No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
A new estimate of family disease history providing improved prediction of disease risks
Abstract
Complex diseases often aggregate within families and using the history of family members' disease can potentially increase the accuracy of the risk assessment and allow clinicians to better target on high risk individuals. However, available family risk scores do not reflect the age of disease onset, gender and family structures simultaneously. In this paper, we propose an alternative approach for a family risk score, the stratified log-rank family score (SLFS), which incorporates the age of disease onset of family members, gender differences and the relationship among family members. Via simulation, we demonstrate that the new SLFS is more closely associated with the true family risk for the disease and more robust to family sizes than two existing methods. We apply our proposed method and the two existing methods to a study of stroke and heart disease. The results show that assessing family history can improve the prediction of disease risks and the SLFS has strongest positive associations with both myocardial infarction and stroke.
... This study, however, was based on self-administered questionnaires dichotomizing familial history instead of using gold standard pedigree interviews. Besides the risk of misclassification it does not capture the number of affected family members and age upon CAD onset, which may influence heritability and hence reduce the ability to predict future disease among relatives [16,20,21]. Therefore, we aimed to quantify the polygenic burden (measured as a 45-SNP GRS) in early-onset CAD patients and to investigate whether early-onset individuals with a strong familial clustering of CAD had a larger proportion of common risk alleles. ...
... For all patients with early-onset CAD, the family pedigrees were used to calculate a stratified log-rank family risk score (SLFS), which is a single measure of family history severity. The SLFS was chosen for the present study since it simultaneously considers the age at time of CAD onset in relatives, taking into account the relationship and differences in CAD risk among men and women [21]. The calculation and validation of the SLFS has previously been described [21]. ...
... The SLFS was chosen for the present study since it simultaneously considers the age at time of CAD onset in relatives, taking into account the relationship and differences in CAD risk among men and women [21]. The calculation and validation of the SLFS has previously been described [21]. Briefly, for a given family member type (in the following we consider fathers) the age of CAD onset (i.e. ...
Background and aims:
Common genetic risk variants may contribute to the heritability of early-onset coronary artery disease (CAD). We aimed to investigate the association of a genetic risk score (GRS) with age upon CAD-onset and to test the association between the GRS, familial clustering, and CAD severity in early-onset CAD.
Methods:
134 early-onset CAD patients (<40 years), 446 late-onset CAD patients (male >55 years/female >65 years), and 89 healthy controls were genotyped for 45 CAD-associated SNPs and a GRS was created. In early-onset CAD patients, family pedigrees with information on 1585 1st and 2nd degree relatives were used to calculate a stratified log-rank family score (SLFS) as a measure of familial clustering.
Results:
Early-onset patients had a higher mean GRS than late-onset CAD patients (p = 0.02) and healthy controls (p < 0.0001). In the adjusted model, a GRS increase of one SD was associated with 1.2 years (95% CI 0.1-2.2) earlier onset. The GRS was not associated with the SLFS in the regression model (p = 0.41) and did not differ between SLFS tertiles (p = 0.98). The SLFS predicted the number of affected coronary vessels (OR [95% CI] per SD increase in SLFS: 2.0 [1.4-3.0]), whereas the association between the GRS and CAD severity was not statistically significant (OR [95% CI] per SD increase in GRS: 1.3 [0.9-1.9]).
Conclusions:
The GRS was increased in early-onset CAD patients, but not associated with the SLFS, suggesting that these common genetic variants are of minor importance in familial clustering of early-onset CAD. Furthermore, family pedigree analysis may predict CAD severity more precisely than common variants.
... Within each time interval, the subcomponent of the long-rank statistic, as the difference between the observed and expected numbers of failures, can serve as a standardized measure of observed extremeness and has been used to compare two groups [6]. In a previous study [7], we have proposed a stratified log-rank score (LRS) to quantify family disease history, which accounts for the age of disease onset and disease status jointly. In this study, we would focus on separate parental influences. ...
... Other factors that cause heterogeneity in parental disease risks, such as birth cohort or ancenstry admixture, can be adjusted using a stratified log-rank score [7]. ...
Both maternal and paternal disease history can be important predictors of the risk of common conditions such as heart disease or cancer because of shared environmental and genetic risk factors. Sometimes maternal and paternal history can have remarkably different effects on offspring's status. The results are often affected by how the maternal and paternal disease histories are quantified. We proposed using the log-rank score (LRS) to investigate the separate effect of maternal and paternal history on diseases, which takes parental disease status and the age of their disease onset into account. Through simulation studies, we compared the performance of the maternal and paternal LRS with simple binary indicators under two different mechanisms of unbalanced parental effects. We applied the LRS to a national cohort study to further segregate family risks for heart diseases. We demonstrated using the LRS rather than binary indicators can improve the prediction of disease risks and better discriminate the paternal and maternal histories. In the real study, we found that the risk for stroke is closely related with maternal history but not with paternal history and that maternal and paternal disease history have similar impact on the onset of myocardial infarction.
... However, family history scores taking into account family structure and age of onset, as the FamRS we used, have been shown to be more efficient than only looking at positive family history yes/no or even only disease status in parents 9,11,12,25 . ...
The availability of polygenic scores for type 2 diabetes (T2D) raises the question, whether assessing family history might become redundant. However, family history not only involves shared genetics, but also shared environment. It was the aim of this study to assess the independent and combined effects of one family risk score (FamRS) and a polygenic score (PGS) on prevalent and incident T2D risk in a population-based study from Germany (n = 3071). The study was conducted in 2004/2005 with up to 12 years of follow-up. The FamRS takes into account not only the number of diseased first grade relatives, but also age at onset of the relatives and age of participants. 256 prevalent and additional 163 incident T2D cases were recorded. Prevalence of T2D increased sharply for those within the top quantile of the PGS distribution resulting in an OR of 19.16 (p < 2 × 10–16) for the top 20% compared to the remainder of the population, independent of age, sex, BMI, physical activity and FamRS. On the other hand, having a very strong family risk compared to average was still associated with an OR of 2.78 (p = 0.001), independent of the aforementioned factors and the PGS. The PGS and FamRS were only slightly correlated (r²Spearman = 0.018). The combined contribution of both factors varied with varying age-groups, though, with decreasing influence of the PGS with increasing age. To conclude, both, genetic information and family history are relevant for the prediction of T2D risk and might be used for identification of high risk groups to personalize prevention measures.
