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2.
PLoS One ; 16(2): e0246073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33561176

RESUMO

BACKGROUND: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. METHODS: We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot." Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI). RESULTS: We observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27). CONCLUSION: We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.

3.
Arthritis Rheumatol ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586363

RESUMO

OBJECTIVES: To assess epicardial adipose tissue volume (EATv) and its link to coronary atherosclerosis and plaque morphology in patients with rheumatoid arthritis (RA) and age- and gender-matched controls. METHODS: Computed tomography angiography evaluated EATv and coronary plaque in 139 RA patients and 139 non-RA controls. All models assessing the effect of EATv on plaque adjusted for age, gender, hypertension, diabetes, dyslipidemia, smoking, family history of coronary artery disease, and obesity (body mass index≥30 kg/m2 ). RESULTS: Mean (±standard deviation [SD]) log-transformed EATv was similar in RA (4.69±0.36) and controls (4.70±0.42). EATv was higher in RA patients with atherosclerosis versus those without (P=0.046). In stratified analyses, EATv associated with number of segments with plaque in RA (rate ratio=1.20 [95%CI 1.01-1.41] per 1-SD increment in EATv) but not controls (P-for-interaction=0.089). Likewise, EATv (per 1-SD increment) related to the presence of multivessel or obstructive disease (odds ratio [OR]=1.63 [95%CI 1.04-2.61]), noncalcified plaque (OR=1.78 [95%CI 1.17-2.70]), and vulnerable plaque (OR=1.77 [95%CI 1.03-3.04]) in RA but not controls (all P-for-interaction≤0.048). Among RA patients, EATv associated with number of segments with plaque in those with RA<10 years, who were cardiovascular risk factor-free, and who were not obese (all P-for-interaction≤0.017). CONCLUSION: Despite similar EATv in RA and controls, EATv associated with greater plaque burden and presence of plaques with a noncalcified component and vulnerability features only in RA. EAT may be more pathogenic in RA and play a role in early-stage atherosclerosis. Its value as a biomarker of subclinical atherosclerosis and cardiovascular risk in RA warrants further studies.

4.
Coron Artery Dis ; Publish Ahead of Print2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33417340

RESUMO

BACKGROUND: Carotid intima-media thickness (CIMT) is regarded as a controversial risk marker for cardiovascular disease (CVD). We aimed to evaluate the role of CIMT and carotid plaque progression as predictors for the progression of coronary plaque and compositions. METHODS: In the Garlic 4 study, asymptomatic patients with intermediate CVD risk (Framingham risk score 6-20%) were recruited for a serial carotid ultrasound, and coronary artery calcium score (CAC)/coronary computed tomography angiography (CCTA) studies for subclinical atherosclerosis at a baseline and 1 year. The association between progression of quantitatively measured coronary plaque compositions and the progression of CIMT/carotid plaque was analyzed. A P value <0.05 is considered as statistically significant. RESULTS: Forty-seven consecutive patients were included. The mean age was 58.5 ± 6.6 years, and 69.1 % were male. New carotid plaque appeared in 34.0 % (n = 16) of participants, and 55.3 % (n = 26) of subjects had coronary plaque progression. In multilinear regression analysis, adjusted by age, gender, and statin use, the development of new carotid plaque was significantly associated with an increase in noncalcified coronary plaque [ß (SE) 2.0 (0.9); P = 0.025] and necrotic core plaque (1.7 (0.6); P = 0.009). In contrast, CIMT progression was not associated with the progression of coronary plaque, or coronary artery calcium (CAC) (P = NS). CONCLUSION: Compared to CIMT, carotid plaque is a better indicator of coronary plaque progression. The appearance of a new carotid plaque is associated with significant progression of necrotic core and noncalcified plaque, which are high-risk coronary plaque components.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33451974

RESUMO

BACKGROUND: The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE). METHODS: The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted. RESULTS: The study population comprised 1166 patients (age 60.5 â€‹± â€‹9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P â€‹< â€‹0.001. CONCLUSIONS: Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33454249

