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Journal of Clinical Epidemiology 53 (2000) 838–846

0895-4356/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S 0 8 9 5 - 4 3 5 6 ( 0 0 ) 0 0 1 9 8 - 0

Chin-Shan Community Cardiovascular Cohort in Taiwan–baseline data

and five-year follow-up morbidity and mortality

Yuan-Teh Lee

a,

*, Ruey S. Lin

b

, Fung C. Sung

b

, Chi-Yu Yang

a

, Kuo-Liong Chien

a

,

Wen-Jone Chen

a

, Ta-Chen Su

a

, Hsiu-Ching Hsu

a

, Yuh-Chen Huang

a

aDepartment of Internal Medicine, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei, Taiwan 100 bNational Taiwan University College of Public Health, Taipei, Taiwan

Received 27 October 1997; received in revised form 23 November 1999, accepted 10 January 2000

Abstract

A cohort consisting of 3602 residents (82.8% of the target population) aged 35 years and older was established in 1990 in the Chin-Shan Community, a suburb 20 miles outside of metropolitan Taipei, Taiwan. The long-term objective was to investigate the prospective impact on cardiovascular health in a society undergoing transition from a developing to a developed nation. This article presents the study design, selected baseline risk factors of cardiovascular diseases (CVD), and CVD events at the 5-year follow-up evaluation with an em-phasis on sociodemographic differences. The multivariate logistic regression analyses revealed that white-collar individuals were more likely than blue-collar workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL-C) levels ⬍35 mg/dl [odds ratio (OR) ⫽ 1.7, 95% confidence interval (CI) ⫽ 1.2–2.4] and low-density lipoprotein cholesterol (LDL-C) levels ⭓160 mg/dl (OR ⫽ 1.3, 95% CI ⫽ 1.0–1.7). However, they were at slightly lower risk for stroke and CVD/sudden death, and at moderately higher risk for coronary ar-tery disease and diabetes, although both these trends were not significant. Men were more likely than women to have HDL-C levels ⬍35 mg/dl (OR ⫽ 1.8, 95% CI ⫽ 1.4–2.2), but they were less likely to have LDL-C levels ⭓160 mg/dl (OR ⫽ 0.7, 95% CI ⫽ 0.6–0.8). The risk of CVD/sudden death was higher for men than for women during the follow-up period (OR ⫽ 1.9, 95% CI ⫽ 1.3–2.9). This could be due to risk factors such as a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%) use in men. In conclusion, in-dividuals of higher socioeconomic status have a higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD events. © 2000 Elsevier Science, Inc. All rights reserved.

Keywords: Cardiovascular disease; Dyslipidemia; Longitudinal study; Sociodemographic difference; Taiwan; Transitioning society

1. Introduction

Since the Framingham Study [1,2], considerable research efforts have been expended to conduct prospective studies investigating factors associated with the development of cardiovascular diseases (CVD). Such efforts have provided important information, increased the awareness of cardio-vascular risk factors, and helped to develop strategies for lipid, hypertension, and diabetes control, exercise, and smok-ing prevention [3–15]. It has been documented that mortality from strokes and ischemic or coronary heart disease has declined in developed Western countries since the mid-1960s [16]. However, few well-designed prospective stud-ies have examined risk factors for cardiovascular diseases in populations of developing and underdeveloped areas.

Beaglehole [17] named cardiovascular disease “a haunting epidemic” in developing countries ever since the World Health Organization encouraged CVD prevention in 1991 [18]. By the year 2000, cardiovascular disease will be the leading cause of death in many developing countries [19]. For example, mortality from ischemic heart disease doubled in Singapore from 1959 through 1983. Hughes [20] considered this increase to be the consequence of increasing wealth. Rapid economic development over the past few decades has caused Singapore to become the highest ranking nation in Asia in terms of per capita income, second only to Japan. Tai-wan, like many Asian countries, has seen a decline in deaths related to infectious diseases but has experienced a rapid in-crease in deaths resulting from chronic diseases, especially from cancer and cardiovascular diseases. Relative to the pop-ulations of Western countries, the Taiwanese population has a higher mortality rate from strokes and a lower death rate from coronary heart disease. Among CVD deaths in Taiwan (142 per 100,000 in 1990), 49.1% were from stroke, 39.4% from * Corresponding author. Tel.: 886-2-2356-2000; fax: 886-2-2321-7522.

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Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846 839 heart disease, and 11.4% from hypertensive disease [21]. The

risk of a stroke-associated death is four times higher in the Taiwanese population than in the American population [22].

