Noninvasive respiratory support for acute respiratory failure due to COVID-19.

PURPOSE OF REVIEW: Noninvasive respiratory support has been widely applied during the COVID-19 pandemic. We provide a narrative review on the benefits and possible harms of noninvasive respiratory support for COVID-19 respiratory failure. RECENT FINDINGS: Maintenance of spontaneous breathing by means of noninvasive respiratory support in hypoxemic patients with vigorous spontaneous effort carries the risk of patient self-induced lung injury: the benefit of averting intubation in successful patients should be balanced with the harms of a worse outcome in patients who are intubated after failing a trial of noninvasive support.The risk of noninvasive treatment failure is greater in patients with the most severe oxygenation impairment (PaO2/FiO2 < 200 mmHg).High-flow nasal oxygen (HFNO) is the most widely applied intervention in COVID-19 patients with hypoxemic respiratory failure. Also, noninvasive ventilation (NIV) and continuous positive airway pressure delivered with different interfaces have been used with variable success rates. A single randomized trial showed lower need for intubation in patients receiving helmet NIV with specific settings, compared to HFNO alone.Prone positioning is recommended for moderate-to-severe acute respiratory distress syndrome patients on invasive ventilation. Awake prone position has been frequently applied in COVID-19 patients: one randomized trial showed improved oxygenation and lower intubation rate in patients receiving 6-h sessions of awake prone positioning, as compared to conventional management. SUMMARY: Noninvasive respiratory support and awake prone position are tools possibly capable of averting endotracheal intubation in COVID-19 patients; carefully monitoring during any treatment is warranted to avoid delays in endotracheal intubation, especially in patients with PaO2/FiO2 < 200 mmHg.

Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial.

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. Design, Setting, and Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). Main Outcomes and Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99). Conclusions and Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.

Necessity of hospitalization and stress testing in low risk chest pain patients.

BACKGROUND: Copeptin is a marker of endogenous stress including early myocardial infarction(MI) and has value in early rule out of MI when used with cardiac troponin I(cTnI). OBJECTIVES: The goal of this study was to demonstrate that patients with a normal electrocardiogram and cTnI<0.040µg/l and copeptin<14pmol/l at presentation and after 2 h may be candidates for early discharge with outpatient follow-up potentially including stress testing. METHODS: This study uses data from the CHOPIN trial which enrolled 2071 patients with acute chest pain. Of those, 475 patients with normal electrocardiogram and normal cTnI(<0.040µg/l) and copeptin<14pmol/l at presentation and after 2 h were considered "low risk" and selected for further analysis. RESULTS: None of the 475 "low risk" patients were diagnosed with MI during the 180day follow-up period (including presentation). The negative predictive value of this strategy was 100% (95% confidence interval(CI):99.2%-100.0%). Furthermore no one died during follow up. 287 (60.4%) patients in the low risk group were hospitalized. In the "low risk" group, the only difference in outcomes (MI, death, revascularization, cardiac rehospitalization) was those hospitalized underwent revascularization more often (6.3%[95%CI:3.8%-9.7%] versus 0.5%[95%CI:0.0%-2.9%], p=.002). The hospitalized patients were tested significantly more via stress testing or angiogram (68.6%[95%CI:62.9%-74.0%] vs 22.9%[95%CI:17.1%-29.6%], p<.001). Those tested had less cardiac rehospitalizations during follow-up (1.7% vs 5.1%, p=.040). CONCLUSIONS: In conclusion, patients with a normal electrocardiogram, troponin and copeptin at presentation and after 2 h are at low risk for MI and death over 180days. These low risk patients may be candidates for early outpatient testing and cardiology follow-up thereby reducing hospitalization.

Clinical Impact of Heparin Kinetics During Catheter Ablation of Atrial Fibrillation: Meta-Analysis and Meta-Regression.

