Nurses’ Health study, 2553 strokes (1453 ischemic and 439 hemorrhagic) were identified during follow-up. Individuals with a healthy lifestyle pattern (defined as nonsmoking, BMI <25 kg/m2, ≥30 minutes/d of moderate activity, moderate alco-hol consumption, and a favorable overall diet quality) had an 80% lower risk of developing stroke compared with those who had none of the above factors.13 In another study comprising 36 686 Finnish participants, in which 1167 ischemic and 311
hemorrhagic strokes were confirmed, an inverse association was observed between the number of healthy lifestyle indica-tors (including smoking, BMI, physical activity, and consump-tions of vegetables and alcohol) and the risks of total stroke and its 2 major subtypes (ischemic and hemorrhagic stroke).14 However, in the Women’s Health study, a lifestyle score based on the 5 similar lifestyle factors as described above was found to be inversely associated with the risks of total (450 incident cases) and ischemic stroke (356 cases), rather than hemor-rhagic stroke (90 cases).15 Our results on the stroke subtype pattern were also consistent with previous studies performed in Asia, showing a higher proportion of hemorrhagic stroke (20% to 30% of total stroke)16 than that in the Western populations.
We also examined the associations between each individual health metric and stroke risk. Although ischemic stroke and intracerebral hemorrhagic stroke share some common risk
Table 2. Hazard Ratios (HRs) of Ideal to Nonideal Group of Each Cardiovascular Health Metric for Stroke
BMI indicates body mass index; and CI, confidence interval.*Incidence rate per 1000 person-years.†Adjusted for age (year), sex, hospital, education, income, and the other 6 health metrics.
Zhang et al Ideal Cardiovascular Health Metrics and Stroke 2455
factors, such as hypertension, effects of other risk factors are different. Consistent with previous studies,12,14,17–20 our study showed significant associations between each ideal health behavior/factor and the risks of total and ischemic stroke. We did not find a significant relationship between health behav-iors and intracerebral hemorrhagic stroke. As for health fac-tors, only ideal blood pressure was found to be significantly inversely associated with the risk of intracerebral hemorrhagic stroke, consistent with previous studies that showed hyperten-sion was the most important single risk factor for intracerebral hemorrhage.21,22 The effect sizes of the association were simi-lar to what we observed for ischemic stroke (adjusted hazard ratios were 0.51 for ischemic stroke and 0.39 for intracerebral hemorrhagic stroke; P>0.05 based on their 95% confidence intervals). Possible reasons for the different results between ischemic and intracerebral hemorrhagic stroke lie in the dif-ferent pathogenesis. Furthermore, because of relatively lower incidence, fewer hemorrhagic stroke cases were included in our study, as well as in previous studies, precluding the associ-ation from reaching a significant level. For example, although the ideal physical activity status had similar magnitude of effect on the risk of developing intracerebral hemorrhagic and ischemic stroke (19% versus 24% lower risk, respectively), the association was only significant for ischemic stroke but not for intracerebral hemorrhagic stroke. Thus, a larger sam-ple size or a longer follow-up period is needed to understand potential risk factors for hemorrhagic stroke. It is worth not-ing that being overweight could be a consequence of several known risk factors for stroke (eg, unhealthy lifestyle) and may be affected by other factors, such as occult malignancy.
However, we did observe that being overweight had deleteri-ous effects on stroke risk after adjusting for other risk factors, consistent with the results reported in the Physicians’ Health study23 and in a recent meta-analysis.24
Our results suggest that health behaviors and factors play an important role in the prevention of stroke. All participants are employees (including the retired) of the Kailuan Group. Although it is possible that some participants may move to other communities during follow-up, the impact because of loss-to-follow-up could be modest because all participants’ health insurance has been covered by the Kailuan Medical Group. However, some limitations need to be considered. First, the Kailuan study is not a nationwide study. Specifically, as an industrial city, a large proportion of participants are manual workers, including coalminers. Our findings may therefore not be directly generalized to other Chinese populations. We cannot totally exclude the possibility of selection bias in that relatively healthy individuals may be more likely to refuse to participate in the free medication examination. Second, we did not use validated dietary and physical activity questionnaires. Given that salt intake was consistently found to be associated with risk of stroke in previous epidemiological studies25,26 and salted food intake is a serious situation in China,27 we used salt intake as a surrogate of diet quality. However, we are aware that salt intake could only reflect 1 aspect of overall dietary pat-tern, and other aspects, such as consumption of fat, and fruit/vegetables are also important for stroke pathogenesis. Our results, therefore, should be interpreted with caution. Third, we just added the number of ideal metrics together and explored the overall trend. The CVH metrics may not be independent
Table 3. Hazard Ratios (HRs) for Stroke According to the Number of Ideal Cardiovascular Health Metrics
Characteristic
Number of Ideal Cardiovascular Health Metrics P Value Trend0 1 2 3 4 5 6&7
from each other and we did not consider that the weight of different metrics may have different impacts. However, this calculation method has been used in several published studies, such as Dong8 and Folsom,6 to obtain the approximate relation-ship between health metrics and outcome events. Furthermore, the number of participants who had 6 or 7 ideal CVH metrics and the number of participants with hemorrhagic stroke were small, which may reduce the statistical power to detect the true relationship. Nevertheless, the small number of stroke patients with 6 or 7 ideal health metrics did not preclude us to detect a significant association, but the association might have been stronger or more stable if we had a larger proportion of par-ticipants in this group. Finally, because of a lack of detailed imaging information, cerebral vascular and cardiac evaluation in some stroke cases, we were unable to further explore the relationship between ideal CVH metrics and different subtypes of ischemic stroke. We also did not explore the effect of treat-ments for nonideal metrics on stroke outcomes, such as hyper-tension. Further studies with a larger sample size are needed to confirm our results.
ConclusionsWe observed a clear inverse gradient relationship between the number of ideal CVH metrics and the risk of stroke (ischemic and intracerebral hemorrhagic). Our findings provide direct evidence for the importance of ideal health behaviors and fac-tors in stroke prevention.
AcknowledgmentsWe thank all enrolled participants and their relatives.
Sources of FundingThis study was performed as a collaborative study supported by the Ministry of Science and Technology and by the Ministry of Health of the People’s Republic of China (2008BAI52B03).
DisclosuresNone.
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Supplemental table Ⅲ: Baseline characteristics among different genders
BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG: fasting blood glucose; TC: total cholesterol *average monthly income of every family member
Total (n=91,698) Female (n=18,872) Male (n=72,826) p
IS: ischemic stroke; ICH: intracerebral hemorrhagic stroke; *: Adjusted for age (year), sex, education, average monthly income of every family member, and hospital.
Supplemental tableⅤ: Hazard Ratios (HRs) for Stroke According to the Number of Ideal Cardiovascular Health Metrics, stratified by genders
Number of ideal cardiovascular health metrics 0 1 2 3 4 5 6&7 P trend Men Participants (n) 2269 9661 19707 22645 14203 3792 549 Total stroke
IS: ischemic stroke; ICH: intracerebral hemorrhagic stroke; *: Adjusted for age (year), education, average monthly income of every family member, and hospital. †: Participants with adherence to 0/1 ideal CVH metric were used as the reference group.
