Racial and Ethnic Differences in All-Cause and Cardiovascular Disease Mortality: The MESA Study.

BACKGROUND: Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis). METHODS: MESA recruited 6814 US adults, 45 to 84 years of age, free of clinical CVD at baseline, including Black, White, Hispanic, and Chinese individuals (2000-2002). Using Cox proportional hazards modeling with time-updated covariates, we evaluated the association of self-reported race and ethnicity with all-cause and adjudicated CVD mortality, with progressive adjustments for age and sex, SES (neighborhood SES, income, education, and health insurance), lifestyle and psychosocial risk factors, clinical risk factors, and immigration history. RESULTS: During a median of 15.8 years of follow-up, 22.8% of participants (n=1552) died, of which 5.3% (n=364) died of CVD. After adjusting for age and sex, Black participants had a 34% higher mortality hazard (hazard ratio [HR], 1.34 [95% CI, 1.19-1.51]), Chinese participants had a 21% lower mortality hazard (HR, 0.79 [95% CI, 0.66-0.95]), and there was no mortality difference in Hispanic participants (HR, 0.99 [95% CI, 0.86-1.14]) compared with White participants. After adjusting for SES, the mortality HR for Black participants compared with White participants was reduced (HR, 1.16 [95% CI, 1.01-1.34]) but still statistically significant. With adjustment for SES, the mortality hazards for Chinese and Hispanic participants also decreased in comparison with White participants. After further adjustment for additional risk factors and immigration history, Hispanic participants (HR, 0.77 [95% CI, 0.63-0.94]) had a lower mortality risk than White participants, and hazard ratios for Black participants (HR, 1.08 [95% CI, 0.92-1.26]) and Chinese participants (HR, 0.81 [95% CI, 0.60-1.08]) were not significantly different from those of White participants. Similar trends were seen for CVD mortality, although the age- and sex-adjusted HR for CVD mortality for Black participants compared with White participants was greater than all-cause mortality (HR, 1.72 [95% CI, 1.34-2.21] compared with HR, 1.34 [95% CI, 1.19-1.51]). CONCLUSIONS: These results highlight persistent racial and ethnic differences in overall and CVD mortality, largely attributable to social determinants of health, and support the need to identify and act on systemic factors that shape differences in health across racial and ethnic groups.

Incidence of Interstitial Lung Abnormalities: The MESA Lung Study.

The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA have not been previously reported.Trained thoracic radiologists evaluated 13 944 cardiac CT scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis longitudinal cohort study participants >45 years of age from 2000 to 2012. 5% of the scans were re-read by the same or a different observer in a blinded fashion. After exclusion of participants with ILA at baseline, incidence rates and incidence rate ratios for ILA and fibrotic ILA were calculated.The intra-reader agreement of ILA was 92.0% (Gwet AC1=0.912, ICC=0.982) and the inter-reader agreement of ILA was 83.5% (Gwet AC1=0.814; ICC=0.969). Incidence of ILA and fibrotic ILA was estimated to be 13.1 cases/1000 person-years and 3.5/1000 person-years, respectively. In multivariable analyses, age (HR 1.06 (1.05, 1.08), p <0.001; HR 1.08 (1.06, 1.11), p <0.001), high attenuation area (HAA) at baseline (HR 1.05 (1.03, 1.07), p <0.001; HR 1.06 (1.02, 1.10), p=0.002), and the MUC5B promoter SNP (HR 1.73 (1.17, 2.56) p=0.01; HR 4.96 (2.68, 9.15), p <0.001) were associated with incident ILA and fibrotic ILA, respectively. Ever smoking (HR 2.31 (1.34, 3.96), p= 0.002) and an IPF polygenic risk score (HR 2.09 (1.61-2.71), p<0.001) were associated only with incident fibrotic ILA.Incident ILA and fibrotic ILA were estimated by review of cardiac imaging studies. These findings may lead to wider application of a screening tool for atherosclerosis to identify preclinical lung disease.

Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. METHODS: A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. RESULTS: In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR = 1.33, 95% CI = 1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. CONCLUSIONS: The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.

Exact inference for fixed effects meta-analysis of 2 × 2 $$ 2\times 2 $$ tables.