INTRODUCTION: Appropriate activated clotting time (ACT) during catheter ablation of atrial fibrillation (CA-AF) is essential to minimize periprocedural complications. METHODS AND RESULTS: An electronic search was performed using major databases. Outcomes were thromboembolic (TE) and bleeding complications according to ACT levels (seconds). Heparin dose (U/kg) and time (minutes) to achieve the target ACT was compared among patients receiving vitamin K antagonist (VKA) versus non-VKA oral anticoagulants (NOAC). Nineteen studies involving 7,150 patients were identified. Patients with ACT > 300 had less TE (OR, 0.51; 95% CI 0.35-0.74) and bleeding (OR, 0.70; 95% CI 0.60-0.83) compared to ACT < 300, when using any type of oral anticoagulation. The use of VKA was associated with reduced heparin requirements (mean dose: 157 U/kg vs. 209 U/kg, P < 0.03; SDM -0.86 [95% CI -1.39 to -0.33]), and with lower time to achieve the target ACT (mean time: 24 minutes vs. 49 minutes, P < 0.03; SDM -11.02 [95% CI -13.29 to -8.75]) compared to NOACs. No significant publication bias was found. CONCLUSIONS: Performing CA-AF with a target ACT > 300 decreases the risk of TE without increasing the risk of bleeding. Patients receiving VKAs required less heparin and reached the target ACT faster compared to NOACs.

Trans-ethnic meta-analysis identifies common and rare variants associated with hepatocyte growth factor levels in the Multi-Ethnic Study of Atherosclerosis (MESA).

Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor that regulates cell growth, motility, mitogenesis, and morphogenesis in a variety of cells, and increased serum levels of HGF have been linked to a number of clinical and subclinical cardiovascular disease phenotypes. However, little is currently known regarding which genetic factors influence HGF levels, despite evidence of substantial genetic contributions to HGF variation. Based upon ethnicity-stratified single-variant association analysis and trans-ethnic meta-analysis of 6201 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we discovered five statistically significant common and low-frequency variants: HGF missense polymorphism rs5745687 (p.E299K) as well as four variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC. We also identified two significant ethnicity-specific gene-level associations (A1BG in African Americans; FASN in Chinese Americans) based upon low-frequency/rare variants, while meta-analysis of gene-level results identified a significant association for HGFAC. However, identified single-variant associations explained modest proportions of the total trait variation and were not significantly associated with coronary artery calcium or coronary heart disease. Our findings indicate that genetic factors influencing circulating HGF levels may be complex and ethnically diverse.

Multi-ethnic analysis reveals soluble L-selectin may be post-transcriptionally regulated by 3'UTR polymorphism: the Multi-Ethnic Study of Atherosclerosis (MESA).

L-Selectin is constitutively expressed on leukocytes and mediates their interaction with endothelial cells during inflammation. Previous studies on the association of soluble L-selectin (sL-selectin) with cardiovascular disease (CVD) are inconsistent. Genetic variants associated with sL-selectin levels may be a better surrogate of levels over a lifetime. We explored the association of genetic variants and sL-selectin levels in a race/ethnicity stratified random sample of 2,403 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Through a genome-wide analysis with additive linear regression models, we found that rs12938 on the SELL gene accounted for a significant portion of the protein level variance across all four races/ethnicities. To evaluate potential additional associations, elastic net models were used for variants located in the SELL/SELP/SELE genetic region and an additional two SNPs, rs3917768 and rs4987361, were associated with sL-selectin levels in African Americans. These variants accounted for a portion of protein variance that ranged from 4 % in Hispanic to 14 % in African Americans. To investigate the relationship of these variants with CVD, 6,317 subjects were used. No significant association was found between any of the identified SNPs and carotid intima-media thickness or presence of carotid plaque using linear and logistic regression, respectively. Similarly no significant results were found for coronary artery calcium or coronary heart disease events. In conclusion, we found that variants within the SELL gene are associated with sL-selectin levels. Despite accounting for a significant portion of the protein level variance, none of the variants was associated with clinical or subclinical CVD.