Taiwan currently has the second highest population den-sity in the world and the third highest per capita income in Asia. According to recent projections, this island nation will soon be able to classify itself as a developed country [23]. It is interesting to study the trends in cardiovascular diseases as-sociated with this socioeconomic change, as well as to inves-tigate the multiple interrelated characteristics of lifestyle, se-lected biochemistries of blood and urine, imaging studies, and other physiological conditions in this transitional society. In 1990, a longitudinal study cohort was established in Chin-Shan, a suburban community 20 miles outside of Taipei, Taiwan. The primary objective of the Chin-Shan Community Cardiovascular Cohort (CCCC) Project was to measure the trends in and determinants of cardiovascular morbidity and mortality in a community that is experiencing rapid socioeconomic transition. The recent development of reliable blood chemistry analyses and ultrasonic imaging of heart and soft tissues has permitted the study team to initiate a thorough prospective investigation, identifying biochemi-cal and physiologibiochemi-cal factors for cardiovascular diseases in this population. This report describes the study design, dif-ferent findings by sociodemographic factors at baseline, and CVD events that occurred in the 5-year follow-up evaluation. 2. Methods

2.1. Study design and recruitment

Recruitment of study participants was initiated through extensive contacts with local population authorities to iden-tify households with individuals of eligible age, excluding those in institutions. About 36% of the population in the Chin-Shan area were aged 35 and above in 1990; this per-centage was reflective of the entire population in Taiwan. We contacted 4349 individuals of whom 747 (17.2%) did not respond, including 95 refusals and 652 individuals who

could not be reached due to working outside of the local

community. Of the 3602 (response rate 82.8%) individuals who participated in the baseline survey, 47.3% were men and 52.7% were women. Female participants were, on aver-age, younger and usually not employed outside the home (Table 1). The level of education reported by participants also demonstrated a typical characteristic of developing Asian countries: individuals, especially women, who had not received formal education, were usually senior citizens. Most participants belonged to families headed by blue-col-lar employees. A new cohort is being recruited every 5 years and included into the project in order to distinguish the possible cohort effect existing in the population. 2.2. Home visiting and baseline examination

A clinic was set up at the Chin-Shan Community Health Center (CCHC) by the study team, which consisted of 20

senior medical students, 2 assistant nurses, 10 cardiologists and local practitioners, and the officers of CCHC. Fourteen community leaders who were familiar with the families in the community also assisted with the identification and re-cruitment of potential participants. A letter describing the purpose and procedure of the study was delivered to each potential participant as an invitation to the clinic. For nonre-spondents, trained medical students were sent door-to-door, with the assistance of community leaders, to conduct a 2-h interview with each participant. These interviews collected baseline information such as demographic characteristics, lifestyle factors, dietary characteristics, and personal and family histories of diseases and hospitalization. With the consent of the participants, a physician and senior medical students conducted physical examinations and laboratory tests including electrocardiography, echocardiography, fun-doscopic examination, and sonographic measurement of ab-dominal subcutaneous fat. Achilles tendon thickness was also measured using ultrasonic images.

Various data collected from the interviews, physical ex-aminations, laboratory tests, and biochemical examinations are shown in Appendix 1. Urine and blood specimens were collected to determine levels of creatinine, uric acid, serum total cholesterol, serum triglycerides, low-density lipopro-tein cholesterol (LDL-C), high-density lipoprolipopro-tein choles-terol (HDL-C), lipoprotein(a), and apoliproproteins. Fasting blood samples for diabetes screening were also obtained from participants. Additionally, a 75-g oral dextrose test was given and glucose and insulin levels were determined 2 h after the glucose load [24]. Participants were later in-Table 1

Percentage distribution of demographic characteristics of participants by gender in the Chin-Shan Community Cardiovascular study at baseline Characteristics Male (n⫽ 1703) Female (n⫽ 1899) Ages 35–44 23.7 28.0 45–54 23.1 26.7 55–64 28.9 24.0 65–74 18.0 15.4 75⫹ 6.3 5.9 Married Yes 89.4 82.7 No 10.6 17.3 Occupation White collar 15.2 11.8 Blue collar 52.4 18.0 Other 2.3 2.4 None 30.1 67.5 Insurance Government 6.1 5.0 Labor/farmer/fisherman 83.2 79.9 Others 10.7 15.1 Education None 28.1 51.7 1–9 years 63.2 45.1 10–12 years 5.6 2.6 13⫹ years 3.1 0.6

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840 Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846 formed of their blood pressure and plasma lipid results.

Cal-ibration was conducted for every 20 specimens in the labo-ratory for blood and urine analyses. The methods of specimen and analyses are listed in Appendix 2. The results of the physical exams, laboratory tests, and imaging studies were reviewed independently by senior cardiologists.

Participants whose physical exams or laboratory test re-sults revealed abnormal findings were requested to have a second examination at the Chin-Shan Community Health Center or the National Taiwan University Hospital (NTUH). Those with elevated blood pressure, cholesterol, or other findings were advised to seek medical follow-up, which was provided by the CCHC, local practitioners, and NTUH on an as-needed basis. Interventions were also available to par-ticipants on a voluntary basis for hypertension control and lipid management [25].