RESUMO

OBJECTIVES: This study aimed to examine the concordance of coronary computed tomographic angiography (CCTA) assessment of coronary anatomy and invasive coronary angiography (ICA) as the reference standard in patients enrolled in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA). BACKGROUND: Performance of CCTA compared with ICA has not been assessed in patients with very high burdens of stress-induced ischemia and a high likelihood of anatomically significant coronary artery disease (CAD). A blinded CCTA was performed after enrollment to exclude patients with left main (LM) disease or no obstructive CAD before randomization to an initial conservative or invasive strategy, the latter guided by ICA and optimal revascularization. METHODS: Rates of concordance were calculated on a per-patient basis in patients randomized to the invasive strategy. Anatomic significance was defined as ≥50% diameter stenosis (DS) for both modalities. Sensitivity analyses using a threshold of ≥70% DS for CCTA or considering only CCTA images of good-to-excellent quality were performed. RESULTS: In 1,728 patients identified by CCTA as having no LM disease ≥50% and at least single-vessel CAD, ICA confirmed 97.1% without LM disease ≥50%, 92.2% with at least single-vessel CAD and no LM disease ≥50%, and only 4.9% without anatomically significant CAD. Results using a ≥70% DS threshold or only CCTA of good-to-excellent quality showed similar overall performance. CONCLUSIONS: CCTA before randomization in ISCHEMIA demonstrated high concordance with subsequent ICA for identification of patients with angiographically significant disease without LM disease.

7.
Coron Artery Dis ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33471470

RESUMO

Chest pain and dyspnea are common presentations for symptomatic individuals with suspected coronary artery disease (CAD) in the primary care office and cardiology clinics. However, it is imperative to properly diagnose who should undergo further evaluation for cardiac etiologies of chest pain, with either noninvasive or invasive imaging tests. The purpose of this review is to highlight the role of coronary artery calcium (CAC) score as a screening tool for symptomatic patients to detect CAD. The purpose of CAC scoring is to establish the presence and severity of coronary atherosclerosis that can play a vital role in symptomatic patients. The use of CAC testing in symptomatic patients has traditionally been limited due to fundamental concerns, including the occurrence of coronary calcification relatively late in the atherosclerotic process and high prevalence of CAC in the population. Further issue relates to its low specificity for obstructive CAD, as well as demonstration of significant ethnic variability in plaque composition and calcification patterns. CAC testing gained attention as an inexpensive, rapid, reproducible and a well-tolerated alternative to exclude CAD in symptomatic patients and defer further invasive imaging tests. This article will review the available literature in regard to the use of CAC in symptomatic populations.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33454260

RESUMO

OBJECTIVES: This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA). BACKGROUND: Coronary CTA can noninvasively assess coronary plaques quantitatively. METHODS: Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome. RESULTS: Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm3 [interquartile range (IQR): 0.0 to 39.6 mm3]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm3 [IQR: 0.0 to 127.4 mm3]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm3 [IQR: 96.7 to 306.4 mm3]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features. CONCLUSIONS: The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

9.
J Diabetes Complications ; 35(3): 107840, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33419635

RESUMO

INTRODUCTION: Coronary artery disease (CAD) is leading cause of morbidity and mortality among type 2 diabetics (T2DM). METHODS: 140 T2DM will be enrolled in randomized, double blind, placebo controlled Semaglutide Treatment On Coronary Plaque Progression (STOP) trial to determine effect of weekly subcutaneous semaglutide on coronary plaque progression. All participants will undergo Coronary Artery Calcium (CAC) Scoring and Coronary Computed Tomography Angiography (CCTA) at our center. A Fisher test, ANOVA and Kruskal Wallis were used. RESULTS: As of May 2020, 87 patients (81%) randomized (mean age 56.4 ± 8.4 yrs. and 62% male) with documented CAD by CCTA. Approximately 20% of screened study population were screen failed due to normal coronaries (n= 14) or HbA1C<7 (n=7). Of interest, 14 persons with diabetes with normal coronaries (no calcification) were significantly more likely to be females (21% vs 62%), have higher glomerular filtration rate (106.5 ± 19.4 vs 89.9 ± 22.6 mL/min/1.73m2; p= 0.006), and younger (53.4 ± 9.0 vs 56.4 ± 8.4 yrs.; p=0.02) than those who were randomized. CONCLUSION: Among T2DM, there is a significant portion who have normal coronary arteries and may have a better prognosis. Excluding these participants from cardiovascular studies may improve power and decrease sample size.

