Publications by authors named "Mohamed B Elshazly"

39 Publications

Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study.

Eur Heart J 2021 Jul 19. Epub 2021 Jul 19.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA.

Aims: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.

Methods And Results: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.35). Similar results were shown when examining discordance across clinical cutpoints.

Conclusions: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.
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http://dx.doi.org/10.1093/eurheartj/ehab432DOI Listing
July 2021

Kidney Transplant Recipients Infected With Coronavirus Disease 2019: Retrospective Qatar Experience.

Transplant Proc 2021 Jun 11. Epub 2021 Jun 11.

Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar; Weill Cornell Medical College, Doha, Qatar. Electronic address:

Background: This study aimed to evaluate the incidence of coronavirus disease 2019 (COVID-19) infection on kidney transplant, mortality, and risk factors associated with infection acquisition and severe illness in kidney transplant recipients with COVID-19.

Methods: Of 693 kidney transplant recipients who reported to our center, 249 were tested for COVID-19 by throat and nasal swab reverse transcription polymerase chain reaction. Of these, 43 recipients tested positive and 206 recipients tested negative. Among the 43 positive recipients, 9 were treated within an isolation facility, 25 were admitted to the hospital, and 9 were admitted to the intensive care unit (ICU). Risk factors associated with positive results and ICU admission were evaluated.

Results: COVID-19 was found in 6% of transplant recipients. Asian ethnicity (p = .003), history of hypertensive nephropathy (p = .01), AB blood group (P = .04), and higher tacrolimus trough levels (P = .007) were more frequent in the COVID-19 positive than in the COVID-19 negative group. ICU admission was more frequent in recipients presenting with fever, shortness of breath, and acute allograft dysfunction. Renal replacement therapy was required in 3 (7%) of 43 recipients, and mortality was reported in 1 (2.3%) recipient. Acute allograft dysfunction was an independent risk factor for severe COVID-19 (odds ratio, 93.7; 95% confidence interval, 2.37-3710.94; P = .02).

Conclusions: Higher tacrolimus targets may be associated with COVID-19 development. Acute kidney injury during the COVID-19 course may be a sign of severe disease. Prognostication of COVID-19 severity in kidney transplant recipients is crucial for early recognition of critical illness and may ensure early intervention.
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http://dx.doi.org/10.1016/j.transproceed.2021.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193030PMC
June 2021

New Antidiabetes Medications and Their Cardiovascular and Renal Benefits.

Cardiol Clin 2021 Aug;39(3):335-351

Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Electronic address:

After 12 years of rigorous cardiovascular outcome trials (CVOTs), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) emerged as new therapeutic options for patients with type 2 diabetes mellitus to reduce the risk of heart disease. SGLT2i additionally cause a reduction in heart failure and renal events in patients both with and without diabetes. This article reviews the major CVOTs that support the use of these agents, describes the mechanisms of action that lead to their broad cardiorenal benefits, explains current guidelines, and offers practical clinical advice to initiate and monitor treatment with these agents.
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http://dx.doi.org/10.1016/j.ccl.2021.04.007DOI Listing
August 2021

Atrial fibrillation catheter ablation complications in obese and diabetic patients: Insights from the US Nationwide Inpatient Sample 2005-2013.

Clin Cardiol 2021 Aug 15;44(8):1151-1160. Epub 2021 Jun 15.

Research Department, Weill Cornell Medicine-Qatar, Doha, Qatar.

Background: Obesity and diabetes are risk factors for atrial fibrillation (AF) incidence and recurrence after catheter ablation. However, their impact on post-ablation complications in real-world practice is unknown.

Objectives: We examine annual trends in AF ablations and procedural outcomes in obese and diabetic patients in the US and whether obesity and diabetes are independently associated with adverse outcomes.

Methods: Using the Nationwide Inpatient Sample (2005-2013), we identified obese and diabetic patients admitted for AF ablation. Common complications were identified using ICD-9-CM codes. The primary outcome included the composite of any in-hospital complication or death. Annual trends of the primary outcome, length-of-stay (LOS) and total-inflation adjusted hospital charges were examined. Multivariate analyses studied the association of obesity and diabetes with outcomes.

Results: An estimated 106 462 AF ablations were performed in the US from 2005 to 2013. Annual trends revealed a gradual increase in ablations performed in obese and diabetic patients and in complication rates. The overall rate of the primary outcome in obese was 11.7% versus 8.2% in non-obese and 10.7% in diabetic versus 8.2% in non-diabetic patients (p < .001).

