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1.
Am Heart J ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972336

RESUMO

BACKGROUND: Reflecting clinical trial data showing improved outcomes with lower LDL-C levels, guidelines across the globe are increasingly recommending a goal of LDL-C <55 mg/dL in persons with atherosclerotic cardiovascular disease (ASCVD). What proportion of patients with ASCVD are already meeting those goals in the US remains understudied. METHODS: Using electronic health record data from 8 large US health systems, we evaluated lipid-lowering therapy (LLT), LDL-C levels, and factors associated with an LDL-C <55 mg/dL in persons with ASCVD treated between 1/1/2021-12/31/2021. Multivariable modeling was used to evaluate factors associated with achievement of an LDL-C <55 mg/dL. RESULTS: Among 167,899 eligible patients, 22.6% (38,016) had an LDL-C <55 mg/dL. While 76.1% of individuals overall were on a statin, only 38.2% were on a high-intensity statin,;5.9% were on ezetimibe, and 1.7% were on a PCSK9i monoclonal antibody (mAb). Factors associated with lower likelihood of achieving an LDL-C <55 mg/dL included: younger age (odds ratio [OR] 0.91 per 10y), female sex (OR 0.69), Black race (OR 0.76), and non-coronary artery disease forms of ASCVD including peripheral artery disease (OR 0.72) and cerebrovascular disease (OR 0.85), while high-intensity statin use was associated with increased odds of LDL-C <55 mg/dL (OR 1.55). Combination therapy (statin+ezetimibe or statin+PCSK9i mAb) was rare (4.4% and 0.5%, respectively) and was associated with higher odds of an LDL-C <55 mg/dL (OR 1.39 and 3.13, respectively). CONCLUSION: Less than a quarter of US patients with ASCVD in community practice are already achieving an LDL-C <55 mg/dL. Marked increases in utilization of both high intensity statins and combination therapy with non-statin therapy will be needed to achieve LDL-C levels <55 mg/dL at the population level in secondary prevention.

2.
Circulation ; 150(1): 62-79, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38950110

RESUMO

Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic cardiovascular disease risk, apoB measurement has not become widely adopted into routine clinical practice. One barrier for use of apoB measurement is lack of consistent guidance for clinicians on how to interpret and apply apoB results in clinical context. Whereas guidelines have often provided clear low-density lipoprotein cholesterol targets or triggers to initiate treatment change, consistent targets for apoB are lacking. In this review, we synthesize existing data regarding the epidemiology of apoB by comparing guideline recommendations regarding use of apoB measurement, describing population percentiles of apoB relative to low-density lipoprotein cholesterol levels, summarizing studies of discordance between low-density lipoprotein cholesterol and apoB levels, and evaluating apoB levels in clinical trials of lipid-lowering therapy to guide potential treatment targets. We propose evidence-guided apoB thresholds for use in cholesterol management and clinical care.


Assuntos
Apolipoproteínas B , LDL-Colesterol , Humanos , Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Guias de Prática Clínica como Assunto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Biomarcadores/sangue , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Apolipoproteína B-100
3.
JAMA Cardiol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865115

RESUMO

Importance: Although apolipoprotein B (apoB) is a superior marker of lipid-related risk compared with low-density lipoprotein cholesterol (LDL-C), few data exist to translate the goals and thresholds from LDL-C to their apoB equivalent. In addition, although current American College of Cardiology/American Heart Association guidelines provide a relative indication for apoB measurement among individuals with hypertriglyceridemia, whether discordance is limited to those subgroups is unknown. Objectives: To assess the variability in apoB level across the spectrum of LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels and evaluate whether discordance between apoB and LDL-C or non-HDL-C is limited to specifiable subgroups. Design, Setting, and Participants: This cross-sectional study used data from a nationally representative sample of 12 688 adult participants not using statins in the National Health and Nutrition Examination Survey between 2005 and 2016. Statistical analysis was performed from April 2023 to February 2024. Main Outcomes and Measures: Quantile regression was used to assess the population distribution of apoB across LDL-C or non-HDL-C levels. Discordance between apoB and LDL-C was the difference between measured apoB and median apoB levels for an individual's LDL-C level. Discordance was evaluated by age, sex, race and ethnicity, obesity, diabetes, triglyceride level, hemoglobin A1c level, body mass index (BMI), statin use, and metabolic health (defined as a BMI between 18.5 and 24.9, triglyceride level <150 mg/dL, and no diabetes). Results: Among the sample of 12 688 participants (median age, 41.0 years [IQR, 29.0-54.0 years]; 52.9% women) for LDL-C values of 55, 70, 100, and 190 mg/dL, the corresponding population median apoB levels were 49, 60, 80, and 140 mg/dL, respectively. For given levels of LDL-C, a range of apoB values was observed. At an LDL-C level of 100 mg/dL, the 95% population distribution of apoB ranged from 66 mg/dL to 99 mg/dL. ApoB variability was highest for LDL-C values estimated using the Friedewald equation, lower when using Sampson or Martin-Hopkins equations, and lowest for non-HDL-C. Although individuals with metabolic risk factors were more likely to have discordantly high apoB levels (ie, had higher median observed apoB levels relative to what was estimated based on LDL-C), significant variability in apoB levels was observed even among metabolically healthy individuals. Conclusions and Relevance: This study suggests that even metabolically healthy individuals may have discordantly high apoB levels relative to LDL-C or non-HDL-C levels. The current guideline approach for apoB testing only for those with hypertriglyceridemia appears too narrow. Population percentile data can be used to translate LDL-C goals and thresholds to their apoB equivalent to facilitate clinical adoption.