Meta-analysis of associations between rare outcomes and binary exposures are particularly important in studies of a drug's potential side-effects. But meta-analysis of the resulting 2 × 2 $$ 2\times 2 $$ contingency tables presents substantial practical difficulties, as analysts are currently forced to pick between "exact" inference-that eliminates concern over using large-sample approximations with small cell counts-and explicitly allowing for heterogeneity of the underlying effects. A controversial example is given by the Avandia meta-analysis (Nissen and Wolski. N Engl J Med. 2007;356(24):2457-2471) of rosiglitazone's effects on myocardial infarction and death. While the initial Avandia analysis-using simple methods-found a significant effect, its results conflict with subsequent re-analyses that use either exact methods, or that explicitly acknowledge the plausible heterogeneity. In this article, we aim to resolve these difficulties, by providing an exact (albeit conservative) method that is valid under heterogeneity. We also provide a measure of the degree of conservatism, that indicates the approximate extent of the excess coverage. Applied to the Avandia data, we find support for Nissen and Wolski 2007's original results. Given that our method does not require strong assumptions or large cell counts, and provides intervals around the well-known conditional maximum likelihood estimate, we anticipate that it could be an attractive default method for meta-analysis of 2 × 2 $$ 2\times 2 $$ tables featuring rare events.

Outcomes of Open Versus Percutaneous Access for Patients Enrolled in the GREAT Registry.

BACKGROUND: Arterial access and device delivery in endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR) have evolved from open femoral or iliac artery exposure to selective percutaneous arterial access. Although regional application of percutaneous access for these 2 procedures varies widely, the use of this technique continues to increase. Currently, differences in the use of percutaneous access between EVAR and TEVAR have not been well explored. The Gore Global Registry for Endovascular Aortic Treatment (GREAT) registry collected relevant data for evaluation of these issues and the comparative results between open and percutaneous approaches in regard to complication rates and length of stay (LOS). METHODS: This study was performed via a retrospective review of patients from the GREAT registry (Clinicaltrials.gov no. NCT01658787). The primary variable of this study was access site complications including postoperative hematoma, vessel dissection, and pseudoaneurysm. Patients were categorized by abdominal (EVAR) and thoracic (TEVAR) aortic procedures using percutaneous-only, cutdown-only, and combined vascular access techniques for a total of 6 groups. Standard statistical methodology was used to perform single-variable and multivariable analysis of a variety of covariates including LOS, geographical location of procedure, procedural success rate, and access sheath size. RESULTS: Of 4,781 patients from the GREAT registry, 3,837 (80.3%) underwent EVAR and 944 (19.7%) underwent TEVAR with percutaneous-only access techniques being used in 2,017 (42.2%) and cutdown-only in 2,446 (51.2%). There was variable application of percutaneous access by geographic region with Australia and New Zealand using this technique more frequently and Brazil using percutaneous access the least. No significant difference in the rate of access site complications was detected between the 6 groups of patients in the study; however, significantly lower rates of access site complications were associated with percutaneous-only compared with both cutdown-only and combined techniques (P = 0.03). In addition, associated with significantly higher rates of access site complications was longer LOS (P < 0.01). Average LOS was 5.2 days and was higher in the TEVAR group (10.1 days) than that in EVAR (4.0 days, P < 0.05). Increased sheath size does not appear to increase the risk of access site complication. CONCLUSIONS: There was no significant difference found in the complication rate between percutaneous and cutdown access techniques. This analysis demonstrates that percutaneous-only access is safe, has low complication rates, and has lower LOS compared with open access or combined access techniques.

Accuracy evaluations of three ruptured abdominal aortic aneurysm mortality risk scores using an independent dataset.

OBJECTIVE: To date, no single scoring system for predicting 30-day mortality in patients with ruptured abdominal aortic aneurysms (rAAAs) has been endorsed by any vascular society or proven to definitively predict treatment futility. Three recently developed scoring systems for predicting 30-day mortality in patients with rAAA have been validated by their respective institutional data. The purpose of this study was to evaluate the accuracy of these rAAA mortality risk scores using an independent community hospital dataset. METHODS: Consecutive patients presenting with rAAA at Saint Joseph Hospital between January 1, 2009, and February 28, 2017, were used for validation. Logistic regression analysis was used to evaluate the association between risk score and odds of death. Confidence intervals were calculated using the Wilson method. Comparisons were made between models by calculating the area under the receiver operating characteristic (AUC) curves. RESULTS: Complete data from 38 patients was used for accuracy evaluation. The AUCs for the Dutch Aneurysm Score, Harborview Medical Center score, and Vascular Surgery Group of New England (VSGNE) score were 0.762, 0.792, and 0.860, respectively, for all patients. When evaluating 30-day mortality for patients undergoing ruptured endovascular aneurysm repair, the scores were 0.802, 0.893, and 0.927, respectively. The difference between scores did not reach statistical significance. All three indexes significantly associated with the mortality rate using logistic regression. CONCLUSIONS: Each risk score accurately predicted 30-day mortality using the independent dataset. The results suggest that the VSGNE score is the most accurate; however, differences in accuracy between each scoring system did not reach statistical significance. The Harborview Medical Center scoring system is based only on preoperative variables. Although the VSGNE score had the highest AUC in this analysis, it is dependent on intraoperative variables. The authors favor a single risk assessment tool, with consensus vascular societal approval, that incorporates preoperative variables and includes a tool for the prediction of treatment futility.