Conclusions: Obesity was independently associated with increased complications (adjusted OR, 95% CI:1.39, 1.20-1.62), longer LOS (1.36, 1.23-1.49), and higher charges (1.16, 1.12-1.19). Diabetes was only associated with longer LOS (1.27, 1.16-1.38). Obesity, but not diabetes, in patients undergoing AF ablation is an independent risk factor for immediate post-ablation complications and higher costs. Future studies should investigate whether weight loss prior to ablation reduces complications and costs.
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http://dx.doi.org/10.1002/clc.23667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364717PMC
August 2021

Systemic inflammation may induce cardiac injury in COVID-19 patients including children and adolescents without underlying cardiovascular diseases: A systematic review.

Cardiovasc Revasc Med 2021 Apr 15. Epub 2021 Apr 15.

Weill Cornell Medicine Qatar, Qatar Foundation, Education City, Al, Luqta St. Ar-Rayyan, P.O. Box 24144, Doha, Qatar. Electronic address:

Coronavirus disease 2019(COVID-19) is an ongoing global pandemic with a daily increasing number of affected individuals and a relatively high mortality rate. COVID-19 patients that develop cardiac injury are at increased risk of a worse clinical course with higher rates of mortality. Increasing amounts of evidence suggest that a system-wide inflammatory response and a cytokine storm mediated type syndrome plays a crucial role in disease progression. This systematic review investigates the possible role of hyperinflammation in inducing cardiac injury as one of the severe complications of COVID-19. A systematic literature search was performed using PubMed, Embase and Scopus databases to identify relevant clinical studies that investigated cardiovascular injury manifestations and reported inflammatory and cardiac biomarkers in COVID-19 patients. Only 29 studies met our inclusion criteria and the majority of these studies demonstrated significantly elevated inflammatory and cardiac blood markers. It was evident that underlying cardiovascular diseases may increase the risk of developing cardiac injury. However, many COVID-19 patients included in this review, developed different types of cardiac injury without having any underlying cardiovascular diseases. Furthermore, many of these patients were either children or adolescents. Therefore, age and comorbidities may not always be the two main risk factors that dictate the severity and outcome of COVID-19. Further investigations are required to understand the underlying mechanisms of pathogenicity as an urgent requirement to develop the appropriate treatment and prevention strategies. These strategies may specifically target hyperinflammation as a suspected driving factor for some of the severe complications of COVID-19.
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http://dx.doi.org/10.1016/j.carrev.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046745PMC
April 2021

LDL-C-lowering therapies reduce major vascular events in patients aged ≥75 y.

Ann Intern Med 2021 04 6;174(4):JC38. Epub 2021 Apr 6.

Weill Cornell Medicine-Qatar, Doha, Qatar (I.Y.E., M.B.E.).

Source Citation: Gencer B, Marston NA, Im K, et al. Lancet. 2020;396:1637-43. 33186535.
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http://dx.doi.org/10.7326/ACPJ202104200-038DOI Listing
April 2021

Smart wearable devices in cardiovascular care: where we are and how to move forward.

Nat Rev Cardiol 2021 08 4;18(8):581-599. Epub 2021 Mar 4.

Department of Medical Education, Weill Cornell Medicine, Doha, Qatar.

Technological innovations reach deeply into our daily lives and an emerging trend supports the use of commercial smart wearable devices to manage health. In the era of remote, decentralized and increasingly personalized patient care, catalysed by the COVID-19 pandemic, the cardiovascular community must familiarize itself with the wearable technologies on the market and their wide range of clinical applications. In this Review, we highlight the basic engineering principles of common wearable sensors and where they can be error-prone. We also examine the role of these devices in the remote screening and diagnosis of common cardiovascular diseases, such as arrhythmias, and in the management of patients with established cardiovascular conditions, for example, heart failure. To date, challenges such as device accuracy, clinical validity, a lack of standardized regulatory policies and concerns for patient privacy are still hindering the widespread adoption of smart wearable technologies in clinical practice. We present several recommendations to navigate these challenges and propose a simple and practical 'ABCD' guide for clinicians, personalized to their specific practice needs, to accelerate the integration of these devices into the clinical workflow for optimal patient care.
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http://dx.doi.org/10.1038/s41569-021-00522-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931503PMC
August 2021

The Interplay Between the Immune System, the Renin-Angiotensin-Aldosterone System (RAAS), and RAAS Inhibitors May Modulate the Outcome of COVID-19: A Systematic Review.

J Clin Pharmacol 2021 08 7;61(8):987-1000. Epub 2021 Apr 7.

