Idiopathic Pulmonary Fibrosis (IPF) and Sarcoidosis are distinct clinical entities. Fibrotic disease in pulmonary sarcoidosis is typically upper lobe predominant. In IPF fibrosis is basilar and ...peripheral predominant usual interstitial pneumonia (UIP) pattern. Sarcoidosis and UIP have rarely been observed in the same patient. We sought to characterize patients manifesting both sarcoidosis and IPF and compare clinical features and survival to that of patients with “Lone-IPF” (IPF only) and pulmonary sarcoidosis with fibrosis in a non-UIP pattern.
Patients were identified from a clinical database and data abstracted from medical records (1995–2016): 1) 25 patients with combined sarcoidosis and IPF (CSIPF) defined by clinical and histological features of sarcoidosis and HRCT features of possible or definite UIP or UIP by histopathology; 2) Randomly selected control patients during the same period: 28 Lone-IPF, 25 stage III/IV pulmonary sarcoidosis.
The gender and race of patients with CSIPF and Lone-IPF patients were similar (68% male and 84% Caucasian), as were survival outcomes. Mean time from IPF diagnosis to death: 3.2 years CSIPF, 3.6 years Lone-IPF (log rank p value 0.49). Among patients with pulmonary sarcoidosis, mean time from diagnosis to death: 21.4 years.
Clinical characteristics/behavior of patients with CSIPF was similar to Lone-IPF patients. It is possible that patients with sarcoidosis coincidentally developed IPF and/or have occult genetic predisposition factors to manifest both diseases at different time points. Further study is needed.
Subclinical atherosclerosis (SA) diagnosis is key to primary prevention of atherosclerotic cardiovascular disease (ASCVD). SA is common among diabetics. Ankle brachial index (ABI) and coronary artery ...calcium (CAC) are markers of SA. This study examined whether adding ABI and CAC to diabetic individuals improved ASCVD risk prediction beyond established risk factors.
MESA is an observational cohort of 6814 participants without clinical cardiovascular disease. All participants with diabetes and impaired fasting glucose were included in the analysis. The association between CAC, ABI, and incident ASCVD, and all-cause mortality was examined using Cox proportional hazard regression. The risk prediction models including ABI and/or CAC in addition to standard risk factors alone were compared.
Of the 1719 participants, 55% were male and average age was 64 (±9.6) years old. Participants with diabetes or impaired fasting glucose with higher CAC and lower ABI had higher ASCVD and all-cause mortality. ABI and CAC enhanced ASCVD discrimination over standard risk factors, with C-index (95% CI) of 0.689 (0.66, 0.718) for risk factors alone, 0.696 (0.668, 0.724) for ABI, 0.719 (0.691, 0.747) for CAC, and 0.721 (0.693, 0.749) for CAC + ABI. Similarly, for all-cause mortality, both CAC and ABI improved risk discrimination in addition to standard risk factors alone.
In a large population-based study of individuals with diabetes or impaired fasting glucose, the addition of ABI and CAC to conventional risk factors improved 10-year ASCVD risk prediction. ABI and CAC are non-invasive and cost-effective tests; therefore, these markers should be included into ASCVD risk stratification for primary prevention in the diabetic and impaired fasting glucose population.
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•ABI screening modestly improves ASCVD risk prediction in patients with diabetes.•Combination of ABI and CAC has an additive value for ASCVD risk prediction.•ABI and CAC are non-invasive and cost-effective subclinical atherosclerosis markers.
The objective of this study is to undertake a population based study on the incidence, prevalence, natural history, and response to treatment of complex regional pain syndrome (CRPS). All Mayo Clinic ...and Olmsted Medical Group medical records with codes for reflex sympathetic dystrophy (RSD), CRPS, and compatible diagnoses in the period 1989-1999 were reviewed as part of the Rochester Epidemiology Project. We used IASP criteria for CRPS. The study population was in the Olmsted County, Minnesota (1990 population, 106,470). The main outcome measures were CRPS I incidence, prevalence, and outcome. Seventy-four cases of CRPS I were identified, resulting in an incidence rate of 5.46 per 100,000 person years at risk, and a period prevalence of 20.57 per 100,000. Female:male ratio was 4:1, with a median age of 46 years at onset. Upper limb was affected twice as commonly as lower limb. All cases reported an antecedent event and fracture was the most common trigger (46%). Excellent concordance was found between symptoms and signs and vasomotor symptoms were the most commonly present. Three phase bone scan and autonomic testing diagnosed the condition in >80% of cases. Seventy-four percent of patients underwent resolution, often spontaneously. CRPS I is of low prevalence, more commonly affects women than men, the upper more than the lower extremity, and three out of four cases undergo resolution. These results suggest that invasive treatment of CRPS may not be warranted in the majority of cases.