CPR Blitzkrieg: Training 500 High School Students in less than 48 hours.

BACKGROUND Many states, including Arkansas, require CPR training before high school graduation. METHODS We modified the American Heart Association's CPR in Schools curriculum to deliver CPR and AED training with maximal individual practice. RESULTS 520 students were trained over a two-day period at Little Rock Central High School. Three students were unable to effectively participate due to physical limitations. The model was later applied at the five other district public high schools. CONCLUSIONS Training large numbers of students in a time-compressed formal is feasible with a highly dedicated, practiced instructor team. This model may be applicable to workplace settings.

Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Apolipoprotein C-III (apoC-III) proteoform composition shows distinct relationships with plasma lipids and cardiovascular risk. The present study tested whether apoC-III proteoforms are associated with risk of peripheral artery disease (PAD). METHODS: ApoC-III proteoforms, i.e., native (C-III0a), and glycosylated with zero (C-III0b), one (C-III1) or two (C-III2) sialic acids, were measured by mass spectrometry immunoassay on 5,734 Multi-Ethnic Study of Atherosclerosis participants who were subsequently followed for clinical PAD over 17 years. Ankle-brachial index (ABI) was also assessed at baseline and then 3 and 10 years later in 4,830 participants. RESULTS: Higher baseline C-III0b/C-III1 and lower baseline C-III2/C-III1 were associated with slower decline in ABI (follow-up adjusted for baseline) over time, independently of cardiometabolic risk factors, and plasma triglycerides and HDL cholesterol levels (estimated difference per 1 SD was 0.31 % for both, p < 0.01). The associations between C-III2/C-III1 and changes in ABI were stronger in men (-1.21 % vs. -0.27 % in women), and in Black and Chinese participants (-0.83 % and -0.86 % vs. 0.12 % in White). Higher C-III0b/C-III1 was associated with a trend for lower risk of PAD (HR = 0.84 [95%CI: 0.67-1.04]) that became stronger after excluding participants on lipid-lowering medications (0.73 [95%CI: 0.57-0.94]). Neither change in ABI nor clinical PAD was related to total apoC-III levels. CONCLUSIONS: We found associations of apoC-III proteoform composition with changes in ABI that were independent of other risk factors, including plasma lipids. Our data further support unique properties of apoC-III proteoforms in modulating vascular health that go beyond total apoC-III levels.

Peroral Endoscopic Myotomy May Be Safe in Solid-Organ Transplant Patients With Achalasia.

Peroral endoscopy myotomy (POEM) is a safe and effective therapy for achalasia among the general population. However, data regarding its safety and efficacy in organ transplant recipients are lacking. These patients present unique risks and challenges because of chronic immunosuppression. We present 3 cases of successful POEM performed safely for achalasia in patients with previous solid-organ transplantation without interruption of their immunosuppression medications. This case series suggests that POEM may be safe in solid-organ transplant recipients.

Exact inference for fixed-effects meta-analysis of proportions.

Meta-analysis of proportions is conceptually simple: Faced with a binary outcome in multiple studies, we seek inference on some overall proportion of successes/failures. Under common effect models, exact inference has long been available, but is not when we more realistically allow for heterogeneity of the proportions. Instead a wide range of nonexact fixed-effects methods are used, the interpretation of some of which is challenging. In this paper, we present methods for exact statistical tests and confidence intervals for fixed-effects meta-analysis of proportions. These methods retain the interpretability of the underlying parameter of interest, and can be implemented in straightforward software. We also show how our inference on the overall proportion is compatible with exact inference on heterogeneity of proportions. An illustrative example from a recent kidney disease study shows how the method's performance can be assessed in practice.

Relation of Progression of Coronary Artery Calcium to Dementia (from the Multi-Ethnic Study of Atherosclerosis).