Weill Cornell Medicine Qatar, Qatar Foundation, Education City, Doha, Qatar.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), numerous research has been undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS-CoV-2 invasion mechanism and the renin-angiotensin-aldosterone system (RAAS) receptors, created many debates about the possible consequences of using RAAS-modulating drugs including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of coronavirus disease 2019 (COVID-19) in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. Although several studies mainly analyzed the outcomes of the disease, this review aimed to compare specific blood markers in both groups of COVID-19 patients to gain better insight into the interaction of ACEi/ARBs with different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID-19 patients who used or did not use ACEi/ARBs. Interestingly, 6 studies reported lower inflammatory markers in COVID-19 patients who used ACEi/ARBs, and 6 studies reported better outcomes among the same group. We therefore concluded that the use of ACEi/ARBs may not lead to worse prognosis of COVID-19 and may even play a protective role against the hyperinflammatory response associated with COVID-19.
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http://dx.doi.org/10.1002/jcph.1852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014479PMC
August 2021

Exercise Ventricular Rates, Cardiopulmonary Exercise Performance, and Mortality in Patients With Heart Failure With Atrial Fibrillation.

Circ Heart Fail 2021 02 22;14(2):e007451. Epub 2021 Jan 22.

Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic (M.B.E., B.L.W., K.T., Y.W., E.D., W.J., O.W., L.C.).

Background: In heart failure (HF) with sinus rhythm, resting and exercise heart rates correlate with exercise capacity and mortality. However, in HF with atrial fibrillation (AF), this correlation is unknown. Our aim is to investigate the association of resting and exercise ventricular rates (VRs) with exercise capacity and mortality in HF with AF.

Methods: We identified 903 patients with HF and AF referred for cardiopulmonary stress testing. AF was defined as history of AF and AF during cardiopulmonary stress testing. We constructed multivariable models to evaluate the association of resting VR, peak exercise VR, VR reserve (peak VR-resting VR), and chronotropic index with (1) peak oxygen consumption (PVO) ≤18 mL/kg per minute, (2) continuous PVO, and (3) 10-year all-cause mortality.

Results: Median (25th-75th percentile) age was 60 (52-67) years, left ventricular ejection fraction was 25 (15-50)%, and 76.1% were males. Patients with lower (quartile 1) compared with higher (quartile 4) peak VR, VR reserve, and chronotropic index were more likely to have PVO ≤18 mL/kg per min (adjusted odds ratio [95% CI]: 14.92 [8.07-27.58], 24.60 [12.36-48.98], and 22.31 [11.24-44.27], respectively), and higher all-cause mortality (adjusted hazard ratio [95% CI]: 2.56 [1.62-4.04], 2.29 [1.47-3.59], and 2.30 [1.51-3.49], respectively). For every 10 beats per minute increase in VR reserve, PVO increased by 1.05 mL/kg per minute (B-coefficient [95% CI]: 1.05 [0.94-1.15]) and mortality decreased by 12% (adjusted hazard ratio [95% CI]: 0.88 [0.83-0.94]). Resting VR was associated with PVO (B-coefficient [95% CI]: -0.46 [-0.70 to -0.23]) but not mortality (adjusted hazard ratio [95% CI]: 0.97 [0.88-1.06]).

Conclusions: In patients with HF and AF, higher resting VR and lower peak exercise VR, VR reserve, and chronotropic index were all associated with worse peak exercise capacity, but only lower exercise VR parameters were associated with higher mortality. Dedicated studies are needed to gauge whether modulating exercise VR enhances exercise performance and outcomes.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007451DOI Listing
February 2021

Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

Europace 2021 07;23(7):1063-1071

Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.

Aims: Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation.

Methods And Results: We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001).

Conclusion: Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.
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http://dx.doi.org/10.1093/europace/euaa419DOI Listing
July 2021

New Decade, New FDA Guidance for Diabetes Drug Development: Lessons Learned and Future Directions.

J Am Coll Cardiol 2020 11;76(21):2522-2526

Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Cardiology, Department of Medicine, Weill Cornell Medical College-Qatar, Education City, Doha, Qatar. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2020.09.590DOI Listing
November 2020

Impact of Nonalcoholic Fatty Liver Disease on Arrhythmia Recurrence Following Atrial Fibrillation Ablation.

JACC Clin Electrophysiol 2020 10 12;6(10):1278-1287. Epub 2020 Aug 12.

