Short-term intraindividual variability in lipoprotein measurements: the Atherosclerosis Risk in Communities (ARIC) Study.

Much epidemiologic research is based on estimation of an association between a putative risk factor and a health outcome--for example, plasma concentration of lipoproteins and ischemic heart disease. Since the repeatability of a risk factor measurement determines, in part, the ability to ascertain its association in populations, the Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability Study was conducted to estimate various components of variation in analyte data and to estimate the repeatability of these measurements. A total of 40 subjects (17 males and 23 females) from Forsyth County, North Carolina, Minneapolis, Minnesota, Jackson, Mississippi, and Washington County, Maryland, were studied in 1988. Fasting blood was collected three times from each subject, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person variability, and processing and assay variability were estimated. From these components, the reliability coefficient, R, the correlation between measures made at repeat visits, was estimated. R was above 0.85 for total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and lipoprotein(a). Low repeatability was obtained for apolipoprotein A-I (R = 0.60). High density lipoprotein subfractions 2 and 3 were intermediate in repeatability. Reliability coefficients from the ARIC Intraindividual Variability Study are generally higher than those found in other studies, and this is related to relative variability in populations studied, to the time between measurements, and to differences in laboratory variability. Only for apolipoprotein A-I would the findings strongly suggest the need to adjust for measurement variability in estimation using one of these analytes as an independent variable.     

Risk factors for popliteal and carotid wall thicknesses in the Atherosclerosis Risk in Communities (ARIC) Study

The authors evaluated risk factors potentially associated with the development of popliteal artery atherosclerosis in a population-based study and compared them with factors linked to carotid wall intimal-medial thickness. The Atherosclerosis Risk in Communities (ARIC) Study is a longitudinal investigation of cardiovascular disease in 15,800 individuals. The present analyses are based on the baseline popliteal and carotid ultrasonography examination in 10,002 subjects conducted in 1987-1989. After adjustment for covariates, both carotid and popliteal intimal-medial thicknesses were strongly associated with male sex and age (p < 0.01), having a graded relation with increasing quartiles of plasma total cholesterol and low density lipoprotein cholesterol and with plasma triglycerides (women only for popliteal) (p < 0.01). An inverse correlation was noted between plasma high density lipoprotein cholesterol and carotid (p < 0.01) and popliteal (women only) (p < 0.05) intimal-medial thicknesses. Cigarette use (p < 0.01), a history of diabetes mellitus (p < 0.01), alcohol use, elevated systolic pressures (p < 0.01), and fibrinogen levels (p < 0.01) were directly associated with both popliteal and carotid intimal-medial thicknesses. Although menopause was associated with thickened carotid (p < 0.01) and popliteal (p < 0.05) intimal-medial thicknesses, hormone replacement therapy was associated with thinner carotid walls only (p < 0.05). Although there were some differences, many of the classical risk factors associated with cardiovascular disease were also related to early thickening of both the popliteal and the carotid artery walls.     

The Atherosclerosis Risk in Communities (ARIC) Study. Introduction and objectives of the hemostasis component.

The Atherosclerosis Risk in Communities (ARIC) Study is an observational epidemiologic study conducted in four communities. ARIC has two major components: One records the occurrence of myocardial infarction resulting in hospitalization and coronary heart disease death in adults aged 35 to 74 living in the communities; the other is a prospective study of representative cohorts aged 45 to 64. Measurement of hemostatic factors is part of the cohort study, whose major objectives include investigating etiologic factors associated with atherosclerosis and its clinical outcomes. Arterial intimal-medial wall thickness, an index of early atherosclerosis, is measured precisely from ultrasound images of carotid and popliteal arteries. Participants (n = 15,801) completed their first examination, which included measurements of factors associated with coagulation (fibrinogen, factor VII, factor VIII, and von Willebrand factor) and coagulation inhibition (protein C and antithrombin III). Measures of coagulation activation, platelet activation, and fibrinolytic activity will be performed on stored plasma from selected case patients and control subjects.     

Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study.