10.
J Clin Lipidol ; 15(1): 33-60, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33419719

RESUMO

An Expert Panel of the National Lipid Association reviewed the evidence related to the use of coronary artery calcium (CAC) scoring in clinical practice for adults seen for primary prevention of atherosclerotic cardiovascular disease. Recommendations for optimal use of this test in adults of various races/ethnicities, ages and multiple domains of primary prevention, including those with a 10-year ASCVD risk <20%, those with diabetes or the metabolic syndrome, and those with severe hypercholesterolemia were provided. Recommendations were also made on optimal timing for repeat calcium scoring after an initial test, use of CAC scoring in those taking statins, and its role in informing the clinician patient discussion on the benefit of aspirin and anti-hypertensive drug therapy. Finally, a vision is provided for the future of coronary calcium scoring.

11.
Int J Cardiol ; 322: 40-42, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871187
12.
Semin Arthritis Rheum ; 51(1): 20-27, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360226

RESUMO

OBJECTIVES: To evaluate whether anti-Beta-2-Glycoprotein-I (anti-ß2GPI) IgA antibodies associate with progression of coronary atherosclerosis and cardiovascular disease (CVD) events in rheumatoid arthritis (RA). METHODS: One hundred-fifty patients underwent plaque evaluation (total, non-calcified, mixed and calcified) with coronary computed tomography angiography; 101 were re-imaged within 6.9±0.3 years to assess progression. The Framingham-D'Agostino score assessed cardiovascular risk. Coronary artery calcium (CAC) and segment involvement score quantified plaque burden. RESULTS: Anti-ß2GPI IgA were seen in 45 (30%) patients. Despite no link to baseline plaque burden, anti-ß2GPI IgA associated with segment involvement score increase (adjusted-RR=1.64 [95%CI 1.02-2.63]), CAC change (adjusted-ß=0.33 [95%CI 0.002-0.656]) and developing new extensive or obstructive plaque at follow-up (adjusted-OR=4.24 [95%CI 1.30-13.87]). Adding anti-ß2GPI IgA to logistic regression models with conventional risk factors predicting plaque progression outcomes increased Area under the receiver-operator curve and improved Net Reclassification and Integrated Discrimination Improvement indices (all P<0.05). In per-segment analyses, anti-ß2GPI IgA predicted mixed plaque formation (adjusted-OR=3.20 [95%CI 1.01-10.09]) and lower likelihood of transition of mixed to calcified plaque (adjusted-OR=0.19 [95%CI 0.04-0.96]). Anti-ß2GPI IgA moderated the effect of C-reactive protein on CAC change such that C-reactive protein associated with CAC change (ß=0.26 [95%CI 0.14-0.38]) and CVD risk (adjusted-HR=1.89 [95%CI 1.02-3.51]) only in anti-ß2GPI IgA positive patients. CONCLUSION: Anti-ß2GPI IgA addition to clinical risk models improved prediction accuracy of CAC, plaque progression and transition to extensive/obstructive disease. They associated with new high-risk mixed plaques and delayed healing to calcified lesions. Anti-ß2GPI IgA further modified the effect of inflammation on plaque progression and CVD events.

13.
14.
Curr Opin Nephrol Hypertens ; 30(1): 38-46, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33186224

RESUMO

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). However, traditional CVD risk prediction equations do not work well in patients with CKD, and inclusion of kidney disease metrics such as albuminuria and estimated glomerular filtration rate have a modest to no benefit in improving prediction. RECENT FINDINGS: As CKD progresses, the strength of traditional CVD risk factors in predicting clinical outcomes weakens. A pooled cohort equation used for CVD risk prediction is a useful tool for guiding clinicians on management of patients with CVD risk, but these equations do not calibrate well in patients with CKD, although a number of studies have developed modifications of the traditional equations to improve risk prediction. The reason for the poor calibration may be related to the fact that as CKD progresses, associations of traditional risk factors such as BMI, lipids and blood pressure with CVD outcomes are attenuated or reverse, and other risk factors may become more important. SUMMARY: Large national cohorts such as the US Veteran cohort with many patients with evolving CKD may be useful resources for the developing CVD prediction models; however, additional considerations are needed for the unique composition of patients receiving care in these healthcare systems, including those with multiple comorbidities, as well as mental health issues, homelessness, posttraumatic stress disorders, frailty, malnutrition and polypharmacy. Machine learning over conventional risk prediction models may be better suited to handle the complexity needed for these CVD prediction models.