... Family history is cheap to record, but its value is limited by small family size and personal knowledge or memory. Despite this, its recognised value is reflected in the continuing proposal of methods [3] which aim to achieve the most accurate estimate of genetic risk based of family history. But the value of family history records is inherently limited, since low disease prevalence implies low frequency of positive family history even for diseases with high heritability [4,5,6] Family history has a high positive predictive value, but a low negative predictive value [5]; i.e., a positive family history can imply a high genetic liability to disease, but negative family history implies very little about genetic liability to disease. ...
AUC based on family history as a prediction of genetic risk.
(0.07 MB PDF)
... In addition to the commonly used binary indicator, we proposed a continuous standardized risk score to incorporate the mother's and father's age at onset of asthma into the risk assessment of maternal and paternal histories. This score, similar to that in Feng et al, 20 yet specific to the complicated survey data, is expected to improve prediction of risk in the second generation. We hypothesize that maternal history may contribute more to the asthma risk of their children than does paternal history and investigate this closely in our study. ...
Purpose
This study aimed to examine the separate effects of maternal and paternal history on the onset of asthma in children and evaluate the relationship between age of asthma onset in parents and risk of asthma in their children.
Methods
We used data from the third National Health and Nutrition Examination Survey. We developed new continuous standardized scores for survey data to quantify parental history that incorporated both the occurrence of asthma and the age at onset, and associated these scores with asthma risk in the children. The association analysis was adjusted for sex and obesity status.
Results
Children with maternal history have elevated asthma risk (hazard ratio of 3.71, 95% CI: 1.19–11.60) than those without, and those whose mothers had earlier age of onset have increased risk of asthma compared to those whose mothers had later age of onset. On the contrary, paternal history had a relatively smaller effect that may be only detectable in larger samples (hazard ratio of 2.17, 95% CI: 0.69–6.79).
Conclusion
Maternal asthma history was strongly associated with the onset of asthma in the second generation, and children whose mother had an earlier age of onset had an increased risk of 3.71. For an approximately 10-year decrease in mother’s age at onset of asthma, the risk of asthma for the offspring increased by 1.37-fold. Using our new risk scores led to smaller standard errors and thus more precise estimates than using a binary indicator.
... In the current study, we used simple definitions of 'parental' and 'family' history as these are frequently used in large population settings. More complex family history 'scores'; incorporating age of disease onset, gender and family structures have been proposed (Feng et al. 2009) and might be considered in future applications of our method. Epigenetics is not specifically accounted for in our framework but will be only one of many factors contributing to shared and unshared environmental components. ...
Family history of diabetes is a major risk factor for type 2 diabetes (T2D), but whether this association derives from shared genetic or environmental factors is unclear. To address this question, we developed a statistical framework that models four components of variance, including known and unknown genetic and environmental factors, using a liability threshold model. Focusing on parental history, we simulated case-control studies with two first-degree relatives for each individual, assuming 50 % genetic similarity and a range of values of environmental similarity. By comparing the association of parental history with T2D in our simulations to case-control studies of T2D nested in the Nurses' Health Study and Health Professionals Follow-up Study, we estimate that first-degree relatives have a correlation of 23 % (95 % CI 15-27 %) in their environmental contribution to T2D liability and that this shared environment is responsible for 32 % (95 % CI 24-36 %) of the association between parental history and T2D, with the remainder due to shared genetics. Estimates are robust to varying model parameter values and our framework can be extended to different definitions of family history. In conclusion, we find that the association between parental history and T2D derives from predominately genetic but also environmental effects.
... Thirdly, our study uses family history as a dichotomous variable and this may also cause misclassification or otherwise limit information, as shown in recent studies which have used a continuous measure. 11,33 Recall bias is also possible due to use of self-reported data, although previous studies have found self-reported history to be reliable for stroke data. 34 Due to early case fatality, sicker individuals could have been excluded because they died before reaching age of inclusion eligibility of REGARDS and thus survivorship bias could also have diluted our study findings. ...
We investigated the association between family history of stroke (FHS) and Life's Simple 7 (LS7), a public health metric defined by the American Heart Association.
Reasons for Geographic and Racial Differences in Stroke is a national population-based cohort of 30,239 blacks and whites, aged 45 years or older, sampled from the US population between 2003 and 2007. Data were collected by telephone, mail questionnaires, and in-home examinations. FHS was defined as any first-degree relative with stroke. Levels of the LS7 components (total cholesterol, blood pressure, fasting glucose, physical activity, diet, smoking, and body mass index) were each coded as poor (0 points), intermediate (1 point), or ideal (2 points) health. Ordinal logistic regression was used to model the data.
Among 20,567 subjects with complete LS7 and FHS data, there were 7702 (37%) participants with an FHS. The mean age of the participants was 64 years. The mean (± standard deviation) overall LS7 score was lower for blacks (6.5 ± 2.0) than that of whites (7.6 ± 2.1). FHS was associated with poorer levels of physiological factors, particularly high blood pressure (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.07-1.19) and inversely associated with behaviors such as smoking (OR, .92; 95% CI, .85-.99).
Our results suggest that screening for FHS can provide an opportunity for earlier detection and management of modifiable risk factors.
Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
... Several authors have reviewed different, more elaborated scores incorporating information on the number, kinship, age and gender of affected family members, and the family size and structure, in order to predict family liability. [23][24][25][26] The various methods, including the simple dichotomous score, have all produced significant predictions of the disorder of interest with only small differences between most of the scores. 25,26 The Dunedin Family Health History Study 25 compared the predictability of different scores for a range of mental health disorders and found the density measures (ie, number or proportion of affected family members, or the Reed's score) 27 to be slightly better for all disorders but only significantly better for those conditions with relatively high prevalences. ...