Recent epidemiologic studies found that there is a strong association of hemostatic factors with ischemic heart disease. The Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability (IIV) Study was conducted to estimate the various components of variation in hemostasis factors measured in the ARIC Study and to estimate the measures of repeatability of these factors. A total of 39 subjects (16 men, 23 women) were studied. Each had blood collected three times, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person (biologic) variability, and processing and assay variability were estimated. Then the reliability coefficient R was estimated as the proportion of total variance accounted for by between-person variance. The reliability coefficient can be interpreted as the correlation between measures made at repeat visits. Among the various analytes, the reliability coefficients were quite high for activated partial thromboplastin time and plasma factor VIII (R = 0.92, 0.86, respectively). Low repeatability was obtained for antithrombin III activity and protein C (R = 0.42, 0.56, respectively). The lack of repeatability for these variables derives mostly from the processing (field center and laboratory) variation. Other analytes--fibrinogen, plasma factor VII, and von Willebrand factor--were intermediate in repeatability. In comparing the analyte-specific high-level to low-level groups, no substantial difference of within-person plus method coefficient of variation between the two groups was found for any analyte except for factor VIII, whereas the corresponding variance components for most analytes were higher for the higher analyte level. Reliability coefficients from this ARIC IIV study are generally higher than those found in other studies, and this is related to the relative variations in populations studied and to the time between measurements.     

Neighbourhood differences in diet: the Atherosclerosis Risk in Communities (ARIC) Study

STUDY OBJECTIVE: To investigate whether neighbourhood characteristics are related to dietary patterns independently of individual level variables. DESIGN: A cross sectional analysis of the relation between neighbourhood median household income and food and nutrient intakes, before and after adjustment for individual level variables. SETTING: Four United States communities (Washington Co, MD; Suburban Minneapolis, MN; Forsyth Co, NC, and Jackson, MS). PARTICIPANTS: 13,095 adults aged 45 to 64 years participating in the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of atherosclerosis. MEASUREMENTS AND MAIN RESULTS: Information on diet and individual level income was obtained from the baseline examination of the ARIC Study. Diet was assessed using a semi-quantitative food frequency questionnaire. Information on neighbourhood (census defined block groups) median household income was obtained from the 1990 US Census. Multilevel models were used to account for the multilevel structure of the data. Living in lower income neighbourhoods was generally associated with decreased energy adjusted intake of fruits, vegetables, fish, and increased intake of meat. Patterns generally persisted after adjustment for individual level income, but were often not statistically significant. Inconsistent associations were recorded for the intake of saturated fat, polyunsaturated fat, and cholesterol. Overall, individual level income was a more consistent predictor of diet than neighbourhood income. CONCLUSION: Despite limitations in the definition and characterisation of neighbourhoods, this study found consistent (albeit small) differences across neighbourhoods in food intake, suggesting that more in depth research into potential neighbourhood level determinants of diet is warranted.     

Relations between hemostasis variables and cardiovascular risk factors in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

The relations between hemostatic variables and cardiovascular risk factors were examined in a biracial population sample of middle-aged adults. Fibrinogen, factor VII, factor VIII, von Willebrand factor, protein C, and antithrombin III levels varied considerably by age, sex, and race. Hemostatic variables also were associated with several life-style and biochemical risk factors. For the most part, higher levels of the risk factors were associated with higher levels of the hemostatic variables. The findings point to potential confounders that warrant consideration in cardiovascular disease studies, and/or mechanisms by which cardiovascular risk is conferred. They also suggest that modification of the cardiovascular risk factors may have the potential to alter the risk of thrombosis.     

Leukocyte count correlates in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study.