2.3. Follow-up, study team, and diagnoses

The study team invited all participants to have biennial follow-up visits and examinations in 1992–93 and 1994–95 at the CCHC. The core personnel met every other week to discuss the field tasks being conducted, and medical stu-dents again participated in the study team as interviewers. Prior to joining the field tasks, all students were required to undergo a 2-week training course in internal medicine re-lated to this study at the Department of Internal Medicine,

NTUH. Techniques in measuring blood pressure, taking notes, interviewing, teaching, interpersonal skills, as well as some public health issues, were emphasized in the training course. During the survey period, staff and students usually held discussion sessions after home visits. The medical stu-dents were responsible for administering the questionnaire and interviewing participants. Information on general health, events of cardiovascular illness (hypertension, stroke, and coronary heart disease), and hospitalizations and anthropo-metric measurements were collected at this time.

Urine and blood specimens were requested again during the follow-up visits. In the first follow-up examination, measurements of apolipoprotein A1, apolipoprotein B, lipo-protein(a), and coagulation factors (including fibrinogen, plasminogen activator inhibitor, tissue plasminogen activa-tor, factor VII antigen, factor VII, and factor VIII) were

taken. All samples collected were stored at ⫺76⬚C using

liquid nitrogen if not shipped at 4⬚C to NTUH clinic

labora-tory within 8 h for analyses.

2.4. Monitoring morbidity and mortality

Events of selected CVDs (identified in the follow-up vis-its) and deaths (identified from the government vital regis-try) were reviewed by physicians on the Committee of Mor-tality and Morbidity within the study team. Medical records were used to determine the likely cause of death. Four cardi-ologists were responsible for reviewing the questionnaires, medical records, and laboratory reports to determine Table 2

Percentage distribution of lifestyle and baseline health status by gender in the Chin-Shan Community Cardiovascular study at baseline

Male (n⫽ 1703) Female (n⫽ 1899) Differencea (95% CI) Smoking: current 61.9 4.5 57.4 (54.9, 59.9) Alcohol: current 43.7 6.4 37.3 (34.7, 39.9) Betel nut: current 3.6 0.05 3.5 (2.2, 4.8) Tea: current 31.4 18.5 12.9 (10.1, 15.7) Coffee: current 6.9 8.8 ⫺1.9 (⫺0.1, ⫺3.7) Exercise or laborious job:

yes 69.4 49.3 20.1 (17.0, 23.2)

Body mass index, kg/m2

Mean ⫾ SD 23.0 ⫾ 3.3 24.6 ⫾ 5.7 ⫺1.6 (⫺1.8, ⫺1.4) 75th percentile 25.0 26.0

90th percentile 27.2 28.3

Diabetes mellitus: yes 8.5 8.6 ⫺0.1 (⫺1.9, 1.7)

CVA: yes 2.5 1.9 0.6 (⫺0.2, 1.4) CAD: yes 4.5 3.5 1.0 (⫺0.3, 2.3) Blood pressure (mmHg) Hypertension (Yes) Crude 25.7 30.8 ⫺5.1 (⫺8.0, ⫺2.2) Age-adjusted 25.0 32.0 ⫺7.0 (⫺10.0, ⫺4.0) Systolic ⭓140 Crude 19.7 25.7 ⫺6.0 (⫺8.7, ⫺3.3) Age-adjusted 18.9 26.9 ⫺8.0 (⫺10.7, ⫺5.2) Diastolic, ⭓90 Crude 14.1 15.5 ⫺1.4 (⫺0.9, 3.7) Age-adjusted 14.0 15.8 ⫺1.8 (⫺0.5, 5.1) All numbers are in percent except body mass index. CI: confidence in-terval; SD: standard deviation; CVA: cerebrovascular accident; CAD: cor-onary artery disease.

aMale-to-female difference.

Table 3

Means, standard deviations (in parentheses) for selected levels of lipid and other factors by gender in the Chin-Shan Community Cardiovascular study at baseline Factor Male (n⫽ 1703) Female (n⫽ 1899) Differencea (95% CI) Total cholesterol (mg/dl) 192.5 (44.7) 202.8 (45.8) ⫺10.3 (⫺13.3, ⫺7.3) Triglycerides (mg/dl) 128.5 (99.2) 123.4 (92.0) 6.3 (⫺0.2, 11.8) Lipoprotein cholesterol (mg/dl) HDL-C 46.3 (12.9) 48.5 (12.4) ⫺2.2 (⫺3.8, ⫺1.4) LDL-C 132.7 (43.3) 142.2 (44.5) ⫺9.5(⫺15.2, ⫺3.8) Lipoprotein(a) 14.0 (15.3) 14.5 (15.5) ⫺0.5 (⫺1.5, 0.5) HDL/LDL ratio 0.40 (0.2) 0.38 (0.2) 0.02 (0.01, 0.03) Uric acid (mg/dl) 6.4 (1.6) 5.0 (1.5) 1.4 (1.3, 1.5) Blood pressure (mmHg) Systolic 124.2 (19.4) 126.9 (21.8) ⫺2.7 (⫺4.1, ⫺1.3) Diastolic 77.0 (11.2) 77.3 (11.2) ⫺0.3 (⫺1.1, 0.4) Belly-skin-fold (mm) 12.0 (7.4) 17.6 (8.9) ⫺5.6 (⫺6.2, ⫺5.0) Left upper arm girth