4.
J Am Coll Cardiol ; 83(25): 2643-2654, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38897674

RESUMO

BACKGROUND: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. OBJECTIVES: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. METHODS: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. RESULTS: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). CONCLUSIONS: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases.


Assuntos
Doenças Autoimunes , Doença da Artéria Coronariana , Sistema de Registros , Índice de Gravidade de Doença , Humanos , Doença da Artéria Coronariana/epidemiologia , Masculino , Feminino , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/complicações , Pessoa de Meia-Idade , Idoso , Dinamarca/epidemiologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Fatores de Risco , Isquemia Miocárdica/epidemiologia , Seguimentos
5.
Am Heart J ; 274: 32-45, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38705341

RESUMO

BACKGROUND: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. METHODS AND RESULTS: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. CONCLUSION: These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.


Assuntos
Anticolesterolemiantes , Aterosclerose , LDL-Colesterol , Humanos , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Método Duplo-Cego , LDL-Colesterol/sangue , Masculino , Feminino , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , HDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteína(a)/sangue , Pessoa de Meia-Idade
6.
Am J Prev Cardiol ; 18: 100669, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38681065

RESUMO

Objective: Aspirin has been used for primary prevention of atherosclerotic cardiovascular disease (ASCVD) for decades, but this indication has become controversial with recent trial data. The 2022 US Preventive Services Task Force (USPSTF) provided a recommendation to consider aspirin use for primary prevention in adults 40-59 years with a 10-year ASCVD risk ≥10 % and not at increased risk of bleeding, yet population estimates for the impact of this recommendation are unknown. The objective of this study is to determine the prevalence and demographics of the US population who meet eligibility criteria for aspirin under the new 2022 USPSTF guidelines. Methods: This is a serial cross-sectional study using data from the 2011-March 2020 National Health and Nutrition Examination Survey (NHANES) database. Individuals aged 40-59 years without a self-reported history of ASCVD were included. 10-year estimated ASCVD risk ≥10 % as calculated by the Pooled Cohort Equations (PCE) and increased bleeding risk determined using variables adapted from USPSTF guidelines were further applied as inclusion and exclusion criteria, respectively. The weighted frequencies of US adults aged 40-59 years qualifying for primary prevention aspirin, subgrouped by gender, age, and race/ethnicity, were calculated. Results: Among 72,840,734 US individuals aged 40-59 years, 7.2 million (10 %) are eligible for consideration of primary prevention aspirin by PCE criteria. Of these, approximately 30 % would be potentially excluded based on increased bleeding risks, resulting in a net eligible cohort of 5 million. This represents 7 % of US adults aged 40-59 years and only 2.6 % of adults ≥18 years. Men, age 50-59 years, and Black race have higher proportions meeting aspirin use eligibility. Conclusions: The overall prevalence of US individuals who qualify for aspirin for primary prevention under the 2022 USPSTF guidelines is modest, with larger proportional eligibility among men, older age, and Black individuals.