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Objectives: This study sought to investigate the association between nonalcoholic fatty liver disease (NAFLD) and arrhythmia recurrence following atrial fibrillation ablation; and to examine the impact of NAFLD stage on outcomes.

Background: Metabolic derangements, including obesity and diabetes, are associated with incident and recurrent atrial fibrillation (AF), in addition to the development of NAFLD.

Methods: This was a retrospective study of 267 consecutive patients undergoing AF ablation, 89 of whom were diagnosed with NAFLD prior to ablation and matched in a 2:1 manner based on age, sex, body mass index, ejection fraction, and AF type with 178 patients without NAFLD. Patients were monitored for arrhythmia recurrence during a mean follow-up of 29 months.

Results: Recurrent arrhythmia was observed in 50 (56%) patients with NAFLD compared with 37 (21%) without NAFLD. Epicardial fat volume was measured on computed tomography and was significantly higher among those with NAFLD (248 ± 125 ml vs. 223 ± 97 ml; p = 0.01). On multivariable models adjusting for sleep apnea, body mass index, heart failure, AF type, and left atrial size, NAFLD was independently associated with increased rates of arrhythmia recurrence (hazard ratio: 3.010; 95% confidence interval: 1.980 to 4.680; p < 0.0001).

Conclusions: NAFLD is associated with significantly increased arrhythmia recurrence rates following AF ablation. Identification and reversal, where possible, may result in improved arrhythmia-free survival.
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http://dx.doi.org/10.1016/j.jacep.2020.05.023DOI Listing
October 2020

Accuracy of New Equation to Calculate Low-Density Lipoprotein Cholesterol.

JAMA Cardiol 2021 Jan;6(1):121-122

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1001/jamacardio.2020.4411DOI Listing
January 2021

Atrial Fibrillation in Transthyretin Cardiac Amyloidosis: Predictors, Prevalence, and Efficacy of Rhythm Control Strategies.

JACC Clin Electrophysiol 2020 09 29;6(9):1118-1127. Epub 2020 Jul 29.

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Objectives: This study sought to determine the incidence and prevalence of atrial fibrillation (AF) in transthyretin cardiac amyloidosis (ATTR-CA); to study the factors associated with the development of AF in this population; to study the prognostic implications of AF and maintenance of normal sinus rhythm (NSR) in patients with ATTR-CA; and to determine the impact of ATTR-CA stage on AF prevalence, outcomes, and efficacy of rhythm control strategies.

Background: AF is common in patients with ATTR-CA. The aim of this study was to determine the predictors, prevalence, and outcomes of AF in patients with ATTR-CA in addition to the efficacy of rhythm control strategies.

Methods: This was a retrospective cohort study of 382 patients with ATTR-CA diagnosed at our institution between January 2004 and January 2018. Means testing, and univariable and multivariable models were used.

Results: AF occurred in 265 (69%) patients. Factors associated with the development of AF included older age, advanced ATTR-CA stage, and higher left atrial volume index. Antiarrhythmic therapy (AAT) was used in 35% of patients with AF; cardioversion was performed in 45%, and 5% underwent AF ablation. Rhythm control strategies were substantially more effective when performed earlier in the disease course. During a mean follow-up of 35 months, no difference in mortality between patients with AF and those without AF was observed (65% vs. 49%; p = 0.76). On Cox proportional hazards analyses, maintenance of normal sinus rhythm and tafamidis use were associated with improved survival, whereas advanced ATTR-CA stage and higher New York Heart Association functional class were associated with increased mortality.

Conclusions: With advancing ATTR-CA stage, AF became more prevalent, occurring in 69% of our entire study cohort. Rhythm control strategies including AAT, direct-current cardioversion, and AF ablation were substantially more effective when performed earlier during the disease course.
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http://dx.doi.org/10.1016/j.jacep.2020.04.019DOI Listing
September 2020

Role of Coronary Artery and Thoracic Aortic Calcium as Risk Modifiers to Guide Antihypertensive Therapy in Stage 1 Hypertension (From the Multiethnic Study of Atherosclerosis).

Am J Cardiol 2020 07 14;126:45-55. Epub 2020 Mar 14.

National Institute for Prevention and Cardiovascular Health, National University of Ireland, Ireland.