Apolipoproteins (apo) C-I and C-II are key regulators of triglyceride and HDL metabolism. Both exist as full-size native and truncated (apoC-I'; apoC-II') posttranslational proteoforms. However, the ...determinants and the role of these proteoforms in lipid metabolism are unknown. Here, we measured apoC-I and apoC-II proteoforms by mass spectrometry immunoassay in baseline and 10-year follow-up plasma samples from the Multi-Ethnic Study of Atherosclerosis. We found that baseline total apoC-I (mean = 9.2 mg/dl) was lower in African American (AA), Chinese American (CA), and Hispanic American (by 1.8; 1.0; 1.0 mg/dl vs. whites), higher in women (by 1.2 mg/dl), and positively associated with plasma triglycerides and HDL. Furthermore, we observed that the truncated-to-native apoC-I ratio (apoC-I'/C-I) was lower in CA, negatively associated with triglycerides, and positively associated with HDL. We determined that total apoC-II (8.8 mg/dl) was lower in AA (by 0.8 mg/dl) and higher in CA and Hispanic American (by 0.5 and 0.4 mg/dl), positively associated with triglycerides, and negatively associated with HDL. In addition, apoC-II'/C-II was higher in AA and women, negatively associated with triglycerides, and positively associated with HDL. We showed that the change in triglycerides was positively associated with changes in total apoC-I and apoC-II and negatively associated with changes in apoC-I'/C-I and apoC-II'/C-II, whereas the change in HDL was positively associated with changes in total apoC-I and apoC-II'/C-II and negatively associated with change in total apoC-II. This study documents racial/ethnic variation in apoC-I and apoC-II plasma levels and highlights apolipoprotein posttranslational modification as a potential regulator of plasma lipids.
To determine if carotid plaque morphology and composition with magnetic resonance (MR) imaging can be used to identify asymptomatic subjects at risk for cardiovascular events.
Institutional review ...boards at each site approved the study, and all sites were Health Insurance Portability and Accountability Act (HIPAA) compliant. A total of 946 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated with MR imaging and ultrasonography (US). MR imaging was used to define carotid plaque composition and remodeling index (wall area divided by the sum of wall area and lumen area), while US was used to assess carotid wall thickness. Incident cardiovascular events, including myocardial infarction, resuscitated cardiac arrest, angina, stroke, and death, were ascertained for an average of 5.5 years. Multivariable Cox proportional hazards models, C statistics, and net reclassification improvement (NRI) for event prediction were determined.
Cardiovascular events occurred in 59 (6%) of participants. Carotid IMT as well as MR imaging remodeling index, lipid core, and calcium in the internal carotid artery were significant predictors of events in univariate analysis (P < .001 for all). For traditional risk factors, the C statistic for event prediction was 0.696. For MR imaging remodeling index and lipid core, the C statistic was 0.734 and the NRI was 7.4% and 15.8% for participants with and those without cardiovascular events, respectively (P = .02). The NRI for US IMT in addition to traditional risk factors was not significant.
The identification of vulnerable plaque characteristics with MR imaging aids in cardiovascular disease prediction and improves the reclassification of baseline cardiovascular risk.
IntroductionPrimary prevention of cardiovascular disease (CVD) emphasizes detection of subclinical atherosclerosis (SA). Diabetes Mellitus is a high-CVD risk condition with higher prevalence of ...systemic atherosclerosis. Ankle brachial index (ABI) and coronary artery calcium (CAC) are commonly used measures to detect SA. The primary objective of this study was to evaluate the improvement in CVD risk prediction beyond traditional risk factors after adding ABI and CAC within diabetic participants.MethodsMESA is an observational cohort of 6,814 participants free of clinical cardiovascular disease at baseline. Participants were included in this analysis if they had diabetes or impaired fasting glucose. Cox proportional hazard regression was used to assess the association between CAC score and ABI and outcomes (incident CVD and all-cause mortality). We compared the C-index between a model with traditional risk factors alone and models including ABI and/or CAC.Results1,719 participants were included in the analysis. Average age was 64 years, 55% male, 25% White, 13% Chinese, 34% Black, and 27% Hispanic. Higher CAC and lower ABI were associated with higher risk of CVD (Figure 1) and mortality among people with diabetes. Both ABI and CAC improved CVD discrimination over and above standard risk factors (C-index 0.689 for risk factors alone, 0.719 for CAC, 0.696 for ABI, and 0.721 for both). Similarly for mortality, discrimination was improved over risk factors alone (C-index 0.739) for CAC (0.746), ABI (0.747), and both (0.748).ConclusionThese two subclinical atherosclerosis measures may aid in clinical decision making among those with diabetes.
Our understanding of the specific aspects of vascular contributions to dementia remains unclear.
We aim to identify the correlates of incident dementia in a multi-ethnic cardiovascular cohort.
A ...total of 6806 participants with follow-up data for incident dementia were included. Probable dementia diagnoses were identified using hospitalization discharge diagnoses according to the International Classification of Diseases Codes (ICD). We used Random Forest analyses to identify the correlates of incident dementia and cognitive function from among 198 variables collected at the baseline MESA exam entailing demographic risk factors, medical history, anthropometry, lab biomarkers, electrocardiograms, cardiovascular magnetic resonance imaging, carotid ultrasonography, coronary artery calcium and liver fat content. Death and stroke were considered competing events.