7.
J Am Coll Cardiol ; 83(16): 1557-1567, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38631775

RESUMO

Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease risk stratification. The nongated, noncontrast chest computed tomography scan (NCCT) has emerged as a source of CAC characterization with tremendous potential due to the high volume of NCCT scans. Application of incidental CAC characterization from NCCT has raised questions around score accuracy, standardization of methodology including the possibility of deep learning to automate the process, and the risk stratification potential of an NCCT-derived score. In this review, the authors aim to summarize the role of NCCT-derived CAC in preventive cardiovascular health today as well as explore future avenues for eventual clinical applicability in specific patient populations and broader health systems.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Calcificação Vascular , Humanos , Cálcio , Tomografia Computadorizada por Raios X/métodos , Coração , Vasos Coronários , Fatores de Risco , Angiografia Coronária
8.
Am J Cardiol ; 221: 19-28, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38583700

RESUMO

Cardiogenic shock after acute myocardial infarction (AMI-CS) carries significant mortality despite advances in revascularization and mechanical circulatory support. We sought to identify the process-based and structural characteristics of centers with lower mortality in AMI-CS. We analyzed 16,337 AMI-CS cases across 440 centers enrolled in the National Cardiovascular Data Registry's Chest Pain-MI Registry, a retrospective cohort database, between January 1, 2015, and December 31, 2018. Centers were stratified across tertiles of risk-adjusted in-hospital mortality rate (RAMR) for comparison. Risk-adjusted multivariable logistic regression was also performed to identify hospital-level characteristics associated with decreased mortality. The median participant age was 66 (interquartile range 57 to 75) years, and 33.0% (n = 5,390) were women. The median RAMR was 33.4% (interquartile range 26.0% to 40.0%) and ranged from 26.9% to 50.2% across tertiles. Even after risk adjustment, lower-RAMR centers saw patients with fewer co-morbidities. Lower-RAMR centers performed more revascularization (92.8% vs 90.6% vs 85.9%, p <0.001) and demonstrated better adherence to associated process measures. Left ventricular assist device capability (odds ratio [OR] 0.78 [0.67 to 0.92], p = 0.002), more frequent revascularization (OR 0.93 [0.88 to 0.98], p = 0.006), and higher AMI-CS volume (OR 0.95 [0.91 to 0.99], p = 0.009) were associated with lower in-hospital mortality. However, several such characteristics were not more frequently observed at low-RAMR centers, despite potentially reflecting greater institutional experience or resources. This may reflect the heterogeneity of AMI-CS even after risk adjustment. In conclusion, low-RAMR centers do not necessarily exhibit factors associated with decreased mortality in AMI-CS, which may reflect the challenges in performing outcomes research in this complex population.


Assuntos
Mortalidade Hospitalar , Infarto do Miocárdio , Sistema de Registros , Choque Cardiogênico , Humanos , Feminino , Masculino , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Pessoa de Meia-Idade , Idoso , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Hospitais com Alto Volume de Atendimentos , Revascularização Miocárdica/estatística & dados numéricos
9.
J Am Heart Assoc ; 13(7): e032678, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38533942

RESUMO

BACKGROUND: Many individuals eligible for statin therapy decline treatment, often due to fear of adverse effects. Misinformation about statins is common and drives statin reluctance, but its prevalence on social media platforms, such as Twitter (now X) remains unclear. Social media bots are known to proliferate medical misinformation, but their involvement in statin-related discourse is unknown. This study examined temporal trends in volume, author type (bot or human), and sentiment of statin-related Twitter posts (tweets). METHODS AND RESULTS: We analyzed original tweets with statin-related terms from 2010 to 2022 using a machine learning-derived classifier to determine the author's bot probability, natural language processing to assign each tweet a negative or positive sentiment, and manual qualitative analysis to identify statin skepticism in a random sample of all tweets and in highly influential tweets. We identified 1 155 735 original statin-related tweets. Bots produced 333 689 (28.9%), humans produced 699 876 (60.6%), and intermediate probability accounts produced 104 966 (9.1%). Over time, the proportion of bot tweets decreased from 47.8% to 11.3%, and human tweets increased from 43.6% to 79.8%. The proportion of negative-sentiment tweets increased from 27.8% to 43.4% for bots and 30.9% to 38.4% for humans. Manually coded statin skepticism increased from 8.0% to 19.0% for bots and from 26.0% to 40.0% for humans. CONCLUSIONS: Over the past decade, humans have overtaken bots as generators of statin-related content on Twitter. Negative sentiment and statin skepticism have increased across all user types. Twitter may be an important forum to combat statin-related misinformation.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Mídias Sociais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Software , Comunicação , Processamento de Linguagem Natural
11.
JAMA Cardiol ; 9(1): 55-62, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38055247

