Modelling the association between patient characteristics and the change over time in a disease measure using observational cohort data

In observational cohort studies we may wish to examine the associations between fixed patient characteristics and the longitudinal changes from baseline in a repeated outcome measure. Many biological and other outcome measures are known to be subject to measurement error and biological variation. In an initial analysis we may fit a regression model to all outcome measurements, accounting for all the identified sources of variability, and see how the characteristics are linked to the change for typical patients. However, the characteristics may also be linked to different distributions of the underlying outcome value at baseline, which itself may be correlated with the change over time. Therefore, if we wish to examine the change over time for patients of different characteristics but with the same underlying baseline value then the initial approach is confounded by the baseline values. Furthermore, if we attempt to remove this confounding by including the observed baseline measure as a covariate in a model for later measurements, then this may provide an approximate solution but is likely to introduce some bias. We propose a method based on first following the initial approach but then, applying a correction to the parameter estimates. This allows the predicted trajectories to be plotted and valid significance tests of association with characteristics. Our approach is compared with other methods and illustrated through a simulation study and an analysis of the association between HIV‐1 subtype and immunological response after starting antiretroviral therapy. Copyright © 2009 John Wiley & Sons, Ltd.     

The use of repeated blood pressure measures for cardiovascular risk prediction: a comparison of statistical models in the ARIC study

Many prediction models have been developed for the risk assessment and the prevention of cardiovascular disease in primary care. Recent efforts have focused on improving the accuracy of these prediction models by adding novel biomarkers to a common set of baseline risk predictors. Few have considered incorporating repeated measures of the common risk predictors. Through application to the Atherosclerosis Risk in Communities study and simulations, we compare models that use simple summary measures of the repeat information on systolic blood pressure, such as (i) baseline only; (ii) last observation carried forward; and (iii) cumulative mean, against more complex methods that model the repeat information using (iv) ordinary regression calibration; (v) risk‐set regression calibration; and (vi) joint longitudinal and survival models. In comparison with the baseline‐only model, we observed modest improvements in discrimination and calibration using the cumulative mean of systolic blood pressure, but little further improvement from any of the complex methods. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.     

The association between homocysteine levels,Mediterranean diet and cardiovascular disease: a case-control study

The aim was to investigate the association between homocysteine (Hcy) and acute coronary syndrome (ACS) and to test the potential moderating role of Mediterranean diet. An age and gender matched case-control study was conducted among 1491 patients with a first ACS event and 3037 adults free of cardiovascular disease (CVD). Adherence to the Mediterranean diet was measured using the MedDietScore (range 0–55). An increase in Hcy levels was associated with a 1% and 3% higher likelihood of ACS among younger (<45 yrs) and middle-aged (45–60yrs) adults (p’s?<?0.05), but not in older adults (p?=?0.13). Moreover, Hcy was associated with 3% (95%CI: 1.01–1.06) increase in the likelihood of ACS among those who did not adhere to the Mediterranean diet. Hence, Hcy is apparently independently associated with ACS among younger and middle-aged individuals. The inverse association between Mediterranean diet adherence and Hcy highlights a disease-preventing effect of the Mediterranean diet on CVD.     

Multi‐state Markov models for disease progression in the presence of informative examination times: An application to hepatitis C

In many chronic diseases it is important to understand the rate at which patients progress from infection through a series of defined disease states to a clinical outcome, e.g. cirrhosis in hepatitis C virus (HCV)‐infected individuals or AIDS in HIV‐infected individuals. Typically data are obtained from longitudinal studies, which often are observational in nature, and where disease state is observed only at selected examinations throughout follow‐up. Transition times between disease states are therefore interval censored. Multi‐state Markov models are commonly used to analyze such data, but rely on the assumption that the examination times are non‐informative, and hence the examination process is ignorable in a likelihood‐based analysis. In this paper we develop a Markov model that relaxes this assumption through the premise that the examination process is ignorable only after conditioning on a more regularly observed auxiliary variable. This situation arises in a study of HCV disease progression, where liver biopsies (the examinations) are sparse, irregular, and potentially informative with respect to the transition times. We use additional information on liver function tests (LFTs), commonly collected throughout follow‐up, to inform current disease state and to assume an ignorable examination process. The model developed has a similar structure to a hidden Markov model and accommodates both the series of LFT measurements and the partially latent series of disease states. We show through simulation how this model compares with the commonly used ignorable Markov model, and a Markov model that assumes the examination process is non‐ignorable. Copyright © 2010 John Wiley & Sons, Ltd.     