Contemporary trends in heart failure with reduced and preserved ejection fraction after myocardial infarction: a community study.

Major changes have recently occurred in the epidemiology of myocardial infarction (MI) that could possibly affect outcomes such as heart failure (HF). Data describing trends in HF after MI are scarce and conflicting and do not distinguish between preserved and reduced ejection fraction (EF). We evaluated temporal trends in HF after MI. All residents of Olmsted County, Minnesota (n = 2,596) who had a first-ever MI diagnosed in 1990-2010 and no prior HF were followed-up through 2012. Framingham Heart Study criteria were used to define HF, which was further classified according to EF. Both early-onset (0-7 days after MI) and late-onset (8 days to 5 years after MI) HF were examined. Changes in patient presentation were noted, including fewer ST-segment-elevation MIs, lower Killip class, and more comorbid conditions. Over the 5-year follow-up period, 715 patients developed HF, 475 of whom developed it during the first week. The age- and sex-adjusted risk declined from 1990-1996 to 2004-2010, with hazard ratios of 0.67 (95% confidence interval (CI): 0.54, 0.85) for early-onset HF and 0.63 (95% CI: 0.45, 0.86) for late-onset HF. Further adjustment for patient and MI characteristics yielded hazard ratios of 0.86 (95% CI: 0.66, 1.11) and 0.63 (95% CI: 0.45, 0.88) for early- and late-onset HF, respectively. Declines in early-onset and late-onset HF were observed for HF with reduced EF (<50%) but not for HF with preserved EF, indicating a change in the case mix of HF after MI that requires new prevention strategies.

Heart failure performance measures: eligibility and implementation in the community.

BACKGROUND: The goal of heart failure (HF) performance measures is to improve quality of care by assessing the implementation of guidelines in eligible patients. Little is known about the proportion of eligible patients and how performance measures are implemented in the community. METHODS: We determined the eligibility for and adherence to performance measures and ß-blocker therapy in a community-based cohort of hospitalized HF patients from January 2005 to June 2011. RESULTS: All of the 465 HF inpatients (median age 76 years, 48% men) included in the study received an ejection fraction assessment. Only 164 had an ejection fraction <40% thus were candidates for ß-blocker and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB) therapy. Considering absolute contraindications, 99 patients were eligible to receive ACE inhibitors/ARB, and 162 to receive ß-blockers. Among these, 85% received ACE inhibitors/ARBs and 91% received ß-blockers. Among the 261 individuals with atrial fibrillation, 89 were eligible for warfarin and 54% received it. Of 52 current smokers, 69% received cessation counseling during hospitalization. CONCLUSION: In the community, among eligible hospitalized HF patients, the implementation of performance measures can be improved. However, as most patients are not candidates for current performance measures, other approaches are needed to improve care and outcomes.

Clinical features and 28-day mortality predictors of vaccinated patients admitted to a COVID-19 ICU hub in Italy.