(cm) 25.7 (5.1) 26.0 (4.1) ⫺0.3 (⫺0.5, ⫺0.1) Total protein (mg/dl) 7.72 (0.7) 7.84 (0.7) ⫺0.12 (⫺0.2, ⫺0.1) Albumin (mg/dl) 4.67 (0.5) 4.67 (0.6) 0.0 (⫺0.04, 0.04) Pre-albumin (mg/dl) 29.3 (9.8) 25.0 (6.4) 3.7 (3.2, 4.2) Trans-ferritin (mg/dl) 270.5 (51.4) 283.1 (52.7) ⫺12.6 (⫺16.1, ⫺9.1)

CI: confidence interval; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol.

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Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846 841 whether each event met the protocol established by the

project steering committee. Relatives of nonrespondents were contacted to obtain information on the health status of uncooperative individuals. Medical records were reviewed at CCHC, local clinics, and National Taiwan University Hospital. Using national vital statistics records, the study team was able to obtain information about deceased partici-pants and determine the attributed cause of death.

Diagnostic criteria for cardiovascular diseases and deaths were adapted from the recommendations of the New York Heart Association and the American Heart Association [26– 28]. Hypertension was diagnosed in individuals with sys-tolic blood pressure at or above 140 mmHg and/or diassys-tolic blood pressure at or above 90 mmHg, and in persons who were on antihypertension medications. Diabetes mellitus was diagnosed in those with fasting blood sugar levels higher than 140 mg/dl and in those with oral hypoglycemic agents or insulin treatment. Cerebrovascular disease was de-fined as a history of hemiparesis or hemiplegia confirmed by neurologists from NTUH by physical examination. Cor-onary heart disease was diagnosed by a history of myocar-dial infarction or electrocardiographic evidence of definite Q wave was found by the Minnesota Code [29].

2.5. Evaluation

For the baseline information reported in this article, we briefly described the study populations by gender, sociode-mographic characteristics, lifestyle, baseline health status, and lipid profiles using either mean differences or differ-ences in proportion to abnormal values. The 95% confi-dence intervals (CI) were provided for comparisons. An

in-dividual with a total cholesterol level ⭓240 mg/dl,

triglyceride level ⭓200 mg/dl, HDL-C ⬍35 mg/dl, LDL-C

⭓160 mg/dl, or lipoprotein(a) ⭓32.5 mg/dl was considered

to have dyslipidemia, in accordance with the Adult Treat-ment Panel II in the National Cholesterol Education Pro-gram (NCEP) of the U.S. [30]. Multivariable logistic regres-sion analyses were also used to measure the relative risk of

hypertension (yes vs. no), high LDL-C (⭓160 vs. ⬍160 mg/

dl), low HDL-C (⬍35 vs. ⭓35 mg/dl), and high TG (⭓200

vs. ⬍200 mg/dl). Odds ratios (OR) and 95% CIs were

esti-mated for different sociodemographic factors: gender, age, martial status, occupation, insurance status, and education level. In addition to reporting the incidence of selected CVDs and mortality from selected deaths in the follow-up period, logistic regression analyses were also used to mea-sure the risk of CAD, stroke, DM, and mortality from CVD/ sudden deaths for the above-mentioned sociodemographic factors.

3. Results

3.1. Baseline lifestyle and health status of study participants Cigarette, alcohol, and tea use was prevalent in male study participants (Table 2): 61.9% of males were current

smokers and 43.7% were regular users of alcohol. About 5% of female participants were smokers and 6% were alco-hol users. Women had a higher prevalence of hypertension

(32.0% vs. 25.0%; 95% CI of the difference ⫽ 4.0–10.0%)

and a higher average body mass index (24.6 vs. 23.0 kg/m2,

95% CI of the difference ⫽ 1.4–1.8 kg/m2) than men. The

prevalence of diabetes mellitus was similar between men and women; 8.5% for men and 8.6% for women. About 2.5% of the men had had a cerebrovascular accident (CVA) and 4.5% of the men had coronary artery disease (CAD). While both events were more prevalent in men than in women (1.9% and 3.5%, respectively), these differences were not statistically significant.

3.2. Blood biochemistries

Table 3 shows the average levels of lipid profiles and blood pressure. The average total cholesterol was signifi-cantly higher in women than in men (202.8 vs. 192.5 mg/dl;

95% CI of the difference ⫽ 7.3–13.3 mg/dl). Average levels

of both HDL-C (48.5 vs. 46.3 mg/dl; 95% CI of the

differ-ence ⫽ 1.4–3.8 mg/dl) and LDL-C (142.2 vs. 132.7 mg/dl;

95% CI of the difference ⫽ 3.8–15.2 mg/dl) were

cantly higher in women than in men. There was no signifi-cant difference between men and women in average level of lipoprotein(a). However, the average triglyceride level was higher in men than in women (128.5 vs. 123.4 mg/dl) at a borderline significance level. Average systolic blood pres-sure was also higher in women than in men (126.9 vs. 124.2

mmHg; 95% CI of the difference ⫽ 1.3–4.1 mmHg). Other

average measurements that were significantly greater in women than in men included average belly-skin fold (17.6 vs. 12.0 mm), left upper arm girth (26.0 vs. 25.7 mm), total protein (7.84 vs. 7.72 mg/dl), and trans-ferritin (283.1 vs. 270.5 mg/dl). Men had higher levels of pre-albumin than women (29.3 vs. 25.0 mg/dl).