The relation between alcohol and cardiovascular disease in Eastern Europe: explaining the paradox

BACKGROUND: Recent evidence from Eastern Europe of a positive association between alcohol and cardiovascular disease has challenged the prevailing view that drinking is cardioprotective. Consuming amounts of alcohol comparable to those consumed in France has been linked to detrimental cardiovascular effects. One possibility is that this could be related to the particular consequences of binge drinking, which is common in Russia. METHODS: A systematic review of literature on the relation between cardiovascular disease and heavy drinking and irregular (binge) drinking. RESULTS: Most existing reviews of the relation between alcohol and cardiovascular disease have examined the amount drunk per week or month and have not looked at the pattern of drinking. These have consistently shown that alcohol has a cardioprotective effect, even at high levels of consumption. In contrast, studies that have looked at pattern of drinking, either directly, or indirectly, using indicators such as frequency of hangovers or reports of the consequences of drunkenness, have consistently found an increased risk of cardiovascular death, particularly sudden death. A separate review of the physiological basis for a difference between regular heavy drinking and heavy binge drinking demonstrates that the two types of drinking have quite different effects. CONCLUSION: An association between binge drinking and cardiovascular death meets the standard criteria for causality. It is important that future studies of alcohol related harm examine the pattern of drinking as well as the amount drunk.     

A comparison of the association between socioeconomic position and cardiovascular disease risk factors in three age cohorts of Australian women: findings from the Australian Longitudinal Study on Women's Health

OBJECTIVES: To assess the associations between three measurements of socioeconomic position (SEP) -- education, occupation and ability to cope on available income -- and cardiovascular risk factors in three age cohorts of Australian women. METHODS: Cross-sectional analysis of three cohorts of Australian women aged 18-23, 45-50 and 70-75 years. RESULTS: In general, for all exposures and in all three cohorts, the odds of each adverse risk factor (smoking, obesity and physical inactivity) were lower in the most advantaged compared with the least advantaged. Within each of the three cohorts, the effects of each measurement of SEP on the outcomes were similar. There were, however, some notable between-cohort differences. The most marked differences were those with smoking. For women aged 70-75 (older), those with the highest educational attainment were more likely to have ever smoked than those with the lowest level of attainment. However, for the other two cohorts, this association was reversed, with a stronger association between low levels of education and ever smoking among those aged 18-23 (younger) than those aged 45-50 (mid-age). Similarly, for older women, those in the most skilled occupational classes were most likely to have ever smoked, with opposite findings for mid-age women. Education was also differently associated with physical inactivity across the three cohorts. Older women who were most educated were least likely to be physically inactive, whereas among the younger and mid-age cohorts there was little or no effect of education on physical inactivity. CONCLUSION: These findings demonstrate the dynamic nature of the association between SEP and some health outcomes. Our findings do not appear to confirm previous suggestions that prestige-based measurements of SEP are more strongly associated with health-related behaviours than measurements that reflect material and psychosocial resources.     