RESUMO

Importance: Use of race-specific risk prediction in clinical medicine is being questioned. Yet, the most commonly used prediction tool for atherosclerotic cardiovascular disease (ASCVD)-pooled cohort risk equations (PCEs)-uses race stratification. Objective: To quantify the incremental value of race-specific PCEs and determine whether adding social determinants of health (SDOH) instead of race improves model performance. Design, Setting, and Participants: Included in this analysis were participants from the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort study. Participants were aged 45 to 79 years, without ASCVD, and with low-density lipoprotein cholesterol level of 70 to 189 mg/dL or non-high-density lipoprotein cholesterol level of 100 to 219 mg/dL at baseline during the period of 2003 to 2007. Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke. Study data were analyzed from July 2022 to February 2023. Main outcome/measures: Discrimination (C statistic, Net Reclassification Index [NRI]), and calibration (plots, Nam D'Agostino test statistic comparing observed to predicted events) were assessed for the original PCE, then for a set of best-fit, race-stratified equations including the same variables as in the PCE (model C), best-fit equations without race stratification (model D), and best-fit equations without race stratification but including SDOH as covariates (model E). Results: This study included 11 638 participants (mean [SD] age, 61.8 [8.3] years; 6764 female [58.1%]) from the REGARDS cohort. Across all strata (Black female, Black male, White female, and White male participants), C statistics did not change substantively compared with model C (Black female, 0.71; 95% CI, 0.68-0.75; Black male, 0.68; 95% CI, 0.64-0.73; White female, 0.77; 95% CI, 0.74-0.81; White male, 0.68; 95% CI, 0.64-0.71), in model D (Black female, 0.71; 95% CI, 0.67-0.75; Black male, 0.68; 95% CI, 0.63-0.72; White female, 0.76; 95% CI, 0.73-0.80; White male, 0.68; 95% CI, 0.65-0.71), or in model E (Black female, 0.72; 95% CI, 0.68-0.76; Black male, 0.68; 95% CI, 0.64-0.72; White female, 0.77; 95% CI, 0.74-0.80; White male, 0.68; 95% CI, 0.65-0.71). Comparing model D with E using the NRI showed a net percentage decline in the correct assignment to higher risk for male but not female individuals. The Nam D'Agostino test was not significant for all race-sex strata in each model series, indicating good calibration in all groups. Conclusions: Results of this cohort study suggest that PCE performed well overall but had poorer performance in both BM and WM participants compared with female participants regardless of race in the REGARDS cohort. Removal of race or the addition of SDOH did not improve model performance in any subgroup.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Racismo , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Estudos de Coortes , Estudos Prospectivos , Determinantes Sociais da Saúde , Medição de Risco/métodos , Aterosclerose/epidemiologia , Acidente Vascular Cerebral/epidemiologia
12.
J Am Heart Assoc ; 12(21): e031160, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37929707

RESUMO

Background High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. Methods and Results Seven HDL size-based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi-Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow-up (average 8-10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81-0.94]; H4 0.89 [95% CI, 0.82-0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88-0.99]; H4 0.91 [95% CI, 0.85-0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. Conclusions Two of 7 HDL size-based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.


Assuntos
Aterosclerose , Infarto do Miocárdio , Humanos , Feminino , Pessoa de Meia-Idade , Lipoproteínas HDL , HDL-Colesterol , Fatores de Risco
13.
JAMA ; 330(21): 2075-2083, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37952254