Table 4 compares the percentage of individuals with ab-normal lipid profiles and other selected blood measure-ments between males and females. Calculation of crude and age-adjusted differences in the percentage of participants with dyslipidemia also revealed that the abnormalities were generally significantly more prevalent in women than in men in all categories. However, the largest gender differ-ence in lipoprotein cholesterol was observed in prevaldiffer-ence of low levels of HDL-C with an age-adjusted difference of 8.9%, higher in men than in women.

Logistic regression analyses were constructed to estimate the predictability of gender, age, marital status, occupation, education level, and health insurance status in hypertension and dyslipidemia at baseline (Table 5). White-collar indi-viduals, compared with blue-collar indiindi-viduals, were at ele-vated risk of having higher LDL-C and TG, and lower HDL-C, but not hypertension. Retired or unemployed indi-viduals showed a similar risk profile. This table also shows that compared with women, men were less likely to have a

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842 Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846

more likely to have a lower HDL-C level (OR ⫽ 1.8, 95%

CI ⫽ 1.4–2.2), and a higher TG level (OR ⫽ 1.2, 95% CI ⫽ 1.0–1.4).

3.3. Cardiovascular events found in the follow-up surveys The study team completed the first follow-up survey in September 1993 and the second follow-up survey in Octo-ber 1995 with a response rate of 88.7% among the 3368

sur-vivors in the 1995 survey (n ⫽ 2,988, 45.3% males and

54.7% females). Most of the nonrespondents (n ⫽ 380 or

11.3%) had either moved away or were unreachable. In these two follow-up surveys, 752 individuals with 969 new events of cardiovascular disease and 217 new cases of dia-betes were diagnosed (Table 6). As of February 1996, the

national vital statistics identified 369 deaths. Overall, men tended to have higher event rates than women in both mor-tality and incidence of diseases, except for strokes where men and women had similar incidence rates. Table 7 shows that men were more likely than women to have a higher rate

from CVD/sudden death (OR ⫽ 1.9, 95% CI ⫽ 1.3–2.9).

White-collar workers were less likely than blue-collar workers to have stroke or CVD/sudden deaths, but these dif-ferences were not statistically significant. White-collar workers also exhibited moderately elevated odds ratios for the incidence of CAD and DM, but this effect was not at a statistically significant level. Individuals with at least a pri-mary school education had higher incidence of DM than did individuals with no formal education.

4. Discussion

The baseline recruitment (82.8% response rate) and the follow-up (response rate 88.7%) were successful for at least two reasons: (a) the study team was able to organize an en-thusiastic group to make door-to-door visits to eligible indi-viduals’ participation, and (b) community leaders’ assis-tance in the project made participant recruitment much easier. In addition, community residents with higher aware-ness of individual health were pleased to receive a compre-hensive examination to look for precursors of cardiovascular events. The nonrespondents were mainly young individuals who worked outside the Chin-Shan area.

There are many population-based prospective studies in North America (e.g., Framingham, Bogalusa, Evans County, Stanford, Minnesota, ARIC, Honolulu, and Manitoba) and Europe [e.g., World Health Organization Monitoring and Cardiovascular (MONICA) Projects] [1–15,31–33]. While they have certainly provided important epidemiologic clues for understanding the pathophysiology of CVD, few studies have prospectively examined CVD in Asian populations. Al-though the MONICA Projects include Sino-MONICA and Japan-MONICA [33], the basic objective of MONICA is to measure a 10-year trend in cardiovascular mortality and morbidity and the associated population-based risk factors. The Taiwan CCCC study is unique because its objective is to observe the impacts of socioeconomic change on the devel-opment of CVD in a society in transition. In addition, this study was designed to add a new cohort to the study pool ev-ery 5 years. Newly eligible 35- to 39-year-old residents in Chin-Shan are being recruited into the study at 5-year inter-vals, allowing for future investigation of the cohort effect.