Cross-sectional associations between leukocyte count and sociodemographic and cardiovascular risk factors were investigated in 14,679 participants aged 45-64 years in the Atherosclerosis Risk in Communities Study carried out in four US communities in 1986-1989. Leukocyte count was strongly associated with present or past history of cigarette smoking and was higher in males than in females and in white subjects than in black subjects. Among never smokers, no sex differences were evident after adjustment for other risk factors. Race-associated differences were substantially reduced after other factors were taken into account in multivariate analyses. In never smokers, leukocyte count was higher in those who reported poor health, and it was inversely associated with high density lipoprotein cholesterol, forced expiratory volume at 1 second, physical activity, and, among whites, height and socioeconomic indicators. It was directly associated with indices of body weight and body fat, heart rate, blood pressure, hemoglobin, platelet count, uric acid, fasting insulin and glycemia, triglycerides, fibrinogen, antithrombin III, protein C, factors VII and VIII, and von Willebrand factor. The associations of leukocyte count with cardiovascular risk factors may either represent manifestation of subclinical disease or suggest that leukocyte count is part of the causal chain leading to atherosclerosis. Alternatively, the relation of leukocyte count to cardiovascular disease may be confounded by risk factors and thus be noncausal.     

Association of coagulation factors and inhibitors with carotid artery atherosclerosis. Early results of the Atherosclerosis Risk in Communities (ARIC) Study.

Several population studies have shown that plasma levels of fibrinogen and factor VII are significantly associated with ischemic cardiovascular events. However, there is little information regarding the association of hemostatic factors with early atherosclerosis. To evaluate this, we compared the plasma concentrations of several coagulation proteins (fibrinogen, factor VII, factor VIII, von Willebrand factor, protein C, and antithrombin III) between 385 case patients, defined by high-resolution B-mode ultrasonography as having carotid arterial wall thickening, and 385 age-, race-, and sex-matched control subjects. These case patients and control subjects were selected from participants in a prospective population investigation, the Atherosclerosis Risk in Communities (ARIC) Study, who were examined between May 1987 and May 1989. Plasma fibrinogen, factor VII, protein C, and antithrombin III levels were significantly higher in case patients than in control subjects (P < 0.05). Factor VIII and von Willebrand factor were not different. These findings were supported by quartile distribution and univariate analysis. However, only fibrinogen remained significantly associated with carotid atherosclerosis on multivariate analysis taking other atherosclerosis risk factors into consideration. A one standard deviation increase in fibrinogen (67 mg/dL) was associated with a 1.6-fold increase in the odds of carotid atherosclerosis univariately (P < 0.001) and with a 1.3-fold increase in the odds multivariately (P = 0.010). Further analysis revealed that the association of fibrinogen with carotid atherosclerosis was somewhat stronger in cigarette smokers than in nonsmokers. This early case-control analysis of the ARIC Study demonstrates a significant association between plasma fibrinogen concentration and early atherosclerosis in the carotid arteries. In the context of published findings from population studies, our results indicate that plasma fibrinogen concentrations may be a useful marker for identifying individuals at high risk of developing arterial thrombotic disorders.     

Relationship of serum and dietary magnesium to incident hypertension: the Atherosclerosis Risk in Communities (ARIC) Study

PURPOSE: To examine the relationship of serum and dietary magnesium (Mg) with incident hypertension. The setting was the Atherosclerosis Risk in Communities (ARIC) Study, which included a biracial cohort, aged 45-64 years, from four U.S. communities. METHODS: This analysis included 7731 participants (4190 women and 3541 men) free of hypertension at baseline and followed six years. Fasting serum Mg was measured, and usual dietary intake was assessed with a food frequency questionnaire. RESULTS: After adjustment for age, race, and a number of other risk factors, the odds of incident hypertension across ascending quartiles of serum Mg were 1.0, 0.79, 0.85, and 0.70 in women (p trend = 0.01) and 1.0, 0.87, 0.87, and 0.82 in men (p trend = 0.16). We found no association between dietary Mg intake and incident hypertension. These associations were attenuated after the addition of baseline systolic blood pressure to the models. CONCLUSIONS: This study suggests that low Mg may play a modest role in the development of hypertension.     