Psychotic experiences (PE) in individuals of the general population are hypothesized to mark the early expression of the pathology underlying psychosis. This notion of PE as an intermediate phenotype is based on the premise that PE share genetic liability with psychosis. We examined whether PE in childhood was predicted by a family history of mental disorder with psychosis rather than a family history of nonpsychotic mental disorder and whether this association differed by severity of PE. The study examined data on 1632 children from a general population birth cohort assessed at age 11-12 years by use of a semistructured interview covering 22 psychotic symptoms. The Danish national registers were linked to describe the complete family history of hospital-based psychiatric diagnoses. Uni- and multivariable logistic regressions were used to test whether a family history of any mental disorder with psychosis, or of nonpsychotic mental disorder, vs no diagnoses was associated with increased risk of PE in offspring (hierarchical exposure variable). The occurrence of PE in offspring was significantly associated with a history of psychosis among the first-degree relatives (adjusted relative risk [RR] = 3.29, 95% CI: 1.82-5.93). The risk increased for combined hallucinations and delusions (adjusted RR = 5.90, 95% CI: 2.64-13.16). A history of nonpsychotic mental disorders in first-degree relatives did not contribute to the risk of PE in offspring nor did any mental disorder among second-degree relatives. Our findings support the notion of PE as a vulnerability marker of transdiagnostic psychosis. The effect of psychosis in first-degree relatives may operate through shared genetic and environmental factors.
© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
... Genetic factors could be easily incorporated into the liability score [Plomin et al., 2009], although it is unclear how much power would be gained with this approach. Family history could improve estimates of disease risk and liability scores [Campbell et al., 2010; Falconer, 1965; Feng et al., 2009]; however, researchers should a priori decide how family history should be incorporated in the liability model. If the ascertainment strategy is to select cases that have little to no risk but have a family history of disease (and conversely controls who are at high risk of being affected but have no family history of disease), then the directionality of family history should be reversed in the risk model. ...
Next-generation sequencing technologies are making it possible to study the role of rare variants in human disease. Many studies balance statistical power with cost-effectiveness by (a) sampling from phenotypic extremes and (b) utilizing a two-stage design. Two-stage designs include a broad-based discovery phase and selection of a subset of potential causal genes/variants to be further examined in independent samples. We evaluate three parameters: first, the gain in statistical power due to extreme sampling to discover causal variants; second, the informativeness of initial (Phase I) association statistics to select genes/variants for follow-up; third, the impact of extreme and random sampling in (Phase 2) replication. We present a quantitative method to select individuals from the phenotypic extremes of a binary trait, and simulate disease association studies under a variety of sample sizes and sampling schemes. First, we find that while studies sampling from extremes have excellent power to discover rare variants, they have limited power to associate them to phenotype—suggesting high false-negative rates for upcoming studies. Second, consistent with previous studies, we find that the effect sizes estimated in these studies are expected to be systematically larger compared with the overall population effect size; in a well-cited lipids study, we estimate the reported effect to be twofold larger. Third, replication studies require large samples from the general population to have sufficient power; extreme sampling could reduce the required sample size as much as fourfold. Our observations offer practical guidance for the design and interpretation of studies that utilize extreme sampling. Genet. Epidemiol. 35: 236-246, 2011. © 2011 Wiley-Liss, Inc.
... The potential for risk prediction using FH risk scores is shown by scores, such as the 'stratified logrank family score' (SLFS), which incorporates the age of disease onset of family members, gender differences and the relationship among family members (66). ...
Family history (FH) studies have been used to quantify the heritable component of diseases for centuries. Genome-wide association studies (GWAS) in both coronary artery disease (CAD) and stroke have implicated several gene loci in these diseases and have shed light on biological mechanisms, but have not yet yielded fruit in terms of clinical application, partly because of the complexity of gene-gene and gene-environment interactions. Family history studies remain the most accessible way of measuring the inherited component of a disease and they represent the overall interaction between environmental and genetic factors. The current knowledge base for FH of stroke and CAD and disease correlates are evaluated. FH of stroke and CAD are inconsistently recorded in clinical practice, partly because of lack of data regarding family history of stroke and CAD in prospective population studies. Future FH studies are necessary to characterise the role of FH in prognosis and risk prediction of contemporary populations, but also to guide future studies of genetics and epigenetics. In this article, the study design and methodology of family history studies are reviewed. The Oxford Vascular Study (OXVASC) is an ongoing prospective, population-based study of CAD and stroke with very high levels of clinical ascertainment, which allows detailed study of FH, and has already shown important new findings. Such data may help to formulate improved risk prediction tools and to inform future GWAS.
... For each participant, an index of family risk was calculated separately for MI and for stroke using the stratified log-rank family score (SLFS). 20 The SLFS provides a single measure of the "severity" of the family risk incorporating age of onset of family members, gender differences, and relationship among family members. SLFSs incorporate both genetic and environmental contributions to family risk and thus do not directly measure heritability. ...
Familial transmission of stroke and myocardial infarction (MI) is partially mediated by transmission of cerebrovascular and cardiovascular risk factors. We examined relationships between family risk of stroke and MI with risk factors for these phenotypes.
A cross-sectional association between the stratified log-rank family score for stroke and MI with prevalent risk factors was assessed in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.
Individuals in the fourth quartile of stratified log-rank family scores for stroke were more likely to have prevalent risk factors including hypertension (OR, 1.43; 95% CI, 1.30-1.58), left ventricular hypertrophy (OR, 1.42; 95% CI, 1.16-1.42), diabetes (OR, 1.26; 95% CI, 1.12-1.43), and atrial fibrillation (OR, 1.23; 95% CI, 1.03-1.45) compared with individuals in the first quartile. Likewise, individuals in the fourth quartile of stratified log-rank family scores for MI were more likely to have prevalent risk factors including hypertension (OR, 1.57; 95% CI, 1.27-1.94) and diabetes (OR, 1.29; 95% CI, 1.12-1.43) than the first quartile. In contrast to stroke, the family risk score for MI was associated with dyslipidemia (OR, 1.38; 95% CI, 1.23-1.55) and overweight/obesity (OR, 1.22; 95% CI, 1.10-1.37).
Family risk of stroke and MI is strongly associated with the majority of risk factors associated with each disease. Family history and genetic studies separating nonspecific contributions of intermediate phenotypes from specific contributions to the disease phenotype may lead to a more thorough understanding of transmission for these complex disorders.
Parental history of cardiovascular disease (CVD) is an independent risk factor for offspring CVD. Patients with chronic plaque psoriasis have an intermediate risk of developing CVD. Objective: To investigate the prevalence of parental history of CVD in patients with psoriasis.