15.
Am J Med ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285128

RESUMO

BACKGROUND: The AHA has defined Life's simple 7 (LS7) as a measure of overall Cardiovascular health . Non-alcoholic fatty liver disease (NAFLD) has been concerned as a risk factor for cardiovascular disease .We evaluated the association between LS7 and NAFLD. METHODS: We evaluate participants form The Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Cardiovascular health score was calculated from the Life's simple 7 metrics. A score of 0-8 was considered inadequate, 9-10 average, and 11-14, optimal. NAFLD was defined using non-contrast cardiac CT and a liver/spleen attenuation ratio (L/S) < 1. Multivariable regression were performed to evaluate the association. RESULTS: Our cross-sectional analysis of 3,901 participants showed 19% (n=747) had optimal cardiovascular health, 33% (n=1,270) had average and 48% (n=1,884) had inadequate. White participants were most likely to have an optimal score (51%, n=378) while African American participants had the lowest proportion with optimal scores (16%, n=120; p <0.001). The overall prevalence of NAFLD was 18% with a distribution of 7%, 14%, and 25% in the optimal, average, and inadequate score categories, respectively (p<0.001). Adjusted for risk factors, average and optimal health categories had lower odds of NAFLD compared to those with inadequate scores: odds ratio (OR) for average, 0.44 (95% CI 0.36-0.54); optimal, OR 0.19 (95% CI 0.14-0.26). This association was similar across gender, race and age groups. CONCLUSION: A more favorable cardiovascular health score was associated with a lower prevalence of NAFLD. This study may suggest a potential of Life's simple 7 in the prevention of liver disease.

16.
Am J Cardiol ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278360

RESUMO

Current risk stratification strategies do not fully explain cardiovascular disease (CVD) risk. We aimed to evaluate the association of low-density lipoprotein (LDL-P) and high-density lipoprotein (HDL-P) particles with progression of coronary artery calcium and carotid wall injury. All participants in the Multi-Ethnic Study Atherosclerosis (MESA) with LDL-P and HDL-P measured by ion mobility, coronary artery calcium score (CAC), carotid intima-media thickness (IMT) and carotid plaque data available at Exam 1 and 5 were included in the study. CAC progression was annualized and treated as a categorical or continuous variable. Carotid IMT and plaque progression were treated as continuous variables. Fully adjusted regression models included established CVD risk factors, as well as traditional lipids. Mean (±SD) follow-up duration was 9.6±0.6 years. All LDL-P subclasses as well as large HDL-P at baseline were positively and significantly associated with annualized CAC progression, however, after adjustment for established risk factors and traditional lipids, only the association with medium and very small LDL-P remained significant (ß -0.02, p=0.019 and ß 0.01, p=0.003, per 1 nmol/l increase, respectively). Carotid plaque score progression was positively associated with small and very small LDL-P (p<0.01 for all) and non-HDL-P (p=0.013). Only the association with very small LDL-P remained significant in a fully adjusted model (p=0.035). Mean IMT progression was not associated with any of the lipid particles. In conclusion, in the MESA cohort, LDL-P measured by ion mobility was significantly associated with CAC progression as well as carotid plaque progression beyond the effect of traditional lipids.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33331631

RESUMO

AIMS: Aortic valve calcification (AVC) has been shown to be associated with increased cardiovascular disease (CVD) risk; however, whether this is independent of traditional risk factors and coronary artery calcification (CAC) remains unclear. METHODS AND RESULTS: From the multicentre CAC Consortium database, 10 007 patients (mean 55.8±11.7 years, 64% male) with concomitant CAC and AVC scoring were included in the current analysis. AVC score was quantified using the Agatston score method and categorized as 0, 1-99, and ≥100. The endpoints were all-cause, CVD, and coronary heart disease (CHD) deaths. AVC (AVC>0) was observed in 1397 (14%) patients. During a median 7.8 (interquartile range: 4.7-10.6) years of study follow-up, 511 (5.1%) deaths occurred; 179 (35%) were CVD deaths, and 101 (19.8%) were CHD deaths. A significant interaction between CAC and AVC for mortality was observed (P<0.001). The incidence of mortality events increased with higher AVC; however, AVC ≥100 was not independently associated with all-cause, CVD, and CHD deaths after adjusting for CVD risk factors and CAC (P=0.192, 0.063, and 0.206, respectively). When further stratified by CAC<100 or ≥100, AVC ≥100 was an independent predictor of all-cause and CVD deaths only in patients with CAC <100, after adjusting for CVD risk factors and CAC [hazard ratio (HR): 1.93, 95% confidence interval (CI): 1.14-3.27; P=0.013 and HR: 2.71, 95% CI: 1.15-6.34; P=0.022, respectively]. CONCLUSION: Although the overall prognostic significance of AVC was attenuated after accounting for CAC, high AVC was independently associated with all-cause and CVD deaths in patients with low coronary atherosclerosis burden.