The 2017 American blood pressure (BP) guidelines recommended a personalized risk-based approach to treatment in stage 1 hypertension. We sought to establish the utility of coronary artery or thoracic aortic calcium (CAC or TAC) as additional risk modifiers in this setting. We included 1859 Multiethnic Study of Atherosclerosis participants with stage 1 hypertension. We compared adjusted HR for the composite outcome of incident atherosclerotic cardiovascular disease or heart failure across predefined categories of either CAC or TAC (0, 1 to 100, or >100) in: (1) the full sample; (2) 4 high-risk subgroups recommended for pharmacotherapy to a BP goal <130/80 mm Hg, and (3) low-risk subgroup not eligible for pharmacotherapy. We also estimated the 10-year number-needed-to-treat (NNT) to a systolic BP <130 mm Hg as extrapolated from meta-analyses. Mean age was 62.8 ± 9.4 years, 46% were female and there were 300 events over a median follow-up of 13.8 years. The absolute event rate was 4.1 to 10.8 per 1,000 person-years among high-risk participants with CAC = 0, but 28.4 among low-risk participants with CAC >100. CAC >100 was independently associated with a higher relative risk of events compared with CAC = 0 (e.g., adjusted HR [9.5 (1.8 to 18.7)] in the low-risk subgroup). NNT for CAC = 0 were 3 to 5 times higher than those for CAC >100 in all analyses. TAC was not a reliable risk modifier in our study. In conclusion, CAC, but not TAC, can further guide risk-based allocation of treatment in stage 1 hypertension and should be considered as a risk modifier in future guidelines.
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http://dx.doi.org/10.1016/j.amjcard.2020.02.036DOI Listing
July 2020

Atrial fibrillation ablation in patients with transthyretin cardiac amyloidosis.

Europace 2020 02;22(2):259-264

Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Aims: Atrial fibrillation (AF) occurs in as many as 70% of patients with transthyretin cardiac amyloidosis (ATTR CA). The aim of our study was to investigate the impact of AF ablation on freedom from recurrent arrhythmia, hospitalization for AF or heart failure (HF), and mortality.

Methods And Results: This was a retrospective observational cohort study of 72 patients with ATTR CA and AF, of whom 24 underwent AF ablation and were matched in a 2:1 manner based on age, gender, ATTR CA stage, New York Heart Association functional class, ejection fraction, and date of AF diagnosis with 48 patients with ATTR CA and AF undergoing medical management. During a mean follow-up of 39 ± 26 months, 10 (42%) patients remained free of recurrent arrhythmia following ablation. Ablation was significantly more effective in those with Stage I or II ATTR CA, with 9/14 (64%) patients with Stage I or II ATTR CA remaining free of recurrent arrhythmia compared to only 1/10 (10%) patients with Stage III disease (P = 0.005). Death occurred in 7 (29%) patients in the ablation group compared to 36 (75%) in the non-ablation arm (P = 0.01). Rates of ischaemic stroke were similar in both groups. Ablation was associated with a significant reduction in the frequency of hospitalization for HF/arrhythmia (1.7 ± 2.4 hospitalizations vs. 4 ± 3.5, P = 0.005). On Cox proportional hazards analyses, ablation was associated with improved survival (hazard ratio 0.38, 95% confidence intervals 0.17-0.86; P = 0.02).

Conclusion: Atrial fibrillation ablation is associated with reduced mortality in ATTR CA and is most effective when performed earlier during the disease process.
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http://dx.doi.org/10.1093/europace/euz314DOI Listing
February 2020

High-Sensitivity C-Reactive Protein Discordance With Atherogenic Lipid Measures and Incidence of Atherosclerotic Cardiovascular Disease in Primary Prevention: The ARIC Study.

J Am Heart Assoc 2020 02 30;9(3):e013600. Epub 2020 Jan 30.

Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins School of Medicine Baltimore MD.

Background Inflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high-sensitivity C-reactive protein) is prognostic across various levels of atherogenic lipid measures such as low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high-density lipoprotein cholesterol in primary prevention is unknown. Methods and Results We studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996-1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low-density lipoprotein cholesterol + non-high-density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high-density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow-up of 18.4 (12.8-19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09-1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18-1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (≥7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use. Conclusions Our findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.
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http://dx.doi.org/10.1161/JAHA.119.013600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033866PMC
February 2020

Remnant cholesterol, coronary atheroma progression and clinical events in statin-treated patients with coronary artery disease.

Eur J Prev Cardiol 2020 07 19;27(10):1091-1100. Epub 2019 Nov 19.

Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland Clinic, USA.

Aim: Remnant cholesterol has been proposed to promote atherosclerotic cardiovascular disease independent of low-density lipoprotein cholesterol, yet the underlying mechanisms are not well understood. We aimed to study the association of remnant cholesterol with coronary atheroma progression and clinical events.