RESUMO

Importance: Epidemiological and genetic data have implicated lipoprotein(a) as a potentially modifiable risk factor for atherosclerotic disease and aortic stenosis, but there are no approved pharmacological treatments. Objectives: To assess the safety, tolerability, pharmacokinetics, and effects of lepodisiran on lipoprotein(a) concentrations after single doses of the drug; lepodisiran is a short interfering RNA directed at hepatic synthesis of apolipoprotein(a), an essential component necessary for assembly of lipoprotein(a) particles. Design, Setting, and Participants: A single ascending-dose trial conducted at 5 clinical research sites in the US and Singapore that enrolled 48 adults without cardiovascular disease and with lipoprotein(a) serum concentrations of 75 nmol/L or greater (or ≥30 mg/dL) between November 18, 2020, and December 7, 2021; the last follow-up visit occurred on November 9, 2022. Interventions: Participants were randomized to receive placebo or a single dose of lepodisiran (4 mg, 12 mg, 32 mg, 96 mg, 304 mg, or 608 mg) administered subcutaneously. Main Outcomes and Measures: The primary outcome was the safety and tolerability of the single ascending doses of lepodisiran. The secondary outcomes included plasma levels of lepodisiran for 168 days after dose administration and changes in fasting lipoprotein(a) serum concentrations through a maximum follow-up of 336 days (48 weeks). Results: Of the 48 participants enrolled (mean age, 46.8 [SD, 11.6] years; 35% were women), 1 serious adverse event occurred. The plasma concentrations of lepodisiran reached peak levels within 10.5 hours and were undetectable by 48 hours. The median baseline lipoprotein(a) concentration was 111 nmol/L (IQR, 78 to 134 nmol/L) in the placebo group, 78 nmol/L (IQR, 50 to 152 nmol/L) in the 4 mg of lepodisiran group, 97 nmol/L (IQR, 86 to 107 nmol/L) in the 12-mg dose group, 120 nmol/L (IQR, 110 to 188 nmol/L) in the 32-mg dose group, 167 nmol/L (IQR, 124 to 189 nmol/L) in the 96-mg dose group, 96 nmol/L (IQR, 72 to 132 nmol/L) in the 304-mg dose group, and 130 nmol/L (IQR, 87 to 151 nmol/L) in the 608-mg dose group. The maximal median change in lipoprotein(a) concentration was -5% (IQR, -16% to 11%) in the placebo group, -41% (IQR, -47% to -20%) in the 4 mg of lepodisiran group, -59% (IQR, -66% to -53%) in the 12-mg dose group, -76% (IQR, -76% to -75%) in the 32-mg dose group, -90% (IQR, -94% to -85%) in the 96-mg dose group, -96% (IQR, -98% to -95%) in the 304-mg dose group, and -97% (IQR, -98% to -96%) in the 608-mg dose group. At day 337, the median change in lipoprotein(a) concentration was -94% (IQR, -94% to -85%) in the 608 mg of lepodisiran group. Conclusions and Relevance: In this phase 1 study of 48 participants with elevated lipoprotein(a) levels, lepodisiran was well tolerated and produced dose-dependent, long-duration reductions in serum lipoprotein(a) concentrations. The findings support further study of lepodisiran. Trial Registration: ClinicalTrials.gov Identifier: NCT04914546.


Assuntos
Apolipoproteínas A , Lipoproteína(a) , RNA Interferente Pequeno , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Lipoproteína(a)/antagonistas & inibidores , Lipoproteína(a)/sangue , Fatores de Risco , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/efeitos adversos , RNA Interferente Pequeno/uso terapêutico , Singapura , Apolipoproteínas A/biossíntese , Fígado/metabolismo , Administração Cutânea , Estados Unidos
14.
JAMA Cardiol ; 8(12): 1185-1187, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910086

RESUMO

This cross-sectional study compares the prevalence, awareness, and treatment of elevated low-density lipoprotein (LDL) cholesterol in US adults in 1999-2000 vs 2017-2020.


Assuntos
Hipercolesterolemia , Adulto , Humanos , LDL-Colesterol , Prevalência , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/epidemiologia , Inquéritos Nutricionais
15.
J Cardiovasc Comput Tomogr ; 17(6): 453-458, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37863760