A systematic review of analytical observational studies investigating the association between cardiovascular disease and drinking water hardness

The aim of this study is to systematically review and critically assess analytical observational epidemiology studies investigating the association between levels of drinking water hardness and cardiovascular disease. We searched electronic databases and used standardised forms to extract data and assess study quality. Of 2,906 papers identified, 14 met the inclusion criteria (nine case control and five cohort studies). Of the nine case control studies, seven examined both drinking water magnesium and calcium and risk of death from cardiovascular disease. A pooled odds ratio showed a statistically significant inverse association between magnesium and cardiovascular mortality (OR 0.75 (95%CI 0.68, 0.82), p < 0.001). Only two studies reported a statistically significant effect for calcium. Substantial heterogeneity between studies made calculation of a summary estimate for drinking water calcium inappropriate. Of three cohort studies reviewed, two were of good quality. A weak suggestion that soft water was harmful in females and possibly associated with a slightly greater risk of sudden death was reported, but there was no association between water hardness and mortality from stroke or cardiovascular disease. This study found significant evidence of an inverse association between magnesium levels in drinking water and cardiovascular mortality following a meta-analysis of case control studies. Evidence for calcium remains unclear.     

最新血压标准变化下高血压与心血管疾病关联

目的 本文探究了2020 ISH高血压指南与2017 ACC/AHA高血压指南定义下的血压标准与天津市老年人特别是原定义为高值血压现定义为正常血压人群的心血管疾病发生风险的关联,为进一步评价2020 ISH新指南定义标准在预防心血管疾病的应用中提供参考。方法 基于2014年进入天津市居民健康档案队列,通过整群抽样,选取天津市部分地区60岁以上191 043名老年人的血压测量随访数据。血压诊断采用2种标准:2017 ACC/AHA高血压指南、2020 ISH高血压指南。统计学方法采用卡方检验、独立样本t检验及Cox比例风险模型。结果 介于120/80 mm Hg与130/85 mm Hg之间的血压值在2017年ACC/AHA指南中为高值血压,但在2020年ISH新的血压指南中为正常血压。此区间的51 605名老年人群发生主要心血管事件的风险HR=1.248,95%CI: 1.187～1.313,高于两个标准下均为正常血压的人群,HR有统计学意义。结论 位于120/80～130/85 mm Hg区间的107 575名人群可能会增加CVD发生风险,仍需密切关注。应基于我国实际人口发展状况,采取高血压防线关口前移策略,通过控制发病率降低实现更加有效的防治。     

Repeated-measures model for the investigation of temporal trends using longitudinal family studies: application to systolic blood pressure

A contemporary path model for the analysis of familial resemblance is extended to incorporate repeated measurements on the entire pedigree over time, in order to assess age-related changes in familiality. The parameters of the model can be defined as arbitrary functions of the ages, age differences, or cohabitation times of the family members at the exact time of measurement. Tracking of the phenotypes is decomposed into a familial and a nonfamilial component, which varies with both the time span between measurements and the ages at measurement. Some of the family members may have data missing on one or more visits, and the visits may be unequally spaced both within and across families. The method incorporates all measurements available from all visits into a single model. The model is applied to longitudinal data on systolic blood pressure in 490 East Boston families measured two times at 3-year intervals. Evidence for some nonfamilial tracking is found. Additionally, significant temporal trends are demonstrated in the familiality as a function of age, t2(A), which appears to be near zero at birth, grow to a maximum of about 40% at around age 30, and then appears to monotonically decrease again. No evidence was found for temporal trends in marital resemblance or residual sibling environmental effects. This model provides an objective method of investigating developmental changes in the correlational structure of families over time using repeated-measures and of estimating continuous changes in familiality with age.     

