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JACC. Advances Jun 2024Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD).
BACKGROUND
Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD).
OBJECTIVES
The authors assessed differences in Lp(a) testing and levels by disaggregated race, ethnicity, and ASCVD risk.
METHODS
This was a retrospective cohort study of patients from a large California health care system from 2010 to 2021. Eligible individuals were ≥18 years old, with ≥2 primary care visits, and complete race and ethnicity data who underwent Lp(a) testing. Race and ethnicity were self-reported and categorized as follows: non-Hispanic (NH) White, NH-Black, Hispanic (Mexican, Puerto Rican, other), NH-Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, other). Logistic regression models tested associations between elevated Lp(a) (≥50 mg/dL) and race, ethnicity, and ASCVD risk.
RESULTS
13,689 (0.9%) individuals underwent Lp(a) testing with a mean age of 54.6 ± 13.8 years, 49% female, 28.8% NH Asian. Over one-third of those tested had Lp(a) levels ≥50 mg/dL, ranging from 30.7% of Mexican patients to 62.6% of NH-Black patients. The ASCVD risk of those tested varied by race: 73.6% of Asian Indian individuals had <5% 10-year risk, whereas 27.2% of NH-Black had established ASCVD. Lp(a) prevalence ≥50 mg/dL increased across the ASCVD risk spectrum. After adjustment, Hispanic (OR: 0.76 [95% CI: 0.66-0.88]) and Asian (OR: 0.88 [95% CI: 0.81-0.96]) had lower odds of Lp(a) ≥50 mg/dL, whereas Black individuals had higher odds (OR: 2.46 [95% CI: 1.97-3.07]).
CONCLUSIONS
Lp(a) testing is performed infrequently. Of those tested, Lp(a) levels were frequently elevated and differed significantly across disaggregated race and ethnicity groups. The prevalence of elevated Lp(a) increased with increasing ASCVD risk, with significant variation by race and ethnicity.
PubMed: 38938854
DOI: 10.1016/j.jacadv.2024.100940 -
JACC. Advances Jun 2024Heart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV)...
BACKGROUND
Heart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV) loop analysis can be performed noninvasively using cardiovascular magnetic resonance (CMR) imaging to assess cardiac thermodynamic efficiency.
OBJECTIVES
The aim of the study was to investigate whether noninvasive PV loop parameters, derived from CMR, could predict major adverse cardiac events (MACE) in HFrEF patients.
METHODS
PV loop parameters (stroke work, ventricular efficiency, external power, contractility, and energy per ejected volume) were computed from CMR cine images and brachial blood pressure. The primary end point was MACE (cardiovascular death, heart failure (HF) hospitalization, myocardial infarction, revascularization, ventricular tachycardia/fibrillation, heart transplantation, or left ventricular assist device implantation within 5 years). Associations between PV loop parameters and MACE were evaluated using multivariable Cox regression.
RESULTS
One hundred and sixty-four HFrEF patients (left ventricular ejection fraction ≤40%, age 63 [IQR: 55-70] years, 79% male) who underwent clinical CMR examination between 2004 and 2014 were included. Eighty-eight patients (54%) experienced at least one MACE after an average of 2.8 years. Unadjusted models demonstrated a significant association between MACE and all PV loop parameters ( < 0.05 for all), HF etiology ( < 0.001), left ventricular ejection fraction ( = 0.003), global longitudinal strain ( < 0.001), and N-terminal prohormone of brain natriuretic peptide level ( = 0.001). In the multivariable Cox regression analysis adjusted for age, sex, hypertension, diabetes, and HF etiology, ventricular efficiency was associated with MACE (HR: 1.04 (95% CI: 1.01-1.08) per-% decrease, = 0.01).
CONCLUSIONS
Ventricular efficiency, derived from noninvasive PV loop analysis from standard CMR scans, is associated with MACE in patients with HFrEF.
PubMed: 38938852
DOI: 10.1016/j.jacadv.2024.100946 -
JACC. Advances Mar 2024Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the...
BACKGROUND
Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation.
OBJECTIVES
The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin.
METHODS
Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21.
RESULTS
Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low.
CONCLUSIONS
Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.