Cholesterol, high density lipoprotein cholesterol and triglycerides during puberty: the Oslo Youth Study

The relationships of serum total cholesterol, high density lipoprotein (HDL) cholesterol and fasting triglycerides (adjusted for body mass index, wt/ht2) with stages of pubertal development were examined in a Norwegian population of 920 adolescents, aged 10 to 16 years. For 13- and 14-year-olds, all five stages of Tanner's maturity index were represented. For the whole population, total serum cholesterol showed a larger decrease when related to sexual maturity stage than to chronologic age. For females, HDL cholesterol and triglycerides increased significantly when related to age in years; this was not found when related to the maturity index. Triglycerides showed a larger increase when related to chronologic age in males as compared with sexual maturity stage. Both among 13- and 14-year-old males, the most mature had significantly lower values for total cholesterol than the least mature. For 12-year-old males, HDL cholesterol decreased significantly with increasing sexual maturation. Among females, the more mature 12-year-olds had significantly lower values for total cholesterol compared with the less mature. Early maturing 13-, 14- and 15-16-year-olds had lower levels of HDL cholesterol compared with late maturers. These findings suggest that age in years may be a poor index of development in adolescents and that a measure of physiologic developmental age should be included in epidemiologic studies of serum lipids among adolescents.     

Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) Study

PURPOSE: Approximately half of previous studies on serum uric acid have reported it to be an independent risk factor for coronary heart disease (CHD). We tested this hypothesis in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: A total of 13,504 healthy middle-aged men and women were followed prospectively for up to eight years. We identified 128 fatal and nonfatal CHD events in women and 264 in men. RESULTS: The age-, race-, and ARIC field center-adjusted relative risk of CHD for sex-specific quartiles of serum uric acid were 1.0, 1.39, 1.08, and 2.35 in women (p for trend = 0.009) and 1.0, 1.03, 0.89, and 1.21 in men (p for trend = 0.44), respectively. However, serum uric acid was correlated positively with many risk factors, and after multivariable adjustment, there was little evidence of an association of uric acid with CHD in either sex. CONCLUSIONS: Our results are not consistent with serum uric acid being an independent risk factor for CHD.     

甘油三酯、高密度脂蛋白变化与空腹血糖变化的 5年随访研究

摘要:目的　探讨甘油三酯（TG）、高密度脂蛋白（HDL）、甘油三酯/高密度脂蛋白（TG/ HDL）变化对2 型糖尿病发病的影响。方法　基线人群为石家庄市6个企事业单位职工,排除标准为糖尿病、冠心病、恶性肿瘤、肾衰及空腹血糖（FPG）≥5.6 mmol/L,进行连续5年随访,比较TG、HDL、TG/ HDL不同变化下FPG变化率,运用Logistic 回归模型分析研究三者变化与FPG变化的关系。结果　在随访过程中TG、HDL、TG/ HDL未控制组FPG变化高于三者保持正常或控制组,差异有统计学意义（P＜0.05）。Logistic 回归分析与各组在基线正常随访过程中仍保持正常相比,FPG变化TG组边缘升高转为TG升高RR值2.642（95% CI 1.572～4.379）、保持TG升高组RR值2.136（95% CI 1.455～3.135）、TG正常转为TG升高RR值1.969（95% CI 1.572～4.379）、TG升高转为TG边缘升高RR值1.954（95% CI 1.084～3.522）、保持TG边缘升高RR值1.717（95% CI 1.110～2.654）、TG正常转为TG边缘升高RR值1.64（95% CI 1.183～2.273）、TG边缘升高转为TG正常RR值1.495（95% CI 1.032～2.167）;HDL组RR值最高为HDL正常转为HDL减低1.857（95% CI 1.620～2.129）;TG/HDL组RR值由高至低为比值仍保持升高组（RR值7.506,95% CI 1.431～4.388）、比值正常转为升高组（RR值2.453,95% CI 1.365～4.408）。结论　TG、HDL 及 TG/HDL比值长期的变化与空腹血糖水平明显相关,血脂代谢异常在2型糖尿病的发生发展中可能扮演着重要角色。     

Workplace exposure to environmental tobacco smoke and high density lipoprotein cholesterol among nonsmokers