Separating within and between effects in family studies: an application to the study of blood pressure in children

In epidemiology the analyses of family or twin studies do not always fully exploit the data, as information on differences between siblings is often used while between-families effect are not considered. We show how cross-sectional time-series linear regression analysis can be easily implemented to estimate within- and between-families effects simultaneously and how these effects can then be compared using the Hausman test. We illustrate this approach with data from the Uppsala family study on blood pressure in children with age ranging from 5.5 to 12.3 years for the younger and from 7.5 to 13.8 years for the older siblings. Comparing the effect of differences in birth weight on blood pressure within-family (in full siblings) and between-families (in unrelated children) allows us to study the contributions of fixed and pregnancy-specific maternal effects on birth weight and consequently on blood pressure. Our data showed a 0.88 mmHg decrease (95 per cent confidence interval: -1.7 to -0.03 mmHg) in systolic blood pressure for one standard deviation increase in birth weight between siblings within a family and 0.88 mmHg (95 per cent confidence interval: -1.6 to -0.2 mmHg) decrease in systolic blood pressure for one standard deviation increase in birth weight between unrelated children. These estimates were controlled for sex, age, pubertal stage, body size and pulse rate of the children at examination and for maternal body size and systolic blood pressure. The within- and between-families effects were not significantly different, p = 0.19, suggesting that fixed and pregnancy-specific factors have similar effects on childhood systolic blood pressure.     

Longitudinal study of the association between ABO phenotype and total serum cholesterol level in a Japanese cohort.

The relationship between ABO blood phenotype and total serum cholesterol (TC) level was examined in a Japanese population to determine whether an elevated TC level is associated with phenotype A, as has been demonstrated in many West European populations. Such studies in nonwhite populations are scarce, and findings generally failed to demonstrate the relationship. Inconsistent results from cross-sectional studies of various racial groups with widely varying ages raised an age effect as a possible explanatory factor. It was also suggested that the ABO-TC association may not be apparent in populations with low fat intake or low mean cholesterol level. These hypotheses are addressed by examining long-term TC data collected serially from the unexposed controls of the atomic bomb survivors in Hiroshima and Nagasaki who were participants of the Adult Health Study program at the Atomic Bomb Casualty Commission-Radiation Effects Research Foundation between 1958 and 1986. The statistical method of growth curve analysis, through the mixed effect model of Laird and Ware [1982], was used to model age-dependent changes in cholesterol levels within individuals. The effects of the ABO polymorphism in modifying the resultant growth curve are examined. We demonstrate that TC levels are elevated on average by about 4 mg/dl in phenotype A compared to non-A in the Japanese (P < 0.00001), and that this relationship is maintained from early to late adulthood, independent of sex, body mass index, cohort status, or city of residence. Thus, phenotype A individuals may be more predisposed to cardiovascular disease through one of its major risk factors. This is the first study of the ABO-cholesterol association in the Japanese, and the first based on a cohort with longitudinally collected TC data.     

Healthy-eating attitudes and the incidence of cardiovascular disease: the SUN cohort

There is an emerging use of brief dietary questionnaires to investigate diet-health relation. We prospectively assess the association between eating attitudes (yes/no) and incident cardiovascular disease (CVD) in 19,138 participants of the Seguimiento Universidad de Navarra (SUN) Cohort. We calculated a baseline healthy-eating attitudes score (in quartiles), positively weighting answers on more fruit, vegetables, fish and fiber and less meat, sweets and pastries, fat, butter, fatty meats and added sugar in drinks. We observed 139 incident cases of CVD. A higher score was associated with a lower risk of CVD [3-5 points Hazard Ratio (HR): 0.38 (95% confidence interval: 0.18-0.81); 6-8 points: 0.57 (0.29-1.12); 9-10 points: 0.31 (0.15-0.67), compared to 0-2 points]. Key contributors were the attitude to increase fruit [HR: 0.59 (0.40-0.87)], vegetables [HR: 0.57 (0.29-1.12)] and fiber intake [HR: 0.69 (0.48-0.98)]. Brief questionnaire on attitudes towards healthy-eating may be a useful tool for the primary prevention of CVD.     