PubMed: 38938844
DOI: 10.1016/j.jacadv.2023.100780 -
JACC. Advances Mar 2024Hypertensive disorders of pregnancy (HDP) complicate 13% to 15% of pregnancies in the United States. Historically marginalized communities are at increased risk, with... (Review)
Review
Hypertensive disorders of pregnancy (HDP) complicate 13% to 15% of pregnancies in the United States. Historically marginalized communities are at increased risk, with preeclampsia and eclampsia being the leading cause of death in this population. Pregnant individuals with HDP require more frequent and intensive monitoring throughout the antepartum period outside of routine standard of care prenatal visits. Additionally, acute rises in blood pressure often occur 3 to 6 days postpartum and are challenging to identify and treat, as most postpartum individuals are usually scheduled for their first visit 6 weeks after delivery. Thus, a multifaceted approach is necessary to improve recognition and treatment of HDP throughout the peripartum course. There are limited studies investigating interventions for the management of HDP, especially within the United States, where maternal mortality is rising, and in higher-risk groups. We review the state of current management of HDP and innovative strategies such as blood pressure self-monitoring, telemedicine, and community health worker intervention.
PubMed: 38938826
DOI: 10.1016/j.jacadv.2024.100864 -
JACC. Advances Nov 2023
PubMed: 38938727
DOI: 10.1016/j.jacadv.2023.100663 -
JACC. Advances Nov 2023
PubMed: 38938715
DOI: 10.1016/j.jacadv.2023.100674 -
Frontiers in Immunology 2024Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently...
Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.
Topics: Humans; Salivary Glands; Autoantibodies; Myositis; Female; Male; Lung; Middle Aged; Bronchoalveolar Lavage Fluid; Adult; B-Lymphocytes; Lung Diseases, Interstitial; Autoantigens; Antibodies, Antinuclear; Aged
PubMed: 38938569
DOI: 10.3389/fimmu.2024.1265792 -
CHEST Critical Care Jun 2024Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of...
BACKGROUND
Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis.
RESEARCH QUESTION
Are altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis?
STUDY DESIGN AND METHODS
We assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to measure directly baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated adenosine triphosphate-linked, spare respiratory capacity, and nonmitochondrial oxygen consumption rate from the measured values.
RESULTS
Maximum oxygen consumption was highest in patients with coma, as was spare respiratory capacity and extracellular acidification rate in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment score without the neurologic component, and preexisting cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics.
INTERPRETATION
In this single-center exploratory prospective cohort study, we found that increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.
PubMed: 38938510
DOI: 10.1016/j.chstcc.2024.100076 -
JACC. Advances Dec 2023Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the...
BACKGROUND
Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction.
OBJECTIVES
This study examined the relationship between vital reproductive factors (parity, pregnancy, age at menopause, and use of hormone replacement therapy [HRT]) with interstitial myocardial fibrosis (IMF) and myocardial scar measured by cardiac magnetic resonance imaging (CMR) T1 mapping and late gadolinium enhancement, respectively.
METHODS
There were 596 female participants (mean age 67 ± 8 years) enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) who had complete parity data and underwent CMR. Parity was categorized as 0 live births, 1 to 2, 3 to 4, and ≥5 live births. Multivariable regression models were constructed to assess the associations of parity status, history of null gravidity, age at menopause and HRT with CMR obtained measures of IMF (extracellular volume [ECV], native-T1 time) and myocardial scar.
RESULTS
Women with a history of nulliparity had greater ECV% (β = 0.95 ± 0.28, = 0.001) and native-T1 ms (β = 10.6 ± 4.9, = 0.03) than those who had 1 to 2 live births. These associations were independent of age, traditional cardiovascular risk factors, and interim cardiovascular events. Similar associations were found for women with a history of null gravidity compared to those with a history of pregnancy (ECV% [β = 0.7 ± 0.3, = 0.02] and native-T1 ms [β = 10.6 ± 5.2, = 0.04]). There was no association between age at menopause and HRT with markers of IMF. There were no associations between parity status, null gravidity, and age of menopause with the presence of myocardial scar; however, those who used HRT were independently associated with a lesser risk of myocardial scar (OR: 0.20; 95% CI: 0.05-0.82).
CONCLUSIONS
In a multiethnic cohort, women with a history of nulliparity or null gravidity had greater IMF defined by CMR, while those who used HRT were less likely to have myocardial scar.
PubMed: 38938498
DOI: 10.1016/j.jacadv.2023.100703 -
JACC. Advances Dec 2023
PubMed: 38938497
DOI: 10.1016/j.jacadv.2023.100678