18.
J Am Heart Assoc ; 9(23): e017645, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33222591

RESUMO

Background Hospitalization with community-acquired pneumonia (CAP) is associated with an increased risk of cardiovascular disease (CVD) events in patients uninfected with HIV. We evaluated whether people living with HIV (PLWH) have a higher risk of CVD or mortality than individuals uninfected with HIV following hospitalization with CAP. Methods and Results We analyzed data from the Veterans Aging Cohort Study on US veterans admitted with their first episode of CAP from April 2003 through December 2014. We used Cox regression analyses to determine whether HIV status was associated with incident CVD events and mortality from date of admission through 30 days after discharge (30-day mortality), adjusting for known CVD risk factors. We included 4384 patients (67% [n=2951] PLWH). PLWH admitted with CAP were younger, had less severe CAP, and had fewer CVD risk factors than patients with CAP who were uninfected with HIV. In multivariable-adjusted analyses, CVD risk was similar in PLWH compared with HIV-uninfected (hazard ratio [HR], 0.89; 95% CI, 0.70-1.12), but HIV infection was associated with higher mortality risk (HR, 1.49; 95% CI, 1.16-1.90). In models stratified by HIV status, CAP severity was significantly associated with incident CVD and 30-day mortality in PLWH and patients uninfected with HIV. Conclusions In this study, the risk of CVD events during or after hospitalization for CAP was similar in PLWH and patients uninfected with HIV, after adjusting for known CVD risk factors and CAP severity. HIV infection, however, was associated with increased 30-day mortality after CAP hospitalization in multivariable-adjusted models. PLWH should be included in future studies evaluating mechanisms and prevention of CVD events after CAP.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33231259

RESUMO

CONTEXT: Glycogen storage diseases are rare. Increased glycogen in the liver results in increased attenuation. OBJECTIVE: Investigate the association and function of a noncoding region associated with liver attenuation but not histologic nonalcoholic fatty liver disease. DESIGN: Genetics of Obesity-associated Liver Disease Consortium. SETTING: Population-based Main Outcome: Computed tomography measured liver attenuation. RESULTS: Carriers of rs4841132-A (frequency 2-19%) do not show increased hepatic steatosis; they have increased liver attenuation indicative of increased glycogen deposition. rs4841132 falls in a noncoding RNA LOC157273 ~190kb upstream of PPP1R3B. We demonstrate that rs4841132-A increases PPP1R3B through a cis genetic effect. Using CRISPR/Cas9 we engineered a 105bp deletion including rs4841132-A in human hepatocarcinoma cells which increases PPP1R3B, decreases LOC157273 and increases glycogen perfectly mirroring the human disease. Overexpression of PPP1R3B or knockdown of LOC157273 increased glycogen but did not result in decreased LOC157273 or increased PPP1R3B, respectively, suggesting that the effects may not all occur via affecting RNA levels. Based on EHR data, rs4841132-A associates with all components of the metabolic syndrome (MetS). However, rs4841132-A associated with decreased low-density lipoprotein (LDL) cholesterol and risk for myocardial infarction (MI). A metabolic signature for rs4841132-A includes increased glycine, lactate, triglycerides and decreased acetoacetate and beta-hydroxybutyrate. CONCLUSIONS: These results show that rs4841132-A promotes a hepatic glycogen storage disease by increasing PPP1R3B and decreasing LOC157273. rs4841132-A promotes glycogen accumulation and development of MetS but lowers LDL cholesterol and risk for MI. These results suggest that elevated hepatic glycogen is one cause of MetS that does not invariably promote MI.

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