In addition, the CCCC study is distinct from other stud-ies because it primarily consists of blue-collar workers and includes a large number of housewives and other female participants. This population is representative of the general Taiwanese population, but has a lower overall education level than the urban population. This difference in education level may be linked to higher rates of risky behaviors such as smoking in men and higher fat consumption. Even if this is the case, it is still a valid goal to study dyslipidemia and Table 4

Crude and age-adjusted percent of study participants with dyslipidemia and elevated levels in other components by gender in the Chin-Shan Community Cardiovascular study at baseline

Factor Male (n ⫽ 1703) Female (n ⫽ 1899) Differencea (95% CI) Total cholesterol (⭓240 mg/dl) Crude 13.9 19.6 ⫺5.7 (⫺8.1, ⫺3.3) Adjusted 13.8 20.3 ⫺6.5 (⫺9.0, ⫺4.0) Triglycerides (⭓200 mg/dl) Crude 25.2 23.1 2.1 (0.7, 3.5) Adjusted 25.6 23.6 2.0 (0.6, 4.4) Lipoprotein cholesterol (mg/dl) HDL-C, ⬍35 Crude 21.8 13.6 8.2 (5.7, 10.7) Adjusted 22.9 14.0 8.9 (6.4, 11.4) LDL-C, ⭓160 Crude 23.3 28.4 ⫺5.1 (⫺8.9, ⫺2.3) Adjusted 23.1 31.3 ⫺8.2 (⫺11.1, ⫺5.3) Lipoprotein(a), ⭓32.5 Crude 9.5 12.2 ⫺2.7 (⫺4.7, ⫺0.7) Adjusted 9.5 12.3 ⫺2.8 (⫺4.8, ⫺0.8) HDL/LDL Ratio, ⬍0.20 Crude 10.0 8.6 1.4 (⫺0.5, 3.3) Adjusted 9.9 8.4 1.5 (⫺0.4, 3.4) Uric acid (⭓7.9 mg/dl) Crude 16.9 4.3 12.6 (10.6, 14.6) Adjusted 16.9 4.4 12.5 (10.5, 14.5) Total protein (⭓8.5 mg/dl) Crude 8.5 12.2 ⫺3.7 (⫺5.7, ⫺1.7) Adjusted 8.5 12.2 ⫺3.7 (⫺5.7, ⫺1.7) Albumin (⭓5.3 mg/dl) Crude 10.5 9.7 ⫺0.8 (⫺2.8, 1.2) Adjusted 10.7 9.8 ⫺0.9 (⫺2.9, 1.1) Pre-albumin (⭓36 mg/dl) Crude 16.3 5.0 11.3 (9.3, 13.3) Adjusted 16.6 5.1 11.5 (9.5, 13.5) Trans-ferritin (⭓341 mg/dl) Crude 7.6 11.9 ⫺4.3 (⫺5.3, ⫺3.3) Adjusted 7.7 11.5 ⫺3.8 (⫺4.8, ⫺2.8)

CI: confidence interval; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol.

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Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846 843

other factors associated with the development of hyperten-sion, ischemic heart disease, atherosclerosis, and other car-diovascular events. In planning this investigation, the study team observed that this target population is different from those of other studies. This population was in a higher risk group in terms of lipid profile according to the team’s his-torical experience in this area. On the other hand, the popu-lation in this community devotes a large amount of time to farming, fishing, and other labor-intensive occupations.

In two studies done in the rural village of San-Chih, Taipei County, the prevalence of hyperlipidemia (total

cho-lesterol level ⭓250 mg/dl) increased twofold from 5.5% in

1973 to 10.8% in 1991 [34,35]. A fivefold increase in CAD prevalence, from 0.6% to 3.1%, was reported during the same time period. Chin-Shan is a more urban community than San-Chih; the Chin-Shan study cohort had a preva-lence rate of 16.9% for hyperlipidemia (total cholesterol

⭓240 mg/dl) and a prevalence rate of 4.1% for CAD. As

Taiwan makes its transition to a developed nation, the per capita daily energy consumption from fat has increased from 22% in 1971 to 28% in 1981, 37% in 1991, and 40% in 1995 [36]. As fat consumption continues to increase in Taiwan, we predict that the prevalence of dyslipidemia will also increase, particularly among uninformed populations.

Similar to blood lipid levels, smoking levels among partici-pants of the CCCC study were consistent with those of the general population of Taiwan as reported by other cross-sec-tional studies [37–40]. The prevalence rate of smoking in

Chin-Shan was lower than the rates in areas of mainland China such as Beijing and Quangzhou (71% and 78% for men and 3.2% and 31% for women, respectively). But the preva-lence of abnormal total cholesterol was much lower for people in Beijing and Quangzhou (about 175 mg/dl on average) [41]. The average blood cholesterol level for this study cohort may be comparable with that of the U.S. population [6,7,41]. In ad-dition, the prevalence of hypertension for men in the CCCC project was similar to that found in a study conducted in the U.S. [42]. CCCC women, though, were found to have a higher prevalence of hypertension than U.S. women [42]. Further-Table 5