A cross-sectional study on 236 adult patients with chronic plaque psoriasis and 246 controls was performed. Parental history of myocardial infarction and/or stroke was investigated by using a structured questionnaire. The accuracy of the self-reported information was confirmed by the hospital registry.
A positive parental history of maternal myocardial infarction was observed in 28/236 cases compared to 16/246 controls (11.8 vs. 6.5%; p = 0.04). A positive parental history of premature maternal myocardial infarction (i.e. <65 years) was observed in 16/236 cases compared to 3/246 controls (6.8 vs. 1.2%; p = 0.01). Moreover, a positive parental history of paternal stroke was observed in 25/236 cases compared to 14/246 controls (10.5 vs. 5.6%; p = 0.04). A positive parental history of psoriasis was higher in cases than in controls (35 vs. 2%; p < 0.001).
Parental history of CVD could also be investigated in patients with psoriasis for a more comprehensive estimation of their cardiovascular risk.
Although genome-wide association studies have identified markers that are associated with various human traits and diseases, our ability to predict such phenotypes remains limited. A perhaps overlooked explanation lies in the limitations of the genetic models and statistical techniques commonly used in association studies. We propose that alternative approaches, which are largely borrowed from animal breeding, provide potential for advances. We review selected methods and discuss the challenges and opportunities ahead.
For many multifactorial diseases, aetiology is poorly understood. A major research aim is the identification of disease predictors (environmental, biological, and genetic markers). In order to achieve this, a two-stage approach is proposed. The initial or synthesis stage combines observed pedigree data with previous genetic epidemiological research findings, to produce estimates of pedigree members' disease risk and predictions of their disease liability. A further analysis stage uses the latter as inputs to look for associations with potential disease markers. The incorporation of previous research findings into an analysis should lead to power gains. It also allows separate predictions for environmental and genetic liabilities to be generated. This should increase power for detecting disease predictors that are environmental or genetic in nature. Finally, the approach brings pragmatic benefits in terms of data reduction and synthesis, improving comprehensibility, and facilitating the use of existing statistical genetics tools. In this article we present a statistical model and Gibbs sampling approach to generate liability predictions for multifactorial disease for the synthesis stage. We have implemented the approach in a software program. We apply this program to a specimen disease pedigree, and discuss the results produced, comparing its results with those generated under a more naïve model. We also detail simulation studies that validate the software's operation.
The purpose of this study is to assess the impact of family history on the risk of developing breast cancer.
A case-control study design was used.
To provide a comprehensive assessment of family history risk, we used the Utah Population Database, a linked database compiled of genealogy data of the descendants of Mormon pioneer families, cancer data from the Utah Cancer Registry, and mortality data from the Utah Department of Vital Statistics.
All women diagnosed with breast cancer who were in the genealogy database and the Utah Cancer Registry were included. Controls were women selected from the genealogy, who like cases had no record of previous cancer. They were matched to the cases by age and place of birth.
Several definitions of family history were used. The total familial risk variable, developed to work effectively in the Utah Genealogy Database, accounts for all family members, their degree of relatedness to the case, and the amount of time they were observed for possible cancer diagnosis.
A threefold increase in risk, estimated by the odds ratio (OR), of breast cancer among those with the highest family history score (6% of cases) was observed when compared with those with the lowest family history score. The OR for women with a first-degree relative with breast cancer was 2.45 (95% confidence interval [CI], 1.84 to 3.06). If the nearest relative was a second-degree relative, the OR was 1.82 (95% CI, 1.39 to 2.24); if the nearest relative was a third-degree relative, the OR was 1.35 (95% CI, 1.07 to 1.64). A slightly greater risk was observed if the first-degree relative was a woman's mother (OR, 2.44; 95% CI, 1.77 to 3.42) rather than a sister (OR, 2.01; 95% CI, 1.66 to 2.43). Among subjects diagnosed before the age of 50 years, the disease experience of relatives prior to age 50 was most important, while for older subjects the experience of relatives of all ages was of roughly equal importance. Women who developed contralateral breast cancer within 3 years of initial diagnosis were nearly 10 times as likely as women without breast cancer to have a first-degree relative with breast cancer. Based on the risk estimates in this study, we have estimated that approximately 17% to 19% of breast cancer in the population could be attributed to family history. Women who had a first-degree relative with colon cancer had a 30% increased risk of breast cancer.
In this study population, women with a family history of breast cancer, even if the nearest relative with breast cancer is a third-degree relative, are at increased risk of the disease.
A consistent predictor of a woman's risk for breast cancer is a family history of the disease. Most studies of family history and breast cancer have used the number of affected relatives in the family to calculate relative risk, but they have not considered the heterogeneity of the familial risk for breast cancer in a systematic way. With the use of data from a large prospective mortality study of US adults, the authors compared simple classification of family history of breast cancer (yes/no) to the method of using a quantitative family history score method, which takes into account the effects of family structure, age, and birth cohort as predictors of breast cancer mortality. After 9 years of follow-up, 1,428 cases of fatal breast cancer were observed among 453,073 women with complete information on number and age of siblings and family history. With the use of the family history score, about one-third of women with a positive family history of breast cancer were at no higher risk for breast cancer mortality than those without a family history of the disease. As a quantitative measure of relative risk for each family, family history score gave a better fit to the data, and it provided an incremental improvement of predictive accuracy of developing fatal breast cancer. Family history score can also be used as a categorical variable to stratify families. This allows researchers to focus on which risk groups would benefit from conducting further genetic analysis and to test the effects of genetic factors, environmental exposure, and gene-environment interactions on the etiology of the development of breast cancer.
The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 African-American and white adults aged > or =45 years. The objective is to determine the causes for the excess stroke mortality in the Southeastern US and among African-Americans. Participants are randomly sampled with recruitment by mail then telephone, where data on stroke risk factors, sociodemographic, lifestyle, and psychosocial characteristics are collected. Written informed consent, physical and physiological measures, and fasting samples are collected during a subsequent in-home visit. Participants are followed via telephone at 6-month intervals for identification of stroke events. The novel aspects of the REGARDS study allow for the creation of a national cohort to address geographic and ethnic differences in stroke.
Objective.
—The purpose of this study is to assess the impact of family history on the risk of developing breast cancer.