BACKGROUND: COVID-19 vaccination has been proved to be effective in preventing hospitalization and illness progression, even though data on mortality of vaccinated patients in the intensive care unit (ICU) are conflicting. The aim of this study was to investigate the characteristics of vaccinated patients admitted to ICU according to their immunization cycle and to outline the risk factors for 28-day mortality. This observational study included adult patients admitted to ICU for acute respiratory failure (ARF) due to SARS-CoV-2 and who had received at least one dose of vaccine. RESULTS: Fully vaccination was defined as a complete primary cycle from < 120 days or a booster dose from > 14 days. All the other patients were named partially vaccinated. One-hundred sixty patients (91 fully and 69 partially vaccinated) resulted eligible, showing a 28-day mortality rate of 51.9%. Compared to partially vaccinated, fully vaccinated were younger (69 [60-77.5] vs. 74 [66-79] years, p 0.029), more frequently immunocompromised (39.56% vs. 14.39%, p 0.003), and affected by at least one comorbidity (90.11% vs 78.26%, p 0.045), mainly chronic kidney disease (CKD) (36.26% vs 20.29%, p 0.035). At multivariable analysis, independent predictors of 28-day mortality were as follows: older age [OR 1.05 (CI 95% 1.01-1.08), p 0.005], history of chronic obstructive pulmonary disease (COPD) [OR 3.05 (CI 95% 1.28-7.30), p 0.012], immunosuppression [OR 3.70 (CI 95% 1.63-8.40), p 0.002], and admission respiratory and hemodynamic status [PaO2/FiO2 and septic shock: OR 0.99 (CI 95% 0.98-0.99), p 0.009 and 2.74 (CI 95% 1.16-6.48), p 0.022, respectively]. CONCLUSIONS: Despite a full vaccination cycle, severe COVID-19 may occur in patients with relevant comorbidities, especially immunosuppression and CKD. Regardless the immunization status, predisposing conditions (i.e., older age, COPD, and immunosuppression) and a severe clinical presentation were predictors of 28-day mortality.

Implications of cancer prior to and after heart transplantation.

Cancer and cardiovascular disease share many risk factors. Due to improved survival of patients with cancer, the cohort of cancer survivors with heart failure referred for heart transplantation (HT) is growing. Specific considerations include time interval between cancer treatment and HT, risk for recurrence and risk for de novo malignancy (dnM). dnM is an important cause of post-HT morbidity and mortality, with nearly a third diagnosed with malignancy by 10 years post-HT. Compared with the age-matched general population, HT recipients have an approximately 2.5-fold to 4-fold increased risk of developing cancer. HT recipients with prior malignancy show variable cancer recurrence rates, depending on years in remission before HT: 5% recurrence if >5 years in remission, 26% recurrence if 1-5 years in remission and 63% recurrence if <1 year in remission. A myriad of mechanisms influence oncogenesis following HT, including reduced host immunosurveillance from chronic immunosuppression, influence of oncogenic viruses, and the cumulative intensity and duration of immunosuppression. Conversely, protective factors include acyclovir prophylaxis, use of proliferation signal inhibitors (PSI) and female gender. Management involves reducing immunosuppression, incorporating a PSI for immunosuppression and heightened surveillance for allograft rejection. Cancer treatment, including immunotherapy, may be cardiotoxic and lead to graft failure or rejection. Additionally, there exists a competing risk to reduce immunosuppression to improve cancer outcomes, which may increase risk for rejection. A multidisciplinary cardio-oncology team approach is recommended to optimise care and should include an oncologist, transplant cardiologist, transplant pharmacist, palliative care, transplant coordinator and cardio-oncologist.

The History of Durable Left Ventricular Assist Devices and Comparison of Outcomes: HeartWare, HeartMate II, HeartMate 3, and the Future of Mechanical Circulatory Support.

The utilization of left ventricular assist devices (LVADs) in end-stage heart failure has doubled in the past ten years and is bound to continue to increase. Since the first of these devices was approved in 1994, the technology has changed tremendously, and so has the medical and surgical management of these patients. In this review, we discuss the history of LVADs, evaluating survival and complications over time. We also aim to discuss practical aspects of the medical and surgical management of LVAD patients and future directions for outcome improvement in this population.

Association of soluble Flt-1 with heart failure and cardiac morphology: The MESA angiogenesis study.