Baseline coronary artery calcification has been shown to be associated with dementia. However, the value of coronary artery calcium (CAC) progression in the prediction of dementia remains unclear. In this study, we examined the association between CAC progression and dementia in the Multi-Ethnic Study of Atherosclerosis. The Multi-Ethnic Study of Atherosclerosis is a prospective study consisting of 6,814 participants 45 to 84 years of age, free of overt cardiovascular disease at baseline. A total of 5,570 subjects had baseline and follow-up CAC scans approximately 2.5 years apart and were included this analysis. A total of 4,173 of these participants completed cognitive testing with the Cognitive Abilities Screening Instrument (CASI) approximately 10 years after the baseline CAC scan. Dementia diagnoses were identified using International Classification of Diseases codes from hospitalizations, death certificates, and medications used to treat dementia. The absolute change between baseline and follow-up CAC was used to assess CAC progression. Cox proportional hazards and multivariable linear regression models were used to examine the association of CAC progression with incident dementia and with CASI score. Over a median follow-up of 13.2 (interquartile range: 11.2 to 15.3) years, 350 participants developed incident dementia. CAC progression showed no association with dementia risk after adjustment for age, gender, race/ethnicity, vascular risk factors, and baseline CAC score. There was no association of CAC progression with CASI score in any adjusted model. In conclusion, progression of CAC over approximately 2.5 years was not associated with increased risk of dementia after adjustment for demographic variables, vascular risk factors, and baseline CAC.

Stable formation of compositionally unique stress granules in virus-infected cells.

Stress granules are sites of mRNA storage formed in response to a variety of stresses, including viral infections. Here, the mechanisms and consequences of stress granule formation during poliovirus infection were examined. The results indicate that stress granules containing T-cell-restricted intracellular antigen 1 (TIA-1) and mRNA are stably constituted in infected cells despite lacking intact RasGAP SH3-domain binding protein 1 (G3BP) and eukaryotic initiation factor 4G. Fluorescent in situ hybridization revealed that stress granules in infected cells do not contain significant amounts of viral positive-strand RNA. Infection does not prevent stress granule formation in response to heat shock, indicating that poliovirus does not block de novo stress granule formation. A mutant TIA-1 protein that prevents stress granule formation during oxidative stress also prevents formation in infected cells. However, stress granule formation during infection is more dependent upon ongoing transcription than is formation during oxidative stress or heat shock. Furthermore, Sam68 is recruited to stress granules in infected cells but not to stress granules formed in response to oxidative stress or heat shock. These results demonstrate that stress granule formation in poliovirus-infected cells utilizes a transcription-dependent pathway that results in the appearance of stable, compositionally unique stress granules.

Intravascular lithotripsy during transcarotid arterial revascularization for highly calcified lesions in high-risk patients.

Transcarotid arterial revascularization (TCAR) with flow reversal offers a less invasive option for carotid revascularization in high-risk surgical patients. TCAR has been shown to have similar complication rates for stroke and mortality compared with carotid endarterectomy and lower complication rates compared with transfemoral carotid artery stenting. A relative contraindication for carotid stenting includes heavily calcified lesions. Intravascular lithotripsy has been approved for use in other vascular beds for endovascular treatment of heavily calcified lesions. In the present report, we have demonstrated the application of intravascular lithotripsy for heavily calcified carotid lesions, enabling treatment with TCAR for those who otherwise might be at high risk of transfemoral carotid artery stenting or carotid endarterectomy.

Direct access of ascending aorta for endograft delivery in the descending thoracic aorta.

First-line therapy for aneurysm, dissection, or rupture of the descending thoracic aorta is now by the endovascular approach. Retrograde insertion of the endograft, through access from the femoral arteries, is the preferred approach. This case presents a new, innovative technique for delivery of an endoprosthesis into the descending thoracic aorta when hostile anatomy prevents delivery from the femoral arteries, iliac arteries, or infrarenal abdominal aorta in a patient not suitable for open repair.

Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications.

BACKGROUND AND OBJECTIVES: Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman-Tukey double-arcsine transformations were used to stabilize variance as complications were rare. RESULTS: A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location. CONCLUSIONS: Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.

Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.

Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and monocyte-derived DCs (MDDCs). A CPXV infection of DCs at a multiplicity of infection of 10 was nonproductive, altered cellular morphology, and failed to reduce cell viability. A CPXV infection of DCs did not stimulate cytokine or chemokine secretion directly, but suppressed toll-like receptor (TLR) agonist-induced cytokine secretion and a DC-stimulated mixed leukocyte reaction (MLR). LPS-stimulated NF-κB nuclear translocation and host cytokine gene transcription were suppressed in CPXV-infected MDDCs. Early viral immunomodulatory genes were upregulated in MDDCs, consistent with early DC immunosuppression via synthesis of intracellular viral proteins. We conclude that a nonproductive CPXV infection suppressed DC immune function by synthesizing early intracellular viral proteins that suppressed DC signaling pathways.