Joint modelling of bivariate longitudinal data with informative dropout and left-censoring, with application to the evolution of CD4+ cell count and HIV RNA viral load in response to treatment of HIV infection

Several methodological issues occur in the context of the longitudinal study of HIV markers evolution. Three of them are of particular importance: (i) correlation between CD4+ T lymphocytes (CD4+) and plasma HIV RNA; (ii) left-censoring of HIV RNA due to a lower quantification limit; (iii) and potential informative dropout. We propose a likelihood inference for a parametric joint model including a bivariate linear mixed model for the two markers and a lognormal survival model for the time to drop out. We apply the model to data from patients starting antiretroviral treatment in the CASCADE collaboration where all of the three issues needed to be addressed.     

Examining the Association between Utilization Management and Downstream Cardiovascular Imaging

Objectives

To examine the association of echocardiography utilization management (EUM) program with downstream cardiac imaging utilization.

Data Sources/Study Setting

Administrative claims data from commercial health plans in Indiana, Ohio, Kentucky, Wisconsin, and Georgia.

Study Design

Patients undergoing index cardiovascular imaging with no imaging in the preceding year were identified (N = 112,308). Claims-derived cardiac risk scores were used for one-to-one propensity score matching of patients subject to EUM to patients without EUM (n = 96,906). Downstream cardiac imaging utilization for 12–24 months postindex imaging was analyzed using generalized linear models and Cox proportional hazards model.

Principal Findings

Downstream cardiac imaging tests were performed for 10,630 (21.9 percent) and 12,012 (24.8 percent) patients in the EUM and non-EUM groups, respectively. At 12-month follow-up, adjusted utilization was 15.2 (95 percent CI, 7.6–22.5) tests per 1,000 initially tested patients lower in the EUM group (p < .001). The likelihood of obtaining downstream cardiac imaging in the EUM group was 7.0 percent lower than the non-EUM group (hazard ratio: 0.930; 95 percent CI, 0.897–0.964, p < .001).

Conclusions

Downstream cardiac imaging is relatively common among commercially insured patients. Every 10 initial diagnostic tests yielded two downstream imaging tests in first 24 months. EUM program was associated with lower volumes of downstream imaging.     

Effectiveness calculation in economic analysis: the case of statins for cardiovascular disease prevention

OBJECTIVES: This report aimed to evaluate the calculation of estimates of effectiveness in cost effectiveness analyses of statins for cardiovascular disease prevention. METHODS: Methodological aspects were reviewed of seven primary studies (based on trial results) and 12 secondary modelling studies (extrapolated) on the cost effectiveness of statin treatment, published between 1995 and 2002. Estimates of life years gained were extracted and compared with estimates calculated using the Dutch male life table of 1996-2000. RESULTS: Of the seven primary modelling analyses, six showed all the essential data. They estimated that 3 to 5.6 years (average 4.6 years) of statin treatment resulted in 0.15 to 0.41 years (average 0.3 years) saved over a lifetime time horizon. In contrast none of the 12 secondary modelling studies provided transparent results. They assumed lifelong treatment, leading to life table estimations of 2.4 and 2.0 (undiscounted) years saved for 40 and 60 year olds, with peak savings at around the mean age of death: 75-80 years. With 5% discounting, these effects reduced to 0.4 and 0.8 years respectively. CONCLUSION: Reporting of essential data and assumptions on statin treatment was poor for secondary modelling analyses and satisfactory for primary modelling studies. Secondary modeling studies made assumptions on long term effectiveness that were hard to justify with the available evidence, and that led to the majority of life years saved at high ages. Further standardisation in economic analyses is important to guarantee transparency and reproducibility of results.     