Over 14 years of follow-up, 326 dementia events were identified. Beyond age, the top correlates of dementia included coronary artery calcification, high sensitivity troponin, common carotid artery intima to media thickness, NT-proBNP, physical activity, pulse pressure, tumor necrosis factor-α, history of cancer, and liver to spleen attenuation ratio from computed tomography. Correlates of cognitive function included income and physical activity, body size, serum glucose, glomerular filtration rate, measures of carotid artery stiffness, alcohol use, and inflammation indexed as IL-2 and TNF soluble receptors and plasmin-antiplasmin complex.
In a deeply phenotyped cardiovascular cohort we identified the key correlates of dementia beyond age as subclinical atherosclerosis and myocyte damage, vascular function, inflammation, physical activity, hepatic steatosis, and history of cancer.
The integrated discrimination improvement (IDI) index is a popular tool for evaluating the capacity of a marker to predict a binary outcome of interest. Recent reports have proposed that the IDI is ...more sensitive than other metrics for identifying useful predictive markers. In this article, the authors use simulated data sets and theoretical analysis to investigate the statistical properties of the IDI. The authors consider the common situation in which a risk model is fitted to a data set with and without the new, candidate predictor(s). Results demonstrate that the published method of estimating the standard error of an IDI estimate tends to underestimate the error. The z test proposed in the literature for IDI-based testing of a new biomarker is not valid, because the null distribution of the test statistic is not standard normal, even in large samples. If a test for the incremental value of a marker is desired, the authors recommend the test based on the model. For investigators who find the IDI to be a useful measure, bootstrap methods may offer a reasonable option for inference when evaluating new predictors, as long as the added predictive capacity is large.
Coronary artery calcium (CAC) has been demonstrated to be associated with the risk of coronary heart disease. The Multi-Ethnic Study of Atherosclerosis (MESA) provides a unique opportunity to examine ...the distribution of CAC on the basis of age, gender, and race/ethnicity in a cohort free of clinical cardiovascular disease and treated diabetes.
MESA is a prospective cohort study designed to investigate subclinical cardiovascular disease in a multiethnic cohort free of clinical cardiovascular disease. The percentiles of the CAC distribution were estimated with nonparametric techniques. Treated diabetics were excluded from analysis. There were 6110 included in the analysis, with 53% female and an average age of 62 years. Men had greater calcium levels than women, and calcium amount and prevalence were steadily higher with increasing age. There were significant differences in calcium by race, and these associations differed across age and gender. For women, whites had the highest percentiles and Hispanics generally had the lowest; in the oldest age group, however, Chinese women had the lowest values. Overall, Chinese and black women were intermediate, with their order dependent on age. For men, whites consistently had the highest percentiles, and Hispanics had the second highest. Blacks were lowest at the younger ages, and Chinese were lowest at the older ages. At the MESA public website (http://www.mesa-nhlbi.org), an interactive form allows one to enter an age, gender, race/ethnicity, and CAC score to obtain a corresponding estimated percentile.
The information provided here can be used to examine whether a patient has a high CAC score relative to others with the same age, gender, and race/ethnicity who do not have clinical cardiovascular disease or treated diabetes.
Lean muscle plays critical roles in physical functioning and metabolism. However, little is known regarding associations between muscle and mortality in adults.
The purpose was to evaluate ...associations between abdominal muscle quantity (area) and quality (density) with risk of all-cause mortality in a diverse cohort free of cardiovascular disease.
Data were taken from the Abdominal Body Composition, Inflammation, and Cardiovascular Disease ancillary study of the Multi-Ethnic Study of Atherosclerosis prospective cohort study. Participants were adults (45–85 years) free of extant cardiovascular disease, and of Hispanic, African American, Chinese, or Caucasian descent. Of the original 6814 MESA participants, a random, representative sample (n = 1974) participated in the ancillary body composition study. Abdominal muscle area and density were measured from computed tomography scans spanning L2-L4. Muscle density was measured as attenuation in Hounsfield units, and area was quantified as cm2. Gender-stratified cox proportional hazard models assessed the risk of all-cause mortality across gender-specific quartiles of muscle area and density adjusting for confounders, with area and density entered simultaneously.
At baseline, the mean age for men (n = 946) and women (n = 955) was 61.5 and 62.5 years and median follow-up time was 10.6 and 10.9 years, respectively. Muscle density was inversely associated with mortality, with the highest quartile of density showing a 73% reduction in risk for men (HR = 0.27, 95% CI = 0.14–0.51; p-trend<0.001) and 57% reduction for women (HR = 0.43, 95% CI = 0.18–1.01; p-trend = 0.04) compared to the lowest quartile when adjusting for mortality risk factors, lifestyle, BMI and visceral fat. There was no association between muscle area and all-cause mortality for men (p-trend = 0.58) or women (p-trend = 0.47).
Greater abdominal muscle density, but not muscle area, is associated with markedly lower risk of all-cause mortality across a decade of follow up. Muscle quality may be a powerful predictor of mortality in community dwelling adults.
•Abdominal muscle area and density were measured in adults via CT scan.•All-cause mortality was measured over 11 years of follow-up.•Baseline muscle density was robustly and inversely associated with mortality.•Muscle density was more protective for men than for women.•Baseline muscle area was not associated with mortality for men or women.
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