The use of general linear modeling (GLM) procedures based on log-rank scores is proposed for the analysis of survival data and compared to standard survival analysis procedures. For the comparison of two groups, this approach performed similarly to the traditional log-rank test. In the case of more complicated designs - without ties in the survival times - the approach was only marginally less powerful than tests from proportional hazards models, and clearly less powerful than a likelihood ratio test for a fully parametric model; however, with ties in the survival time, the approach proved more powerful than tests from Cox's semi-parametric proportional hazards procedure. The method appears to provide a reasonably powerful alternative for the analysis of survival data, is easily used in complicated study designs, avoids (semi-)parametric assumptions, and is quite computationally easy and inexpensive to employ.
The authors have assembled detailed family histories of cancer on 857 cancer probands, of whom 180 manifested colorectal carcinoma. This study determines if some families had a greater risk for colorectal cancer than others, and if so, what factors were associated with an increase in risk. To test for the possibility of heterogeneity of risk, a parameter called the Z-score, was calculated for each family. The Z-score is a measure of the number of cancer cases in the family adjusted for the number of expected cases. A permutation test was employed to test whether or not the variance of Z-scores from the sample was greater then expected by random chance. The variance for families ascertained through colon cancer probands, but not in any of the other groups, was significantly increased. Of the colon group, 10.6% fell into a high-risk category, as did 5.56% of the rectal cancer families, but only 3.95% of the other groups combined were at high risk. Anatomic sites (in the proband) with the highest Z-score variances were sigmoid and transverse colon, whereas lower variances were seen for cecum and descending colon. Risk status therefore may be partially dependent upon exact anatomic sites within the colon. The effect of proband's age of diagnosis was not significant, but did show the possibility of an effect on heterogeneity of risk for both the younger and older groups.
SUMMARY The asymptotic distributions of camér-von Mises type statistics based on the productlimit estimate of the distribution function
of a certain class of randomly censored observations are derived; the asymptotic significance points of the statistics for
various degrees of censoring are given. The statistics are also partitioned into orthogonal components in the manner of Durbin
& Knott (1972). The asymptotic powers of the statistics and their components against normal mean and variance shifts, exponential
scale shifts, and Weibull alternatives to exponentiality are compared. Data arising in a competing risk situation are examined,
using the Cramér-von Mises statistic.
Cancer family history was quantified in 229 subjects (122 female, 107 male) screened for total serum cholesterol as seventh graders in 1972-1973 and repeated nine years later as young adults. Division of the subjects on the basis of cholesterol quintile resulted in significantly lower cancer family history scores in participants with persistently low total serum cholesterol levels and a significant excess of cancer mortality in parents and grandparents of young adult males with high-density lipoprotein (HDL) levels in the upper quintile. A trend toward increased cancer in families of young adults who were smokers was independent of the cholesterol levels. It is suggested that such a quantification of family history score will be more useful than simply designating the family history as positive or negative in future modeling schemes for predicting risk.
The relative risk of developing future coronary heart disease (CHD) or hypertension between positive and negative family history families is compared for different definitions of a positive family history when applied to life-table data for 94,292 persons. Having two or more first degree relatives with CHD identifies 8% of the population with relative risks of 3.3-5.9 for CHD before age 50. A quantitative family history score (FHS) compares the family's age and sex specific disease incidence to that expected in the general population and predicts future disease incidence in unaffected family members slightly better (relative risks = 3.4-6.9 for CHD before age 50). Using only one affected relative, even if affected at an early age (less than 55 years old) does not discriminate low and high risk families as well (relative risks = 1.4-3.9 for CHD before age 50). Similar results were obtained for family history of hypertension. There is an increase in future disease incidence for all ages with increasing FHS values (p less than 0.0001), which can be used as a continuous or categorical variable in analysis where family history is associated with a particular variable under study. These results provide a rational basis for choosing and applying specific definitions of a positive family history of coronary disease or hypertension in clinical, epidemiologic and genetic studies.
Among 121,964 women aged 30-55 years in 1976, 117,156 who were initially free from coronary heart disease provided information on a number of coronary risk factors including parental history of myocardial infarction and were followed prospectively. In 1976, 31,101 (26.5%) reported that at least one parent had suffered a myocardial infarction. Questionnaires in 1978 and 1980 identified women who had developed nonfatal myocardial infarction (n = 132) and angina pectoris (n = 101). Fatal coronary heart disease cases (n = 42) were ascertained by searches of state vital records. The age-adjusted relative risk of nonfatal myocardial infarction for women with a parental history of myocardial infarction less than or equal to 60 years of age compared with women with no family history was 2.8 (95% confidence limits (CL) 1.8, 4.3). For those with a parental history of myocardial infarction greater than 60 years of age, the age-adjusted relative risk of nonfatal myocardial infarction was 1.0 (CL 0.5, 1.8). The age-adjusted relative risks of fatal coronary heart disease were 5.0 (CL 2.7, 9.2) for parental history before age 61 and 2.6 (CL 1.1, 5.8) for parental history after age 60. The corresponding relative risks of angina pectoris were 3.4 (CL 2.2, 5.2) and 1.9 (CL 1.2, 3.2), respectively. These associations were only slightly altered by adjustment for history of hypertension, diabetes, high cholesterol, use of oral contraceptives, menopause, postmenopausal hormone use, obesity, or smoking, in individual stratified analysis or in multivariate analyses. These data support the hypothesis that parental history of myocardial infarction has an independent effect on risk that is not explained solely by individual risk factors.
The authors have assembled detailed family histories of cancer on 857 cancer probands, of whom 180 manifested colorectal carcinoma. This study determines if some families had a greater risk for colorectal cancer than others, and if so, what factors were associated with an increase in risk. To test for the possibility of heterogeneity of risk, a parameter called the Z-score, was calculated for each family. The Z-score is a measure of the number of cancer cases in the family adjusted for the number of expected cases. A permutation test was employed to test whether or not the variance of Z-scores from the sample was greater then expected by random chance. The variance for families ascertained through colon cancer probands, but not in any of the other groups, was significantly increased. Of the colon group, 10.6% fell into a high-risk category, as did 5.56% of the rectal cancer families, but only 3.95% of the other groups combined were at high risk. Anatomic sites (in the proband) with the highest Z-score variances were sigmoid and transverse colon, whereas lower variances were seen for cecum and descending colon. Risk status therefore may be partially dependent upon exact anatomic sites within the colon. The effect of proband's age of diagnosis was not significant, but did show the possibility of an effect on heterogeneity of risk for both the younger and older groups.