Odds ratios of hypertension and dyslipidemia by sociodemographic factors in the Chin-Shan Community Cardiovascular study at baseline Hypertension OR (95% CI) LDL-C OR (95% CI) HDL-C OR (95% CI) TG OR (95% CI) Gender Male 0.96 (0.8–1.2) 0.7 (0.6–0.8) 1.8 (1.4–2.2) 1.2 (1.0–1.4) Female 1.0 1.0 1.0 1.0 Age 35–54 1.0 1.0 1.0 1.0 55–64 2.0 (1.5–2.5) 1.9 (1.6–2.3) 1.4 (1.1–1.8) 1.2 (1.0–1.4) 65⫹ 2.5 (1.9–3.3) 1.8 (1.5–2.3) 1.4 (1.0–1.8) 1.1 (0.9–1.4) Married No 1.0 1.0 1.0 1.0 Yes 1.0 (0.6–1.6) 1.3 (0.8–2.0) 0.7 (0.4–1.2) 1.6 (1.0–2.7) Occupation Blue collar 1.0 1.0 1.0 1.0 White collar 1.1 (0.8–1.5) 1.3 (1.0–1.7) 1.7 (1.2–2.4) 1.4 (1.1–1.9) Othersa 1.1 (0.9–1.5) 1.2 (1.0–1.5) 1.4 (1.1–1.9) 1.4 (1.1–1.7) School Education None 1.0 1.0 1.0 1.0 Yes 1.1 (0.9–1.4) 1.1 (0.9–1.3) 1.1 (0.9–1.4) 1.2 (1.0–1.5) Insurance Government 1.0 1.0 1.0 1.0 Laborb 1.1 (0.7–1.8) 0.9 (0.7–1.3) 0.9 (0.6–1.4) 0.9 (0.7–1.3) Other 1.2 (0.7–2.0) 0.9 (0.7–1.4) 1.2 (0.8–1.9) 1.0 (0.7–1.5)

LDL-C: low-density lipoprotein cholesterol ⭓ 160 mg/dl; HDL-C: high-density lipoprotein cholesterol ⬍ 35 mg/dl; TG: triglycerides ⭓ 200 mg/dl; OR: odds ratio; CI: confidence interval.

aRetired and unemployed.

bLabor insurance covered also farmers and fishermen.

Table 6

Incidence cases and rates (per 1000 person-years) of cardiovascular diseases, diabetes mellitus, and death identified in the follow-up surveys, Chin-Shan Community Cardiovascular study

Events Male No. (rate) Female No. (rate) Male-to-Female RR (95% CI) Disease CAD 51 (8.7) 48 (7.2) 1.21 (0.82–1.79) Hypertension 290 (49.2) 289 (43.4) 1.13 (0.96–1.33) Stroke 35 (5.9) 39 (5.9) 1.00 (0.63–1.58) Diabetes 112 (19.0) 105 (15.8) 1.20 (1.08–3.57) Death CVD/sudden death 67 (7.0) 42 (5.3) 1.32 (0.90–1.94) Cancer 72 (7.5) 38 (4.8) 1.56 (1.07–2.35) Others 90 (9.4) 60 (7.5) 1.25 (0.90–1.73)

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844 Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846

more, smoking rates among men in Chin-Shan and Taiwan were more than double the rate of American men, although smoking rates were much lower among Taiwanese women than among American women [43,44]. Smoking cigarettes, particularly American cigarettes, has become fashionable for men in Taiwan and has increased from 40% in 1987 to the current rate of 60% [31,43]. Smoking has traditionally been considered inappropriate behavior for women in Taiwan, which accounts for the low smoking rate among women.

Some of the interesting findings revealed by the baseline information and lipid results were that although white-collar individuals had an elevated risk of having dyslipidemia (Table 5), with insignificantly elevated risk of diabetes and death from CAD (Table 7), they were not at an elevated risk of stroke or CVD/sudden death. This phenomenon suggests no strong evidence of a relationship between dyslipidemia and the likelihood of CVD events among social classes in this community cohort. Individuals with at least a primary school education are slightly less likely to hold blue-collar jobs and also have a slightly increased likelihood of having dyslipi-demia because they are more affluent and presumably con-sume more calories from fat. White-collar individuals in gen-eral have received a school education and have better access to health care. These factors lead to a small and insignificant re-duction from stroke and CVD/sudden death. On the other hand, they may have a higher risk of diabetes and death from CAD, although this finding was also not statistically

signifi-cant. Thus, the sociodemographic status in this cohort may have a significant association with the risk of dyslipidemia, but this effect is not strong enough to alter the overall risk of cardiovascular events. As the majority of the study population received no more than 9 years of education, the overall aware-ness of cardiovascular disease prevention may be low, yet at the same time this cohort is at risk for developing dyslipi-demic because of improved economic status in recent years.

Although women in this study were generally younger than men, they were more likely than men to have hyperlipidemia. Similarly, hypertension was more prevalent in women, al-though they had lower prevalence rates of CVA and CAD than in men at baseline. Women also had a lower incidence of hypertension and CAD than men in the follow-up years. How-ever, multivariate logistic regression analysis for the follow-up surveys revealed that men were 1.9 times more likely than women to have CVD/sudden death. We found that

hyperten-sion was the most important risk factor (risk ratio, RR ⫽ 5.20,

95% CI ⫽ 3.16, 8.58; data not shown), followed by smoking

status (RR ⫽ 2.34, 95% CI ⫽ 1.23, 4.46) and lower levels of

HDL-C (RR ⫽ 1.59, 95% CI ⫽ 1.0, 2.55). Because the

smok-ing rate was as high as 62% in men, it is possible that patients with CVD have followed their physicians’ suggestions to quit smoking but that they did not quit soon enough.