There are few epidemiologic studies among adult nonsmokers on the effects of workplace environmental tobacco smoke on high density lipoprotein cholesterol (HDL-C). The authors investigated this relation, using data from health examinations conducted in 1995 on 3,062 Japanese nonsmokers in a total of 27 municipal offices with few smoking restrictions. Multiple regression analysis with adjustments for age, body mass index, alcohol drinking, and sports activities showed that in women, and in men lacking both alcohol consumption and sports activities characteristics, there were inverse linear relations between workplace smoking indices and HDL-C levels. Multivariate logistic regression showed that nonsmoking women in the upper two thirds of offices ranked by smoking intensity had an increased risk of low HDL-C levels (<45 mg), taking those in the lowest third of offices as reference (the medium third: odds ratio = 1.7; 95% confidence interval: 1.2, 2.5; the highest third: odds ratio = 1.6; 95% confidence interval: 1.1, 2.4). The results indicated that workplace environmental tobacco smoke exposure is associated with HDL-C among nonsmokers. However, the lack of data on home exposure limits causal inferences about the effects of workplace exposure.     

Validation of death certificate diagnosis for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study

The validity of the death certificate in identifying coronary heart disease deaths was evaluated using data from the community surveillance component of the Atherosclerosis Risk in Communities Study (ARIC). Deaths in the four ARIC communities of Forsyth Co., NC; Jackson, MS; Minneapolis, MN; and Washington Co., MD were selected based on underlying cause of death codes as determined by the rules of the ninth revision of the International Classification of Diseases (ICD-9). Information about the deaths was gathered through informant interviews, physician or coroner questionnaires, and medical record abstraction, and was used to validate the cause of death. Sensitivity, specificity, and positive predictive value of the death certificate classification of CHD death (ICD-9 codes 410-414 and 429.2) were estimated by comparison with the validated cause of death based on physician review of all available information. Results from 9 years of surveillance included a positive predictive value 0.67 (95% CI 0.66-0.68), sensitivity of 0.81 (95% CI 0.79-0.83), and a false-positive rate (1-specificity) of 0.28 (95% CI 0.26-0.30). Comparing CHD deaths as defined by the death certificate with validated CHD deaths indicated that the death certificate overestimated CHD mortality by approximately 20% in the ARIC communities. Within subgroups, death certificate overestimation was reduced with advancing age (up to age 74), was consistent over time, was not dependent on gender, and exhibited considerable variation among communities.     

Occupation recorded on certificates of death compared with self-report: the Atherosclerosis Risk in Communities (ARIC) Study

Background  

Death certificates are a potential source of sociodemographic data for decedents in epidemiologic research. However, because this information is provided by the next-of-kin or other proxies, there are concerns about validity. Our objective was to assess the agreement of job titles and occupational categories derived from death certificates with that self-reported in mid and later life.     

Genetic Markers Associated With Plasma Protein C Level in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

Protein C is an endogenous anticoagulant protein with anti‐inflammatory properties. Single‐nucleotide polymorphisms (SNPs) affect the levels of circulating protein C in European Americans. We performed a genome‐wide association (GWA) scan of plasma protein C concentration with approximately 2.5 million SNPs in 2,701 African Americans in the Atherosclerosis Risk in Communities Study. Seventy‐nine SNPs from the 20q11 and 2q14 regions reached the genome‐wide significance threshold of 5 × 10^‐8. A missense variant rs867186 in the PROCR gene at 20q11 is known to affect protein C levels in individuals of European descent and showed the strongest signal (P = 9.84 × 10^‐65) in African Americans. The minor allele of this SNP was associated with higher protein C levels (β = 0.49 μg/ml; 10% variance explained). In the 2q14 region, the top SNPs were near or within the PROC gene: rs7580658 (β = 0.15 μg/ml; 2% variance explained, P = 1.7 × 10^‐12) and rs1799808 (β = 0.15 μg/ml; 2% variance explained, P = 2.03 × 10^‐12). These two SNPs were in strong linkage disequilibrium (LD) with another SNP rs1158867 that resides in a biochemically functional site and in weak to strong LD with the top PROC variants previously reported in individuals of European descent. In addition, two variants outside the PROC region were significantly and independently associated with protein C levels: rs4321325 in CYP27C1 and rs13419716 in MYO7B. In summary, this first GWA study for plasma protein C levels in African Americans confirms the associations of SNPs in the PROC and PROCR regions with circulating levels of protein C across ethnic populations and identifies new candidates for protein C regulation.     

A prospective study of plasma ferritin level and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study

The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development.