It is often of interest to know whether there is increased occurrence of a trait in a pedigree or other structured set of epidemiological data. In answering such questions most current methods use aggregate measures, such as relative risk, that may not relate the outcome for each individual to that individual's risk. In this paper we present a simple method, and its computational algorithm, to overcome this limitation. This new method also permits one to identify high‐risk families or subsets of a collection of data, which is not always possible using other approaches.
In a study of cancer risk among relatives of retinoblastoma patients, by applying this new method it was found that 11 of 33 families each obtained through a unilateral retinoblastoma patient are at statistically high risk of cancer at all sites combined, while there are 15 of 47 such families obtained through a bilaterally affected proband. These results are unlikely to have occured by chance, indicating an overall excess risk in the ancestors of these retinoblastoma cases.
The proposed test procedure does not specify the cause of elevated risk; however, a method is proposed that provides some indication regarding possible causal mechanisms under some circumstances.
The role of the family history as a tool for the diagnosis of inherited thrombophilia has not been established. Several authors have indicated that a positive family history is not a good predictor of inherited abnormalities such as antithrombin III deficiency, or deficiencies of protein C or protein S. We have tried to approach the family history in a quantitative way. To this end we used the cumulative incidence data of thrombosis in the general population and also in a population of protein C deficient families to estimate the expected number of symptomatic subjects in a family under both the hypothesis of inherited thrombophilia and the null-hypothesis. Although a number of assumptions underlying our calculations need to be verified and probably adjusted before any truly quantitative meaning can be assigned to this approach, we feel that the family history is a useful diagnostic test for inherited thrombophilia if it is used in a critical way.
The role of genetics in cerebrovascular disease remains controversial. The purpose of this study was to assess the influence of family history on atherothrombotic infarction or transient ischemic attack.
Ninety patients with stroke or transient ischemic attack and 90 age- and sex-matched community control subjects were studied prospectively. Medical and family histories were obtained from all subjects, and a complete physical examination was performed.
Eighty-five patients and 86 control subjects knew their family history for ischemic heart disease and stroke. A positive history for ischemic heart disease was present in 62 (73%) of the patients and 46 (53%) of the control subjects (P = .019), and a positive family history for stroke was present in 38 (47%) of the patients and 21 (24%) of the control subjects (P = .014).
Although a positive vascular family history was not an independent risk factor in a multivariate analysis, it was an excellent marker of the presence of other established vascular risk factors. Personal histories of ischemic heart disease, hypertension, and hyperlipidemia were found to be significant independent risk factors for stroke.
It has been suggested that a family history positive for coronary heart disease (CHD) increases the risk of CHD. We studied this association to determine the degree of risk, the independence of this association and the presence of interaction of a family history of CHD with the major known risk factors in a law incidence area.
One hundred and six hospital cases (85 males and 21 females) of CHD and 106 hospital controls individually matched with each case for sex, age and place of residence (rural–urban) were studied. From every participant, information was collected on their personal and family history of cardiovascular disease and risk factors; height, weight, lipid profile and blood pressure were measured, and an electrocardiogram was recorded. Conditional logistic regression was used in the analysis.
The observed odds ratio of patients suffering from CHD among those with, compared to those without, a positive family history of CHD was 4.95 (95. confidence interval = 1.27–19.28) after adjusting for the major known risk factors in each individual and their families (no interaction term remained in the model).
The results support the hypothesis that a family history of CHD, acting through mechanisms other than known risk factors or their familial aggregation, is an independent risk factor for CHD even in a low incidence area. No interaction effect was observed between family history and the presence of the three major risk factors of CHD. This should help to identify individuals at greater risk of CHD.
We were interested in studying whether a family history of coronary heart disease (CHD) persisted as a significant risk factor for premature coronary heart disease after adjusting for traditional and nontraditional risk factors.
Ninety-five case patients with documented premature CHD (occurring in a person less than 60 years old and with greater than 50 percent occlusion of a major epicardial vessel or a documented myocardial infarction) and 95 community-based control patients were examined for risk factors including family history, hypertension, diabetes mellitus, sedentary lifestyle, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol, lipoprotein(a), homocysteine, and fibrinogen.
The risk of premature CHD for a positive family history ranged from an odds ratio (OR) of 3.25 for a standard family history of CHD in a first-degree relative, 5.9 for family history of early CHD in a first-degree relative before the age of 45 years, and 6.1 for a strong family history of CHD defined as CHD in at least two first-degree relatives. Family history persisted as a significant risk factor for premature CHD (OR = 3.9, 95 percent confidence interval [CI] 1.8-8.7) in multiple variable models that included traditional and nontraditional risk factors. It was rare, however, for a person with a positive family history not to have at least two other traditional or nontraditional risk factors.
Family history of CHD should not be considered a simple binary risk factor for premature CHD, and a positive family history of CHD indicates that a person is at high risk for premature CHD independent of traditional and nontraditional risk factors.
Available data show that women tend to overestimate their risk of developing breast cancer. Available models allow for the rapid identification of women who are at increased risk for breast cancer, along with a quantitative estimate of their probability of developing breast cancer over a period of years or by a certain age. Important risk factors include age; family history of breast cancer in first-degree (mother, sister, or daughter) or second-degree (aunt or grandmother) relatives; history of biopsy for benign breast disease, with or without atypical hyperplasia; nulliparity or first live birth after age 30; and menarche before age 12. Risk should be quantified routinely when women seek advice about breast cancer risk-management strategies. Counseling, with appropriate referrals when required, should always accompany specific recommendations for managing risk. Additional predictive models are needed for nonwhite women and for women not being screened regularly with mammography.
Family history serves as the most important risk factor in prevention of coronary heart disease from youth. Prevalent methods of assessing family history, however, have serious drawbacks: a sudden rise of risk when a family member develops the disease; insufficient control for age among family members. We propose a simple quantitative method overcoming such drawbacks. Data on family history were obtained by questionnaires sent to 2,393 male high school students and their cholesterol levels were measured. Family risk from each family member was calculated by (30/Risk age)4, where the risk age was age at onset expressed by decade; if absent, it was replaced by present age or age at death. A mean score in a family served as the family risk. A total of 1,584 students and 17,127 family members were analyzed. The proposed method yielded a statistically significant association (Odds ratio = 1.60; 95% confidence interval: 1.15-2.25) between the family risk (above or below the median) and the student's atherogenic index (above or below the 90th percentile) calculated from cholesterols. This association was stronger than those by conventional methods. The proposed method may be useful in prevention activities and its efficiency needs to be confirmed in other studies.