RESUMO

INTRODUCTION: CAC can be detected on routine chest computed tomography (CT) scans and may contribute to CVD risk estimation, but the accuracy of visual CAC scoring may be affected by the specialty of the interpreting radiologist and/or the use of contrast. METHODS: The accuracy of visual CAC estimation on non-gated CT scans was evaluated at UT Southwestern Medical Center (UTSW) and Parkland Health and Hospital System (PHHS). All adults who underwent CAC scanning and a non-gated CT scan within 6 months were identified and the scores from the two CTs were compared overall and stratified by type of reader and whether contrast was used. Visual CAC categories of none, small, moderate, and large were compared to CAC â€‹= â€‹0, 1-99, 100-399, and ≥400, respectively. RESULTS: From 2016 to 2021, 934 patients (mean age 60 â€‹± â€‹12 â€‹y, 43% male, 61% White, 34% Black, 24% Hispanic, 54% from PHHS) had both CT scans. Of these, 441 (47%) had no CAC, 278 (30%) small, 147 (16%) moderate, and 66 (7%) large CAC on non-gated CT. Visual CAC estimates were highly correlated with CAC scores (Kendalls tau-b â€‹= â€‹0.76, p â€‹< â€‹0.0001). Among those with no visual CAC, 76% had CAC â€‹= â€‹0 (72% of contrast-enhanced vs 85% of non-contrast scans, 88% of scans interpreted by CT radiologist vs 78% of those interpreted by other radiologist). In those with moderate-to-large visual CAC, 99% had CAC >0 and 88% had CAC ≥100, including 89% of those with contrast, 90% of those without contrast, 80% of those read by a CT radiologist, and 88% of those read by a non-CT radiologist. DISCUSSION: Visual CAC estimates on non-gated CT scans are concordant with Agatston score categories from cardiac CT scans. A lack of visual CAC on non-gated CT scans may not be sufficient to "de-risk" patients, particularly for contrast-enhanced scans and those read by non-CT radiologists. However, the presence of moderate-to-large CAC, including on contrasted scans and regardless of radiologist type, is highly predictive of CAC and may be used to identify high-risk patients for prevention interventions.


Assuntos
Doença da Artéria Coronariana , Calcificação Vascular , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Vasos Coronários/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Cálcio , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X/métodos , Calcificação Vascular/diagnóstico por imagem , Angiografia Coronária/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-37771735

RESUMO

Background: Peri-diagnostic vaccination contemporaneous with SARS-CoV-2 infection might boost antiviral immunity and improve patient outcomes. We investigated, among previously unvaccinated patients, whether vaccination (with the Pfizer, Moderna, or J&J vaccines) during the week before or after a positive COVID-19 test was associated with altered 30-day patient outcomes. Methods: Using a deidentified longitudinal EHR repository, we selected all previously unvaccinated adults who initially tested positive for SARS-CoV-2 between December 11, 2020 (the date of vaccine emergency use approval) and December 19, 2021. We assessed whether vaccination between days -7 and +7 of a positive test affected outcomes. The primary measure was progression to a more severe disease outcome within 30 days of diagnosis using the following hierarchy: hospitalization, intensive care, or death. Results: Among 60,031 hospitalized patients, 543 (0.91%) were initially vaccinated at the time of diagnosis and 59,488 (99.09%) remained unvaccinated during the period of interest. Among 316,337 nonhospitalized patients, 2,844 (0.90%) were initially vaccinated and 313,493 (99.1%) remained unvaccinated. In both analyses, individuals receiving vaccines were older, more often located in the northeast, more commonly insured by Medicare, and more burdened by comorbidities. Among previously unvaccinated patients, there was no association between receiving an initial vaccine dose between days -7 and +7 of diagnosis and progression to more severe disease within 30 days compared to patients who did not receive vaccines. Conclusions: Immunization during acute SARS-CoV-2 infection does not appear associated with clinical progression during the acute infectious period.

17.
JAMA Cardiol ; 8(10): 984-988, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37610733

RESUMO

Importance: One in 5 US adults older than 60 years takes fish oil supplements often for heart health despite multiple randomized clinical trials showing no data for cardiovascular benefit for supplement-range doses. Statements on the supplement labels may influence consumer beliefs about health benefits. Objectives: To evaluate health claims made on the labels of fish oil supplements in the US, and to examine doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in commonly available formulations. Design, Setting, and Participants: This cross-sectional study used data from labels of on-market fish oil (and nonfish ω-3 fatty acid) supplements obtained from the National Institutes of Health Dietary Supplement Label Database. The study was conducted and data analyzed from February to June 2022. Main Outcome and Measures: The frequency and types of health claims made on fish oil labels (US Food and Drug Administration [FDA]-reviewed qualified health claim vs a structure/function claim) and the organ system referenced were evaluated. The total daily doses of combined EPA and DHA (EPA+DHA) were assessed for supplements from 16 leading manufacturers and retailers. Results: Across 2819 unique fish oil supplements, 2082 (73.9%) made at least 1 health claim. Of these, only 399 (19.2%) used an FDA-approved qualified health claim; the rest (1683 [80.8%]) made only structure/function claims (eg, "promotes heart health"). Cardiovascular health claims were the most common (1747 [62.0%]). Across 16 leading brands/manufacturers, 255 fish oil supplements were identified. Among these, substantial variability was found in the daily dose of EPA (median [IQR], 340 [135-647] mg/d), DHA (median [IQR], 270 [140-500] mg/d), and total EPA+DHA (median [IQR], 600 [300-1100] mg/d). Only 24 of 255 supplements (9.4%) evaluated contained a daily dose of 2 g or more EPA+DHA. Conclusions: Results of this cross-sectional study suggest that the majority of fish oil supplement labels make health claims, usually in the form of structure/function claims, that imply a health benefit across a variety of organ systems despite a lack of trial data showing efficacy. Significant heterogeneity exists in the daily dose of EPA+DHA in available supplements, leading to potential variability in safety and efficacy between supplements. Increasing regulation of dietary supplement labeling may be needed to prevent consumer misinformation.