Methods: We analyzed data from 5754 patients with coronary artery disease undergoing serial intravascular ultrasonography who were enrolled in 10 trials examining various medical therapies. Remnant cholesterol was calculated as (non-high-density lipoprotein cholesterol - low-density lipoprotein cholesterol (estimated using the Hopkins-Martin equation)). Changes in percentage atheroma volume and 2-year major adverse cardiovascular events were compared across various levels of remnant cholesterol, and multivariable models were used to assess the independent relationship of remnant cholesterol with changes in percentage atheroma volume.

Results: The mean age was 58.1 ± 9.2 years, 28% were women and 96% received a statin. Percentage atheroma volume progression (changes in percentage atheroma volume > 0) occurred in a linear fashion at on-treatment remnant cholesterol levels of 25 mg/dL or greater. The highest on-treatment remnant cholesterol quartile demonstrated greater percentage atheroma volume progression (+0.53 ± 0.26 vs. -0.15 ± 0.25%,  < 0.001) and 2-year major adverse cardiovascular events (23% vs. 14%, log-rank  < 0.001) compared with the lowest. In multivariable analyses, changes in percentage atheroma volume significantly correlated with on-treatment remnant cholesterol ( < 0.001] independent of low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, high-density lipoprotein cholesterol levels and clinical risk factors. Changes in percentage atheroma volume also significantly correlated with changes in remnant cholesterol following multivariable adjustment.

Conclusions: In statin-treated patients with atherosclerotic cardiovascular disease, remnant cholesterol was associated with coronary atheroma progression regardless of conventional lipid parameters, C-reactive protein or clinical risk factors. Higher remnant cholesterol levels also correlated with higher major adverse cardiovascular events. These data support further investigations into remnant cholesterol-lowering interventions in statin-treated patients harboring residual atherosclerotic cardiovascular disease risk.
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http://dx.doi.org/10.1177/2047487319887578DOI Listing
July 2020

Association between pre-ablation bariatric surgery and atrial fibrillation recurrence in morbidly obese patients undergoing atrial fibrillation ablation.

Europace 2019 Oct;21(10):1476-1483

Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave J2-2, Cleveland, OH, USA.

Aims: Obesity decreases arrhythmia-free survival after atrial fibrillation (AF) ablation by mechanisms that are not fully understood. We investigated the impact of pre-ablation bariatric surgery (BS) on AF recurrence after ablation.

Methods And Results: In this retrospective observational cohort study, 239 consecutive morbidly obese patients (body mass index ≥40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were followed for a mean of 22 months prior to ablation. Of these patients, 51 had BS prior to ablation, and our primary outcome was whether BS was associated with a lower rate of AF recurrence during follow-up. Adjustment for confounding was performed with multivariable Cox proportional hazard models and propensity-score based analyses. During a mean follow-up of 36 months after ablation, 10/51 patients (20%) in the BS group had recurrent AF compared with 114/188 (61%) in the non-BS group (P < 0.0001). In the BS group, 6 patients (12%) underwent repeat ablation compared with 77 patients (41%) in the non-BS group, (P < 0.0001). On multivariable analysis, the association between BS and lower AF recurrence remained significant. Similarly, after weighting and adjusting for the inverse probability of the propensity score, BS was still associated with a lower hazard of AF recurrence (hazard ratio 0.14, 95% confidence interval 0.05-0.39; P = 0.002).

Conclusion: Bariatric surgery is associated with a lower AF recurrence after ablation. Morbidly obese patients should be considered for BS prior to AF ablation, though prospective multicentre studies should be performed to confirm our novel finding.
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http://dx.doi.org/10.1093/europace/euz183DOI Listing
October 2019

Total cholesterol/HDL-cholesterol ratio discordance with LDL-cholesterol and non-HDL-cholesterol and incidence of atherosclerotic cardiovascular disease in primary prevention: The ARIC study.

Eur J Prev Cardiol 2020 10 10;27(15):1597-1605. Epub 2019 Jul 10.

Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, USA.

Aims: The total cholesterol (TC)/high-density lipoprotein (HDL) cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures. Analysis of discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease. We aimed to investigate the role of the TC/HDL-cholesterol ratio in determining atherosclerotic cardiovascular disease risk when discordant with low-density lipoprotein (LDL) cholesterol and non-HDL-cholesterol.