理想心血管健康行为和因素与非酒精性脂肪肝的相关性研究

目的 探讨理想心血管健康行为和因素与非酒精性脂肪肝(NAFLD)的关系.方法 以参加2006-2007年度健康体检的101 510名开滦集团公司职工为研究对象,排除饮酒者、心肌梗死、脑卒中、恶性肿瘤以及资料不全者,最终纳入54 303例,观察研究人群中NAFLD的患病情况.根据美国心脏协会定义的理想心血管健康行为和因素,采用多因素logistic回归模型分析理想心血管健康行为和因素与NAFLD的关系.结果 具备0～1、2、3、4、5～7个理想心血管健康行为和因素组的NAFLD患病率分别为62.6％、48.9％、33.3％、16.1％和7.5％ (P＜0.000 1).校正年龄、性别、经济收入水平、文化程度等混杂因素后,理想心血管健康行为和因素与NAFLD有关,且随着健康行为和因素个数的增多(0～1、2、3、4、5～7),OR值(95％CI)逐渐降低,分别为1、0.61(0.56～0.66)、0.37(0.34～0.40)、0.17(0.15 ～0.18)和0.08(0.07 ～0.09).结论 理想心血管健康行为和因素与NAFLD相关.     

The effect of dental care on cardiovascular disease outcomes: an application of instrumental variables in the presence of heterogeneity and self-selection

Studies show a relationship between oral inflammatory processes and cardiovascular risk factors, suggesting that dental care may reduce the risk of cardiovascular disease (CVD) events. However, due to the differences between men and women in the development and presentation of CVD, such effects may vary by sex. We use a valid set of instrumental variables to evaluate these issues and include a test of essential heterogeneity. CVD events include new occurrences of heart attack (including death from heart attack), stroke (including death from stroke), angina, and congestive heart failure. Controls include age, race, education, marital status, foreign birthplace, and cardiovascular risk factors (health status, body mass index, alcohol use, smoking status, diabetes status, high-blood-pressure status, physical activity, and depression). Our analysis finds no evidence of essential heterogeneity. We find the minimum average treatment effect for women to be -0.01, but find no treatment effect for men. This suggests that women who receive dental care may reduce their risk of future CVD events by at least one-third. The findings may only apply to married middle-aged and older individuals as the data set is only representative for this group.     

Associations between recent exposure to ambient fine particulate matter and blood pressure in the Multi-ethnic Study of Atherosclerosis (MESA)

BACKGROUND: Blood pressure (BP) may be implicated in associations observed between ambient particulate matter and cardiovascular morbidity and mortality. This study examined cross-sectional associations between short-term ambient fine particles (particulate matter 相似文献   

Determinants of patient activation and its association with cardiovascular disease risk in chronic kidney disease: A cross‐sectional study

BackgroundPatient activation describes the knowledge, skills and confidence in managing one''s own health. Promoting patient activation is being prioritized to reduce costs and adverse outcomes such as cardiovascular disease (CVD). The increasing prevalence of chronic kidney disease (CKD) presents a need to understand the characteristics that influence patient activation and the effect on health outcomes.DesignCross‐sectional study.Setting and participantsPatients with non‐dialysis CKD recruited from 14 sites (general nephrology and primary care) in England, UK.Outcome measuresPatient activation was measured using the PAM‐13. Demographic and health‐related variables, self‐reported symptom burden, health‐related quality of life (HRQOL), socioeconomic status (SES), were assessed as determinants of patient activation. Major CVD risk factors included hypertension, dyslipidaemia, obesity and hyperkalaemia.Results743 patients were included (eGFR: 32.3 (_SD17.1) mL/min/1.73 m², age 67.8 (_SD13.9) years, 68% male). The mean PAM score was 55.1 (_SD14.4)/100. Most patients (60%) had low activation. Those with low activation were older (P<.001), had lower eGFR (P = .004), greater number of comorbidities (P = .026) and lower haemoglobin (P = .025). Patients with low activation had a 17% greater number of CVD risk factors (P < .001). Risk factors in those with low activation were being older (P < .001) and having diabetes (P < .001).ConclusionThis study showed that only a minority of CKD patients are activated for self‐management. Our findings help better understand the level of activation in these patients, particularly older individuals with multimorbidity, and further the knowledge regarding the characteristics that influence activation.Patient or Public ContributionPatients were involved in the design of main study.