Risk markers including coronary artery calcium, carotid intima-media thickness, ankle-brachial index, brachial flow-mediated dilation, high-sensitivity C-reactive protein (CRP), and family history of ...coronary heart disease (CHD) have been reported to improve on the Framingham Risk Score (FRS) for prediction of CHD, but there are no direct comparisons of these markers for risk prediction in a single cohort.
We compared improvement in prediction of incident CHD/cardiovascular disease (CVD) of these 6 risk markers within intermediate-risk participants (FRS >5%-<20%) in the Multi-Ethnic Study of Atherosclerosis (MESA).
Of 6814 MESA participants from 6 US field centers, 1330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002, with follow-up through May 2011. Probability-weighted Cox proportional hazard models were used to estimate hazard ratios (HRs). Area under the receiver operator characteristic curve (AUC) and net reclassification improvement were used to compare incremental contributions of each marker when added to the FRS, plus race/ethnicity.
Incident CHD defined as myocardial infarction, angina followed by revascularization, resuscitated cardiac arrest, or CHD death. Incident CVD additionally included stroke or CVD death.
After 7.6-year median follow-up (IQR, 7.3-7.8), 94 CHD and 123 CVD events occurred. Coronary artery calcium, ankle-brachial index, high-sensitivity CRP, and family history were independently associated with incident CHD in multivariable analyses (HR, 2.60 95% CI, 1.94-3.50; HR, 0.79 95% CI, 0.66-0.95; HR, 1.28 95% CI, 1.00-1.64; and HR, 2.18 95% CI, 1.38-3.42, respectively). Carotid intima-media thickness and brachial flow-mediated dilation were not associated with incident CHD in multivariable analyses (HR, 1.17 95% CI, 0.95-1.45 and HR, 0.95 95% CI, 0.78-1.14). Although addition of the markers individually to the FRS plus race/ethnicity improved AUC, coronary artery calcium afforded the highest increment (0.623 vs 0.784), while brachial flow-mediated dilation had the least (0.623 vs 0.639). For incident CHD, the net reclassification improvement with coronary artery calcium was 0.659, brachial flow-mediated dilation was 0.024, ankle-brachial index was 0.036, carotid intima-media thickness was 0.102, family history was 0.160 and high-sensitivity CRP was 0.079. Similar results were obtained for incident CVD.
Coronary artery calcium, ankle-brachial index, high-sensitivity CRP, and family history were independent predictors of incident CHD/CVD in intermediate-risk individuals. Coronary artery calcium provided superior discrimination and risk reclassification compared with other risk markers.
Net reclassification indices have recently become popular statistics for measuring the prediction increment of new biomarkers. We review the various types of net reclassification indices and their ...correct interpretations. We evaluate the advantages and disadvantages of quantifying the prediction increment with these indices. For predefined risk categories, we relate net reclassification indices to existing measures of the prediction increment. We also consider statistical methodology for constructing confidence intervals for net reclassification indices and evaluate the merits of hypothesis testing based on such indices. We recommend that investigators using net reclassification indices should report them separately for events (cases) and nonevents (controls). When there are two risk categories, the components of net reclassification indices are the same as the changes in the true- and false-positive rates. We advocate the use of true- and false-positive rates and suggest it is more useful for investigators to retain the existing, descriptive terms. When there are three or more risk categories, we recommend against net reclassification indices because they do not adequately account for clinically important differences in shifts among risk categories. The category-free net reclassification index is a new descriptive device designed to avoid predefined risk categories. However, it experiences many of the same problems as other measures such as the area under the receiver operating characteristic curve. In addition, the category-free index can mislead investigators by overstating the incremental value of a biomarker, even in independent validation data. When investigators want to test a null hypothesis of no prediction increment, the well-established tests for coefficients in the regression model are superior to the net reclassification index. If investigators want to use net reclassification indices, confidence intervals should be calculated using bootstrap methods rather than published variance formulas. The preferred single-number summary of the prediction increment is the improvement in net benefit.