Methods: We studied 14,403 Atherosclerosis Risk in Communities (ARIC) study participants who were free of atherosclerotic cardiovascular disease at baseline. TC/HDL-cholesterol discordance with LDL-cholesterol (estimated by the novel Martin/Hopkins method) and non-HDL-cholesterol was assessed at five visits and determined by being at or above the median for each lipid parameter. We constructed Cox proportional hazard models to estimate the risk for incident atherosclerotic cardiovascular disease events associated with each lipid concordance/discordance category using a time-varying approach.

Results: Mean age of participants was 54.1 years, 56% women and 25% black. There were 2634 atherosclerotic cardiovascular disease events over a median (interquartile range) follow-up of 24.2 (16.0-25.4) years. Among individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, 26% and 21% had discordant TC/HDL-cholesterol at or above the median, respectively. These individuals had a 24% (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09, 1.41) and 29% (HR 1.29, 95% CI 1.13, 1.46) greater risk of incident atherosclerotic cardiovascular disease, respectively, compared to those with TC/HDL-cholesterol less than the median after multivariable adjustment. In individuals with diabetes with LDL-cholesterol or non-HDL-cholesterol less than the median, discordant TC/HDL-cholesterol at or above the median was more prevalent at 48% and 38%, respectively.

Conclusion: Clinically significant discordance exists between TC/HDL-cholesterol, available from the standard lipid profile, and the routinely used non-HDL-cholesterol and LDL-cholesterol. Such discordance may help inform atherosclerotic cardiovascular disease risk management, particularly in individuals with diabetes in whom discordance is more common.
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http://dx.doi.org/10.1177/2047487319862401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952589PMC
October 2020

Visit-to-Visit Blood Pressure Variability, Coronary Atheroma Progression, and Clinical Outcomes.

JAMA Cardiol 2019 05;4(5):437-443

Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland, Ohio.

Importance: Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events, but mechanisms and therapeutic implications underlying this association are not well understood.

Objective: To examine the association of intraindividual BPV, coronary atheroma progression, and clinical outcomes using serial intravascular ultrasonography.

Design, Setting, And Participants: Post hoc patient-level analysis of 7 randomized clinical trials conducted from 2004 to 2016 involving 3912 patients in multicenter, international, clinic-based primary and tertiary care centers. Adult patients with coronary artery disease who underwent serial intravascular ultrasonography in the setting of a range of medical therapies were included. Data were analyzed between November 2017 and March 2019.

Exposures: Visit-to-visit BPV measured using intraindividual standard deviation over 3, 6, 12, 18, and 24 months.

Main Outcomes And Measures: Percent atheroma volume (PAV) progression and major adverse cardiovascular events (defined as death, myocardial infarction, stroke, urgent revascularization for acute coronary syndrome, and hospitalization for unstable angina).

Results: Of 3912 patients, the mean (SD) age was 58 (9) years, 1093 (28%) were women, and 3633 (93%) were white . Continuous change in PAV was significantly associated with systolic BPV (β, .049; 95% CI, 0.021-0.078; P = .001), diastolic BPV (β, .031; 95% CI, 0.002-0.059; P = .03), and pulse pressure variability (β, .036; 95% CI, 0.006-0.067; P = .02), without a signal for differential effect greater than or less than a mean BP of 140/90 mm Hg. The PAV progression as a binary outcome was significantly associated with systolic BPV (odds ratio, 1.09; 95% CI, 1.01-1.17; P = .02) but not diastolic BPV (odds ratio, 1.04; 95% CI, 0.97-1.11; P = .30) or pulse pressure variability (odds ratio, 1.03; 95% CI, 0.96-1.10; P = .47). Survival curves revealed a significant stepwise association between cumulative major adverse cardiovascular events and increasing quartiles of systolic BPV (Kaplan-Meier estimates for quartiles 1-4: 6.1% vs 8.5% vs 10.1% vs 12.0%, respectively; log-rank P <.001). These distinct stepwise associations were not seen with diastolic BPV or pulse pressure variability.

Conclusions And Relevance: Greater BPV, particularly systolic BPV, is significantly associated with coronary atheroma progression and adverse clinical outcomes. These data suggest maintaining stable blood pressure levels may be important to further improve outcomes in patients with coronary disease.
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http://dx.doi.org/10.1001/jamacardio.2019.0751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537804PMC
May 2019

Reimplantation After Lead Removal.

Card Electrophysiol Clin 2018 12 5;10(4):667-674. Epub 2018 Oct 5.