The purpose of this study was to call attention to a potential bias or misclassification resulting from disregarding sex and age of family members in assessing family history of hypertension. Family history of hypertension was obtained among 23,803 family members through a questionnaire survey of 2,316 high school students. From the obtained data sex- and age-specific proportion of a positive history of hypertension was calculated. The effects of sex and age on a positive history was assessed by the logistic regression analysis of the family history. Below age 70 the odds ratios for sex difference were at least 1.24 (p < 0.05) and odds ratios for age difference were at least 1.05 (p < 0.05). This indicated that below age 70 male members had a positive history at least 1.24 times more frequently than females of the same age, and that a positive history increased by at least (1.05)y, where y was age difference by year. Above age 70 the odds ratios for sex and age differences were small. A potential bias or misclassification resulting from sex and age difference can be substantial below age 70. Some measures to control for sex and age of family members are required in assessing the family history.
We examined 15 published continuous family history measures (scores) as well as two new formulations in terms of several desirable properties. We applied the scores to sample pedigrees and found that some systematically increase with family size. In contrast to aggregate scores, non-aggregate scores are sensitive to the age, sex, and covariate status of individual relatives but are unstable when the families are small. We also applied these scores to our own population case-control data, characterised by a high proportion of missing and false-negative responses. In these small families, all scores provided significant discrimination between CHD cases and controls beyond the usual categorical definition of positive family history, but appeared no better than detailed categorical definitions or even simple counts. Our new formulations offer no solution to the problems of few data; most scores apply asymptotic approximations to differences between observed and expected number of affected relatives and are not suited to small families. All scores would be improved by ruling out families with only one affected relative, as is being done in the NHLBI Family Heart Study. We recommend that researchers, when using a family history measure, consider the number of informative families and other characteristics of their data prior to choosing any particular formulation.
Family history of coronary heart disease (CHD) has been found to be a risk factor for CHD in numerous studies. Few studies have addressed whether a quantitative measure of family history of CHD (family risk score, FRS) predicts CHD in African Americans. This study assessed the association between FRS and incident CHD of participants, and the variation of the association by gender and race. Participants in the study were a biracial population-based cohort with 3,958 African Americans and 10,580 Whites aged 45-64 years old in the ARIC baseline survey (1987-1989). They were randomly selected from four U. S. communities. During follow-up (1987-1993), 352 participants experienced the onset of CHD. Incidence density of CHD (per 1,000 person-years) was 7.8 and 3.6 among African-American men (AAM) and women (AAW), and 7.2 and 2.2 among White men (WM) and women (WW). The hazard rate ratio (HRR) of CHD associated with one standard deviation increase of FRS was 1.52 in AAW, 1.46 in AAM, 1.41 in WW, and 1.68 in WM. The HRRs decreased 4.6% in AAW, 1.4% in WW, 5.7% in AAM, and 3.0% in WM, but increased 2.1% in AAM after adjustment for selected covariates. FRS predicts incident CHD in African Americans and Whites, men and women. The relation of FRS to incident CHD can be only partially explained by the selected risk factors in the biological causal pathways: IMT, T-G, LDL, HDL, Lp(a), fibrinogen and hypertension. No significant difference by race has been found in this study.
Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.
We explored the relation between family history of coronary heart disease and the risk of myocardial infarction in a case-control study of subjects, 45 to 70 years of age, living in Stockholm, Sweden. Our cases comprised 1091 male and 531 female first-time acute myocardial infarction patients who had survived at least 28 days after their infarction. Referents were randomly selected from the population from which the cases were derived. The adjusted odds ratio (OR) of myocardial infarction was 2.0 (95% confidence interval [CI] = 1.6-2.6) for men reporting > or = 1 affected parent or sibling, compared with men with no family history of coronary heart disease, and 3.4 (95% CI = 2.1-5.9) for those reporting > or = 2 affected parents or siblings. The corresponding OR for women were 2.1 (95% CI = 1.5-3.0) and 4.4 (95% CI = 2.4-8.1). We found evidence for synergistic interactions in women exposed to family history of coronary heart disease in combination with current smoking and with a high quotient between low-density lipoprotein and high-density lipoprotein cholesterol (>4.0), respectively, which yielded adjusted synergy index scores of 2.9 (95% CI = 1.2-7.2) and 3.8 (95% CI = 1.5-9.7), respectively. Similarly, in men we found evidence for interaction for the co-exposure of family history of coronary heart disease and diabetes mellitus. Our study shows that family history of coronary heart disease is not only a strong risk factor for myocardial infarction in both sexes, but that its effect is synergistic with other cardiovascular risk factors as well.
The relation between a family history of heart attack and the occurrence of early myocardial infarction (MI) has not been studied extensively in women. In addition, whether recognized and newly-identified coronary heart disease (CHD) risk factors account for the familial aggregation of these events remains unknown. We therefore examined these questions in a population-based case-control study among female 18- to 44-year-old residents of western Washington State.
The patients consisted of 107 women with first acute MI, and the control subjects comprised 526 women similar in age identified from the community and without a history of recognized clinical coronary heart disease or stroke. Trained interviewers used a structured questionnaire to elicit a detailed history of heart attack in first-degree relatives. Information about other known MI risk factors was collected and biochemical measurements performed, and common polymorphisms in various candidate genes were determined. The rate of MI among first-degree relatives of MI cases was twice as high as among first-degree relatives of controls (relative risk, 1.96; 95% confidence interval (CI), 1.46-2.48); this association was present for each familial relationship. Sibling history of MI but not parental history was associated with MI, after controlling for established CHD risk factors. In a subsample of subjects with blood measurements, further adjustment for lipids, lipoproteins and specific genetic risk factors slightly reduced the association with sibling MI history (from odds ratio (OR), 5.17; 95% CI, 1.93-13.85 to OR, 3.97; 95% CI, 0.92-17.17).