BACKGROUND: Soluble Fms-like tyrosine kinase 1 (sFlt-1) may inhibit angiogenesis. Higher levels of sFlt-1 are associated with worse prognosis in prevalent heart failure patients. The aim of this study was to better understand the role of sFlt-1 in heart failure pathogenesis by characterizing relationships between sFlt-1, cardiac morphology, and the composite outcome of incident heart failure or cardiovascular (CV) death in in a multiethnic cohort free of CV disease at baseline. METHODS: sFlt-1 was measured in 1,381 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis sub-study. Linear regression was used to estimate the association between sFlt-1 and cardiac morphology and Cox proportional hazard regression was used to estimate associations with incident heart failure or CV mortality. RESULTS: Over a median follow-up of 13.1 years, higher sFlt-1 levels were associated with incident heart failure or CV mortality independent from CV risk factors or NT-proBNP levels (HR 1.17, 95% CI 1.10-1.26, p < 0.001). Higher sFlt-1 levels were also associated with greater baseline left ventricular (LV) mass by cardiac MRI and increased loss of LV mass over the 10 years following the baseline exam (p-value 0.02 for each), but this association was no longer statistically significant after adjustment for baseline NT-proBNP (p = 0.11 and 0.10 respectively). CONCLUSIONS: Baseline sFlt-1 levels are associated with incident heart failure and cardiovascular mortality independent of traditional CV risk factors or NT-proBNP. An association was also found with cardiac mass but was no longer significant after adjustment for NT-proBNP.

Dyspnoea and clinical outcome in critically ill patients receiving noninvasive support for COVID-19 respiratory failure: post hoc analysis of a randomised clinical trial.

In #COVID19 patients, presence of moderate-to-severe dyspnoea is a marker of disease severity correlated to clinical outcomes https://bit.ly/3Bp2G1b.

Association of human immunodeficiency virus and hepatitis C virus infection with long-term outcomes post-ST segment elevation myocardial infarction in a disadvantaged urban community.

BACKGROUND: HIV and HCV have been linked to an increased risk of cardiovascular disease (CVD). Their impact on long-term outcomes following ST-segment myocardial infarction (STEMI) has not been previously studied. METHODS: We leveraged data from a STEMI registry (n = 1208) at an inner-city health system to assess the influence of HIV and HCV on post-STEMI outcomes. Cox regression was used to compare HIV-monoinfected (n = 22), HCV-monoinfected (n = 26) and HIV-HCV-coinfected patients (n = 8) with the neither-infected group (n = 1152) with regard to death, death or any readmission, and death or CVD readmission. RESULTS: The cohort was majority black or Hispanic. Median follow-up was 4.3 years. Compared to the neither-infected group, the HIV-monoinfected group showed near-significantly higher risks of death or any readmission (HR = 1.62, 95% CI = 0.96, 2.74) and death or CVD readmission (HR = 1.82, 95% CI = 0.98, 3.39) after full adjustment. On similar comparison, the HCV-monoinfected group exhibited significantly higher risks of death (HR = 2.09, 95% CI = 1.05, 4.15) and death or any readmission (HR = 1.68, 95% CI = 1.07, 2.65), whereas the HIV-HCV-coinfected group showed higher risk of death (HR = 6.51, 95% CI = 2.28, 18.61). CONCLUSIONS: In this cohort composed mostly of race-ethnic minorities, HIV monoinfection tended to be associated with 1.6-to-1.8-fold higher risk of death or readmission for any cause or CVD over long-term follow-up compared to neither infection, whereas HCV monoinfection was associated with 1.7-to-2.1-fold higher risk of death and death or any readmission, and HIV-HCV coinfection with 6.5-fold higher risk of death. These associations require further study in larger populations, but highlight the importance of identifying and treating HIV and HCV in patients presenting with STEMI.

Angiotensin-Neprilysin Inhibition in Black Americans: Data From the PIONEER-HF Trial.