Age in dogs is associated with the risk of many diseases, and canine size is a major factor in that risk. However, the size patterns are complex. While small size dogs tend to live longer, some ...diseases are more prevalent among small dogs. In this study we seek to quantify how the pattern of disease history varies across the spectrum of dog size, dog age, and their interaction. Utilizing owner-reported data on disease history from a substantial number of companion dogs enrolled in the Dog Aging Project, we investigate how body size, as measured by weight, associates with the lifetime prevalence of a reported condition and its pattern across age for various disease categories. We found significant positive associations between dog size and the lifetime prevalence of skin, bone/orthopedic, gastrointestinal, ear/nose/throat, cancer/tumor, brain/neurologic, endocrine, and infectious diseases. Similarly, dog size was negatively associated with lifetime prevalence of ocular, cardiac, liver/pancreas, and respiratory disease categories. Kidney/urinary disease prevalence did not vary by size. We also found that the association between age and lifetime disease prevalence varied by dog size for many conditions including ocular, cardiac, orthopedic, ear/nose/throat, and cancer. Controlling for sex, purebred vs. mixed-breed status, and geographic region made little difference in all disease categories we studied. Our results align with the reduced lifespan in larger dogs for most of the disease categories and suggest potential avenues for further examination.
Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to ...date, no risk score incorporating CAC has been developed.
The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors.
Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study).
Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate.
An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.
Objectives The purpose of this study was to examine the association of both a low and a high ankle-brachial index (ABI) with incident cardiovascular events in a multiethnic cohort. Background ...Abnormal ABIs, both low and high, are associated with elevated cardiovascular disease (CVD) risk. However, it is unknown whether this association is consistent across different ethnic groups, and whether it is independent of both newer biomarkers and other measures of subclinical atherosclerotic CVD. Methods A total of 6,647 non-Hispanic white, African-American, Hispanic, and Chinese men and women age 45 to 84 years from free-living populations in 6 U.S. field centers and free of clinical CVD at baseline had extensive measures of traditional and newer biomarker risk factors, and measures of subclinical CVD, including the ABI. Incident CVD, defined as coronary disease, stroke, or other atherosclerotic CVD death, was determined over a mean follow-up of 5.3 years. Results Both a low (<1.00) and a high (≥1.40) ABI were associated with incident CVD events. Sex- and ethnic-specific analyses showed consistent results. Hazard ratios were 1.77 (p < 0.001) for a low and 1.85 (p = 0.050) for a high ABI after adjustment for both traditional and newer biomarker CVD risk factors, and the ABI significantly improved risk discrimination. Further adjustment for coronary artery calcium score, common and internal carotid intimal medial thickness, and major electrocardiographic abnormalities only modestly attenuated these hazard ratios. Conclusions In this study, both a low and a high ABI were associated with elevated CVD risk in persons free of known CVD, independent of standard and novel risk factors, and independent of other measures of subclinical CVD. Further research should address the cost effectiveness of measuring the ABI in targeted population groups.
We tested whether objectively measured indices of obstructive sleep apnoea (OSA) and sleep quality are associated with coronary artery calcification (CAC) prevalence independent of obesity, a classic ...confounder.
1465 Multi-Ethnic Study of Atherosclerosis participants (mean age 68 years), who were free of clinical cardiovascular disease, had both coronary CT and in-home polysomnography and actigraphy performed. OSA categories were defined by the Apnea-Hypopnea Index (AHI). Prevalence ratios (PRs) for CAC >0 and >400 (high burden) were calculated.