Based on the Chin-Shan baseline data, the population in Taiwan is at a higher risk than ever for CVD. Without modifi-cations in dietary behavior and lifestyle, the incidence of CVD Table 7

The estimated relative risk of CAD, stroke, and DM incidence, and CVD/sudden death at follow-up evaluation by baseline sociodemographic factor, Chin-Shan Community Cardiovascular study

CAD OR (95% C.I.) Stroke OR (95% C.I.) CVD/sudden death OR (95% C.I.) DM OR (95% C.I.) Gender Male 1.1 (0.8–1.6) 1.1 (0.6–1.8) 1.9 (1.3–2.9) 1.3 (0.9–1.8) Female 1.0 1.0 1.0 1.0 Age 35–54 1.0 1.0 1.0 1.0 55–64 2.4 (1.5–3.7) 2.4 (1.2–4.9) 2.5 (1.2–5.0) 1.6 (1.2–2.3) 65⫹ 2.7 (1.6–4.4) 4.9 (2.3–10.2) 11.3 (5.9–21.7) 1.4 (0.9–2.3) Married No 1.0 1.0 1.0 1.0 Yes 0.9 (0.4–2.4) 0.5 (0.2–1.3) 2.6 (0.8–8.5) 0.9 (0.4–2.0) Occupation Blue collar 1.0 1.0 1.0 1.0 White collar 1.5 (0.9–2.7) 0.8 (0.3–2.5) 0.8 (0.3–2.0) 1.4 (0.9–2.3) Othersa 1.0 (0.7–1.7) 1.2 (0.6–2.3) 1.2 (0.7–2.0) 1.5 (1.0–2.2) School Education None 1.0 1.0 1.0 1.0 Yesb 0.8 (0.6–1.2) 0.6 (0.4–1.1) 0.8 (0.5–1.2) 1.3 (1.0–1.9) Insurance Government 1.0 1.0 1.0 1.0 Laborc 1.1 (0.5–2.2) 1.3 (0.4–3.6) 0.6 (0.3–1.1) 0.9 (0.5–1.5) Other 1.0 (0.5–2.3) 1.1 (0.3–3.4) 0.6 (0.3–1.3) 1.2 (0.6–2.3)

CAD: coronary artery disease; DM: diabetes mellitus; OR: odds ratio; CI: confidence interval.

aRetired and unemployed. bSix years and above.

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Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846 845 will remain at a peak level [21]. However, it is also important

to identify the difference between men and women for inci-dence of dyslipidemia and CVD and deaths from cardiovascu-lar events. The longitudinal nature of the CCCC project en-hances its ability to identify risk factors for CVD. Further analyses will emphasize the secular changes in lipid profiles and other biomarkers from baseline to follow-up surveys, strat-ified by sociodemographic factors, and will investigate their associations with the development of new CVD cases and

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Acknowledgments

This study was supported by research grants (DOH-79-06, 80-30, 81-27, 82-TD-86, and DOH83-TD-95) from the Department of Health, Taiwan, Republic of China.

Appendix 1

Elements of baseline survey and examination in the Chin-Shan Community Cardiovascular study

Demographic variables Sex, birth date, ethnicity, education, marital status, religion, insurance, occupation Lifestyle factors Smoking, alcohol, tea/coffee, betel nut, exercise, stress

Personal/family health history Hypertension, diabetes, stroke, CAD, heart disease, arrhythmia, rheumatism, lipidemia, etc. Blood pressure/anthropometry Weight, height, skinfold, bellyfold, etc.

Physical examination Heart, lung, extremities, spine, arcus senilis xanthelasma/xanthoma, other chest/heart/cardiovascular exams Ultrasound/electrocardiogram 2-Dimensional, M-mode measurement, Color and Doppler mapping, echocardiography

Eye fundography Macular, eye ground, vessels characteristics

Blood/urine chemistry Lipid profilesa, uric acid, blood urea nitrogen, creatinine, pre-albumin, blood cell count, sugar, electrolytes. aTotal cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, lipoprotein(a), lipoprotein, apolipoprotein A1, apolipoprotein B, and

coagulation factors.

Appendix 2

Laboratory measurements and methods used in the Chin-Shan Community Cardiovascular study

Specimen Measurement Method Blood Total cholesterol Enzymatic [45]

Lipoprotein phenotyping Precipitation [46, 47] Total triglycerides Enzymatic [48] Blood count Counter [49]

Electrolytes ISE (ion-selective-electrode) [50] Proteins Biuret [51]

Apolipoproteins Turbitimetric immunoassay [52] Lipoprotein(a) ELISA [53]

Glucose Enzymatic [54]

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846 Y.-T. Lee et al. / Journal of Clinical Epidemiology 53 (2000) 838–846 Prognosis and Risk Assessment in Cardiovascular Disease. New

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