OBJECTIVES: This study compared the efficacy and safety of sacubitril/valsartan to enalapril in Black and non-Black Americans with acute decompensated heart failure (ADHF). BACKGROUND: Black patients have a different response to treatment with angiotensin-converting enzyme inhibitors compared with other racial and ethnic groups. How Black patients with ADHF respond to sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is unclear. PIONEER-HF was a double-blind randomized clinical trial of sacubitril/valsartan versus enalapril in hospitalized patients with ADHF following hemodynamic stabilization. METHODS: In a pre-specified subgroup analysis, we examined changes in N-terminal pro-B-type natriuretic peptide, clinical outcomes, and safety according to race. RESULTS: The study population, all enrolled in the United States, included 316 (36%) Black participants, 515 (58%) White participants, and 50 (5.7%) participants of other racial groups. The reduction in N-terminal pro-B-type natriuretic peptide concentration at weeks 4 and 8 was significantly greater with sacubitril/valsartan than enalapril in both Black (ratio of change with sacubitril/valsartan vs. enalapril: 0.71; 95% confidence interval [CI]: 0.58 to 0.88) and non-Black patients (ratio of change: 0.71; 95% CI: 0.61 to 0.83; interaction p = 1.00). Compared with enalapril, sacubitril/valsartan also reduced the pre-specified exploratory composite of cardiovascular death or HF rehospitalization in both Black (hazard ratio: 0.47; 95% CI: 0.24 to 0.93) and non-Black patients (hazard ratio: 0.65; 95% CI: 0.40 to 1.06; interaction p = 0.44). CONCLUSIONS: Among Black patients admitted with ADHF in the United States, the in-hospital initiation of sacubitril/valsartan was more effective than enalapril in reducing natriuretic peptide levels and the composite of cardiovascular death or HF rehospitalization. The effect of sacubitril/valsartan did not differ by race. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).

Relation of Body Mass Index to Development of Atrial Fibrillation in Hispanics, Blacks, and Non-Hispanic Whites.

No previous studies have examined the interaction between body mass index (BMI) and race/ethnicity with the risk of atrial fibrillation (AF). We retrospectively followed 48,323 persons free of AF (43% Hispanic, 37% black, and 20% white; median age 60 years) for subsequent incident AF (ascertained from electrocardiograms). BMI categories included very severely underweight (BMI <15 kg/m2), severely underweight (BMI 15.1 to 15.9 kg/m2), underweight (BMI 16 to 18.4 kg/m2), normal (BMI 18.5 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), moderately obese (BMI 30 to 34.9 kg/m2), severely obese (BMI 35 to 39.9 kg/m2), and very severely obese (BMI >40 kg/m2). Cox regression analysis controlled for baseline covariates: heart failure, gender, age, treatment for hypertension, diabetes, PR length, systolic blood pressure, left ventricular hypertrophy, socioeconomic status, use of ß blockers, calcium channel blockers, and digoxin. Over a follow-up of 13 years, 4,744 AF cases occurred. BMI in units of 10 was associated with the development of AF (adjusted hazard ratio 1.088, 95% confidence interval 1.048 to 1.130, p <0.01). When stratified by race/ethnicity, non-Hispanic whites compared with blacks and Hispanics had a higher risk of developing AF, noted in those whom BMI classes were overweight to severely obese. In conclusion, our study demonstrates that there exists a relation between obesity and race/ethnicity for the development of AF. Non-Hispanic whites had a higher risk of developing AF compared with blacks and Hispanics.

ABO blood group is associated with peripheral arterial disease in African Americans: The Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Peripheral artery disease (PAD) affects 8.5 million Americans and thus improving our understanding of PAD is critical to developing strategies to reduce disease burden. The objective of the study was to determine the association of ABO blood type with ankle brachial index (ABI) as well as prevalent and incident PAD in a multi-ethnic cohort. METHODS: The Multi-Ethnic Study of Atherosclerosis includes non-Hispanic White, African, Hispanic, and Chinese Americans aged 45-84. ABO blood type was estimated using ABO genotypes in 6027 participants who had ABI assessed at the baseline exam. Associations with ABO blood type were evaluated categorically and under an additive genetic model by number of major ABO alleles. After excluding those with ABI>1.4, prevalent PAD was defined as ABI≤0.9 at baseline and incident PAD as ABI≤0.9 for 5137 participants eligible for analysis. RESULTS: There were 222 prevalent cases and 239 incident cases of PAD. In African Americans, each additional copy of the A allele was associated with a 0.02 lower baseline ABI (p=0.006). Each copy of the A allele also corresponded to 1.57-fold greater odds of prevalent PAD (95% CI, 1.17-2.35; p=0.004), but was not associated with incident PAD. No associations were found in other racial/ethnic groups for ABI, prevalent PAD, or incident PAD across all races/ethnicities. CONCLUSIONS: Blood type A and the A allele count were significantly associated with baseline ABI and prevalent PAD in African Americans. Further research is needed to confirm and study the mechanisms of this association in African Americans.