Participants with severe OSA (AHI ≥30; 14.6%) were more likely to have prevalent CAC, relative to those with no evidence of OSA, after adjustment for demographics and smoking status (PR 1.16; 95% CI 1.06 to 1.26), body mass index (1.11; 1.02 to 1.21) and traditional cardiovascular risk factors (1.10; 1.01 to 1.19). Other markers of hypoxaemia tended to be associated with a higher prevalence of CAC >0. For CAC >400, a higher prevalence was observed with both a higher arousal index and less slow-wave sleep. Overall, associations were somewhat stronger among younger participants, but did not vary by sex or race/ethnicity.
In this population-based multi-ethnic sample, severe OSA was associated with subclinical coronary artery disease (CAC >0), independent of obesity and traditional cardiovascular risk factors. Furthermore, the associations of the arousal index and slow-wave sleep with high CAC burden suggest that higher nightly sympathetic nervous system activation is also a risk factor. These findings highlight the potential importance of measuring disturbances in OSA as well as sleep fragmentation as possible risk factors for coronary artery disease.
Validation of a new coma scale: The FOUR score Wijdicks, Eelco F. M.; Bamlet, William R.; Maramattom, Boby V. ...
Annals of neurology,
October 2005, Letnik:
58, Številka:
4
Journal Article
Recenzirano
The Glasgow Coma Scale (GCS) has been widely adopted. Failure to assess the verbal score in intubated patients and the inability to test brainstem reflexes are shortcomings. We devised a new coma ...score, the FOUR (Full Outline of UnResponsiveness) score. It consists of four components (eye, motor, brainstem, and respiration), and each component has a maximal score of 4. We prospectively studied the FOUR score in 120 intensive care unit patients and compared it with the GCS score using neuroscience nurses, neurology residents, and neurointensivists. We found that the interrater reliability was excellent with the FOUR score (κw = 0.82) and good to excellent for physician rater pairs. The agreement among raters was similar with the GCS (κw = 0.82). Patients with the lowest GCS score could be further distinguished using the FOUR score. We conclude that the agreement among raters was good to excellent. The FOUR score provides greater neurological detail than the GCS, recognizes a locked‐in syndrome, and is superior to the GCS due to the availability of brainstem reflexes, breathing patterns, and the ability to recognize different stages of herniation. The probability of in‐hospital mortality was higher for the lowest total FOUR score when compared with the lowest total GCS score. Ann Neurol 2005;58:585–593
To evaluate the predictive value of abdominal aortic calcium (AAC) for incident cardiovascular disease (CVD) independent of coronary artery calcium (CAC).
We evaluated the association of AAC with CVD ...in 1974 men and women aged 45 to 84 years randomly selected from the Multi-Ethnic Study of Atherosclerosis participants who had complete AAC and CAC data from computed tomographic scans. AAC and CAC were each divided into following 3 percentile categories: 0 to 50th, 51st to 75th, and 76th to 100th. During a mean of 5.5 years of follow-up, there were 50 hard coronary heart disease events, 83 hard CVD events, 30 fatal CVD events, and 105 total deaths. In multivariable-adjusted Cox models including both AAC and CAC, comparing the fourth quartile with the ≤ 50th percentile, AAC and CAC were each significantly and independently predictive of hard coronary heart disease and hard CVD, with hazard ratios ranging from 2.4 to 4.4. For CVD mortality, the hazard ratio was highly significant for the fourth quartile of AAC, 5.9 (P=0.01), whereas the association for the fourth quartile of CAC (hazard ratio, 2.1) was not significant. For total mortality, the fourth quartile hazard ratio for AAC was 2.7 (P=0.001), and for CAC, it was 1.9, P=0.04. Area under the receiver operating characteristic curve analyses showed improvement for both AAC and CAC separately, although improvement was greater with CAC for hard coronary heart disease and hard CVD, and greater with AAC for CVD mortality and total mortality. Sensitivity analyses defining AAC and CAC as continuous variables mirrored these results.
AAC and CAC predicted hard coronary heart disease and hard CVD events independent of one another. Only AAC was independently related to CVD mortality, and AAC showed a stronger association than CAC with total mortality.
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