Family history of MI is positively associated with the risk of early MI in women. While the association with parental history of MI is mediated through the clustering of other common risk factors, the association of sibling history of MI with early-onset MI in young women is only partially explained by the clustering of established and newly-identified risk factors.
Few studies have examined the effects of paternal and maternal history of myocardial infarction (MI), including age at MI, on cardiovascular disease (CVD) risk, particularly among women.
We prospectively studied 22 071 men from the Physicians' Health Study and 39 876 women from the Women's Health Study with data on parental history and age at MI. Among men, 2654 CVD cases developed over 13.0 years; among women, 563 CVD cases occurred over 6.2 years. Compared with men with no parental history, only maternal, only paternal, and both maternal and paternal history of MI conferred relative risks (RRs) of CVD of 1.71, 1.40, and 1.85; among women, the respective RRs were 1.46, 1.15, and 2.05. For men, maternal age at MI of <50, 50 to 59, 60 to 69, 70 to 79, and >/=80 years had RRs of 1.00, 1.88, 1.88, 1.67, and 1.17; for women, the RRs for maternal age at MI of <50, 50 to 59, and >/=60 years were 2.57, 1.33, and 1.52. Paternal age at MI of <50, 50 to 59, 60 to 69, 70 to 79, and >/=80 years in men had RRs of 2.19, 1.64, 1.42, 1.16, and 0.92; in women, for paternal age at MI of <50, 50 to 59, and >/=60 years, the RRs were 1.63, 1.33, and 1.13.
An early history of parental MI (<60 years) conferred a greater risk of CVD than did MI at older ages. However, an increased risk of CVD remained for maternal age at MI of 70 to 79 years in men and >/=60 years in women, which suggests that any maternal history of MI may be important.
To assess the contribution of family history of coronary heart disease (CHD) and longevity in parents to 5-year incidence of coronary events in middle-aged men.
A prospective study in men from Northern Ireland and the French cities and environs of Lille, Strasbourg, and Toulouse. A total of 10 600 men aged 50-59 years were examined between 1991 and 1994 and followed annually by questionnaire for incident cases of coronary disease. A detailed family history was taken and a quantitative family risk score for CHD was calculated for each subject. Five-year follow-up is complete; all coronary events (coronary deaths, myocardial infarction, and angina) documented by clinical records were reviewed by an independent medical committee.
At screening, 9758 subjects were free of clinical and historical evidence of CHD; in this group there were 317 coronary events by 5 years of follow-up. Subjects whose parents had both survived until >/=80 years showed a relative odds of 0.49 (95% CI: 0.31-0.77) for risk of a coronary event compared with subjects whose parents had not survived until >/=80 years old with adjustment for age and nine other risk factors including family history. The pattern of results was similar in France and Northern Ireland, although parental survival was longer in France. Likewise, subjects with a strong family history showed a relative odds of 1.93 (95% CI: 1.25-3.00) compared with subjects without such a history, after adjustment for age and the nine risk factors including parental longevity. The pattern of results was similar in France and Northern Ireland.
These results indicate that a family history of coronary disease and parental longevity, although related, act independently of one another and of other major cardiovascular risk factors in predicting 5-year risk of subsequent coronary events.
In medical research, continuous variables are often converted into categorical variables by grouping values into two or more categories. We consider in detail issues pertaining to creating just two groups, a common approach in clinical research. We argue that the simplicity achieved is gained at a cost; dichotomization may create rather than avoid problems, notably a considerable loss of power and residual confounding. In addition, the use of a data-derived 'optimal' cutpoint leads to serious bias. We illustrate the impact of dichotomization of continuous predictor variables using as a detailed case study a randomized trial in primary biliary cirrhosis. Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models.
Despite improved understanding of atherothrombosis, cardiovascular prediction algorithms for women have largely relied on traditional risk factors.
To develop and validate cardiovascular risk algorithms for women based on a large panel of traditional and novel risk factors.
Thirty-five factors were assessed among 24 558 initially healthy US women 45 years or older who were followed up for a median of 10.2 years (through March 2004) for incident cardiovascular events (an adjudicated composite of myocardial infarction, ischemic stroke, coronary revascularization, and cardiovascular death). We used data among a random two thirds (derivation cohort, n = 16 400) to develop new risk algorithms that were then tested to compare observed and predicted outcomes in the remaining one third of women (validation cohort, n = 8158).
Minimization of the Bayes Information Criterion was used in the derivation cohort to develop the best-fitting parsimonious prediction models. In the validation cohort, we compared predicted vs actual 10-year cardiovascular event rates when the new algorithms were compared with models based on covariates included in the Adult Treatment Panel III risk score.
In the derivation cohort, a best-fitting model (model A) and a clinically simplified model (model B, the Reynolds Risk Score) had lower Bayes Information Criterion scores than models based on covariates used in Adult Treatment Panel III. In the validation cohort, all measures of fit, discrimination, and calibration were improved when either model A or B was used. For example, among participants without diabetes with estimated 10-year risks according to the Adult Treatment Panel III of 5% to less than 10% (n = 603) or 10% to less than 20% (n = 156), model A reclassified 379 (50%) into higher- or lower-risk categories that in each instance more accurately matched actual event rates. Similar effects were achieved for clinically simplified model B limited to age, systolic blood pressure, hemoglobin A(1c) if diabetic, smoking, total and high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and parental history of myocardial infarction before age 60 years. Neither new algorithm provided substantive information about women at very low risk based on the published Adult Treatment Panel III score.
We developed, validated, and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40% to 50% of women at intermediate risk into higher- or lower-risk categories.
Quantification of familial predisposition to disease
- Groeneveld Ht
- Hitzeroth
- Hw
Groeneveld HT, Hitzeroth HW. Quantification of familial predisposition to disease. South African Statistical Journal 1991; 25(1):45–60.
National Institute of Neurological Disorders and Stroke, National Institutes of Health (funding agency): Claudia Moy PhD
- Frederick Unverzagt
Frederick Unverzagt PhD; National Institute of Neurological Disorders and Stroke, National Institutes of Health (funding agency): Claudia Moy PhD. REFERENCES
Quantification of familial predisposition to disease
- Groeneveld HT
Groeneveld HT, Hitzeroth HW. Quantification of familial predisposition to disease. South African
Statistical Journal. 1991; 25(1):45-60.
Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women
- Sesso