Low high-density lipoprotein cholesterol and particle concentrations are associated with greater levels of endothelial activation markers in Multi-Ethnic Study of Atherosclerosis participants.

BACKGROUND: High-density lipoproteins (HDL) are well characterized for their role in reverse cholesterol transport but may confer other cardiovascular benefits-specifically, HDL may suppress the endothelial activation cascade in the initiating stages of atherogenesis. OBJECTIVE: It was the primary aim of this study to examine the relations of HDL cholesterol (HDL-C), total HDL particle (HDL-P) concentrations, and HDL-P subclasses with circulating levels of endothelial activation markers in a subcohort of Multi-Ethnic Study of Atherosclerosis participants. METHODS: HDL-C was measured by enzymatic assay, and total HDL-P and subclass concentrations were assessed by nuclear magnetic resonance spectroscopy. Concentrations of circulating endothelial activation markers were determined through immunoassay. Multivariable linear regression was used to determine the cross-sectional associations between HDL variables and endothelial markers with statistical adjustment for age, race/ethnicity, sex, education, systolic blood pressure, hypertension medication use, body mass index, smoking status, lipid-lowering medication use, serum creatinine, diabetes, low-density lipoprotein cholesterol, and coronary artery calcium. RESULTS: HDL-C and HDL-P were found to be inversely associated with soluble vascular cell adhesion molecule-1, soluble vascular intracellular adhesion molecule-1, sL-selectin, and sP-selectin; HDL-P was additionally inversely associated with sE-selectin. Participants with low levels of HDL-C (<40 mg/dL) or HDL-P (<25th percentile) showed 3%-12% higher mean levels of soluble vascular cell adhesion molecule and compared with those above these levels (all P < .01). CONCLUSION: Coupled with previous evidence, our findings suggest a modest to moderate relation of HDL and circulating levels of endothelial activation markers in humans. Whether this relationship may have clinical implications in suppressing atherogenesis or coronary heart disease development requires additional research.

Elevated Levels of Adhesion Proteins Are Associated With Low Ankle-Brachial Index.

Inflammation plays a pivotal role in peripheral artery disease (PAD). Cellular adhesion proteins mediate the interaction of leukocytes with endothelial cells during inflammation. To determine the association of cellular adhesion molecules with ankle-brachial index (ABI) and ABI category (≤1.0 vs >1.0) in a diverse population, 15 adhesion proteins were measured in the Multi-Ethnic Study of Atherosclerosis (MESA). To assess multivariable associations of each protein with ABI and ABI category, linear and logistic regression was used, respectively. Among 2364 participants, 23 presented with poorly compressible arteries (ABI > 1.4) and were excluded and 261 had ABI ≤ 1.0. Adjusting for traditional risk factors, elevated levels of soluble P-selectin, hepatocyte growth factor, and secretory leukocyte protease inhibitor were associated with lower ABI ( P = .0004, .001, and .002, respectively). Per each standard deviation of protein, we found 26%, 20%, and 19% greater odds of lower ABI category ( P = .001, .01, and .02, respectively). Further investigation into the adhesion pathway may shed new light on biological mechanisms implicated in PAD.