19.
Circ Cardiovasc Qual Outcomes ; 16(8): 533-543, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37529931

RESUMO

BACKGROUND: Many patients with atherosclerotic cardiovascular disease (ASCVD) are not on guideline-recommended statin therapy. We evaluated utilization of statins and other lipid-lowering therapy (LLT), and changes in low-density lipoprotein cholesterol (LDL-C), among patients with ASCVD over a 1-year period. METHODS: LLT and LDL-C levels at the first outpatient visit (January 1, 2017-December 31, 2018) and 1-year follow-up were evaluated using data from Cerner Real-World Data, an electronic health record-derived data set from 92 US health systems. Logistic regression was used to evaluate factors associated with high-intensity statin use. RESULTS: We identified 322 153 patients with ASCVD (median age 69 years, 58.8% men, 81.8% White). Overall, 76.1% of patients were on statins, with only 39.4% on high-intensity statins. Men were more likely to receive high-intensity statins than women (multivariable-adjusted odds ratio, 1.34 [95% CI, 1.30-1.38]). Increasing age was associated with lower odds of statin use (odds ratio, 0.79 per 5-year increase at 60 years [95% CI, 0.78-0.81]). Patients with peripheral artery disease (odds ratio, 0.40 [95% CI, 0.37-0.42]) and cerebrovascular disease (odds ratio, 0.75 [95% CI, 0.70-0.80]) had lower odds of using high-intensity statins than those with coronary artery disease. At baseline, most patients (61.3%) had elevated LDL-C (≥70 mg/dL), including 59.8% of those on low/moderate-intensity statins and 76.1% on no statin; only 45.3% achieved an LDL-C <70 mg/dL at 1 year. Nonstatin LLT use was low (ezetimibe, 4.4%; proprotein convertase subtilisin/kexin type 9 inhibitors, 0.7%). Among patients on no statin or low/moderate-intensity statin at baseline, 14.8% and 13.4%, respectively, were on high-intensity statins at 1 year. CONCLUSIONS: Among patients with ASCVD in routine care, high-intensity statins are underutilized, and uptitration and use of nonstatin therapy are uncommon. Women, older adults, and individuals with noncardiac ASCVD are particularly undertreated. Concerted efforts are needed to address therapeutic inertia for lipid management in patients with ASCVD.


Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Pré-Escolar , LDL-Colesterol , Prevenção Secundária , Estudos Retrospectivos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Ezetimiba/uso terapêutico , Doenças Cardiovasculares/prevenção & controle
20.
J Clin Lipidol ; 17(5): 688-693, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37599197

RESUMO

Statin use among younger adults at high atherosclerotic cardiovascular disease (ASCVD) risk compared with older adults at the same risk is unclear. We determined prevalent statin use by 10-year ASCVD risk and age among US participants aged 40-75 eligible for risk-indicated primary prevention statins from the 2013-2020 National Health and Nutrition Examination Survey cycles. Among 3,503 participants, statin use by ASCVD risk (5-<7.5%, 7.5-<20%, and ≥20%) was 9.4%, 9.0%, and 12.2% among those age 40-54 compared to 22.0%, 23.9%, and 14.3% among adults 55-64 years and 39.3%, 33.6%, and 38.1% age 65-75 years. After adjusting for sociodemographic and healthcare access, the prevalence ratio (vs. 65-75 years) for statin use among adults with an ASCVD risk of 7.5-<20% age 40-54 years was 0.40 (95% confidence interval [CI] 0.39,0.41) and 0.87 (95% CI 0.87,0.88) for adults 55-64 years. Among high ASCVD-risk adults aged 40-75 years, primary prevention statin use was lower among adults <65 years despite similar ASCVD risk as older adults.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inquéritos Nutricionais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Aterosclerose/epidemiologia , Prevenção Primária , Fatores de Risco
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