Department of Cardiac Electrophysiology and Pacing, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue J2-2, Cleveland, OH 44195, USA. Electronic address:

The number of implanted cardiovascular implantable electronic devices (CIEDs) has increased significantly in the last 30 years, which has led to an upsurge in CIED complications, such as infection and lead malfunction requiring CIED extraction. The decision-making process of CIED reimplantation requires meticulous planning that includes careful consideration of several aspects: the reason for extraction, the indication for CIED reimplantation, patients' wishes, timing of reimplantation, the need for a bridging device, and the type and location of device to be reimplanted. In this article, the authors review this decision-making process and the necessary steps to achieve optimal patient outcomes.
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http://dx.doi.org/10.1016/j.ccep.2018.04.004DOI Listing
December 2018

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

Eur Heart J 2018 07;39(27):2551-2558

Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Aims: Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes.

Methods And Results: We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P < 0.01 for all lipoproteins except HDL-C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P < 0.001); non-HDL-C: 1.32 (1.21, 1.45; P < 0.001); TC/HDL-C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)].

Conclusion: Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.
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http://dx.doi.org/10.1093/eurheartj/ehy209DOI Listing
July 2018

Impact of Novel Low-Density Lipoprotein-Cholesterol Assessment on the Utility of Secondary Non-High-Density Lipoprotein-C and Apolipoprotein B Targets in Selected Worldwide Dyslipidemia Guidelines.

Circulation 2018 07 5;138(3):244-254. Epub 2018 Mar 5.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD (V.S., R.Q., E.D.M., P.P.T., S.P.W., R.S.B., S.R.J., S.S.M.).

Background: Selected dyslipidemia guidelines recommend non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as secondary targets to the primary target of low-density lipoprotein-cholesterol (LDL-C). After considering 2 LDL-C estimates that differ in accuracy, we examined: (1) how frequently non-HDL-C guideline targets could change management; and (2) the utility of apoB targets after meeting LDL-C and non-HDL-C targets.

Methods: We analyzed 2518 adults representative of the US population from the 2011 to 2012 National Health and Nutrition Examination Survey and 126 092 patients from the Very Large Database of Lipids study with apoB. We identified all individuals as well as those with high-risk clinical features, including coronary artery disease, diabetes mellitus, and metabolic syndrome who met very high- and high-risk guideline targets of LDL-C <70 and <100 mg/dL using Friedewald estimation (LDL-C) and a novel, more accurate method (LDL-C). Next, we examined those not meeting non-HDL-C (<100, <130 mg/dL) and apoB (<80, <100 mg/dL) guideline targets. In those meeting dual LDL-C and non-HDL-C targets (<70 and <100 mg/dL, respectively, or <100 and <130 mg/dL, respectively), we determined the proportion of individuals who did not meet guideline apoB targets (<80 or <100 mg/dL).

Results: A total of 7% to 9% and 31% to 36% of individuals had LDL-C <70 and <100 mg/dL, respectively. Among those with LDL-C<70 mg/dL, 14% to 15% had non-HDL-C ≥100 mg/dL, and 7% to 8% had apoB ≥80 mg/dL. Among those with LDL-C<100 mg/dL, 8% to 10% had non-HDL-C ≥130 mg/dL and 2% to 3% had apoB ≥100 mg/dL. In comparison, among those with LDL-C<70 or 100 mg/dL, only ≈2% and ≈1% of individuals, respectively, had non-HDL-C and apoB values above guideline targets. Similar trends were upheld among those with high-risk clinical features: ≈0% to 3% of individuals with LDL-C<70 mg/dL had non-HDL-C ≥100 mg/dL or apoB ≥80 mg/dL compared with 13% to 38% and 9% to 25%, respectively, in those with LDL-C<70 mg/dL. With LDL-C or LDL-C<70 mg/dL and non-HDL-C <100 mg/dL, 0% to 1% had apoB ≥80 mg/dL. Among all dual LDL-C or LDL-C<100 mg/dL and non-HDL-C <130 mg/dL individuals, 0% to 0.4% had apoB ≥100 mg/dL. These findings were robust to sex, fasting status, and lipid-lowering therapy status.

Conclusions: After more accurately estimating LDL-C, guideline-suggested non-HDL-C targets could alter management in only a small fraction of individuals, including those with coronary artery disease and other high-risk clinical features. Furthermore, current guideline-suggested apoB targets provide modest utility after meeting cholesterol targets.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01698489.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032463DOI Listing
July 2018

Impact of Atrial Fibrillation on Exercise Capacity and Mortality in Heart Failure With Preserved Ejection Fraction: Insights From Cardiopulmonary Stress Testing.

J Am Heart Assoc 2017 Oct 31;6(11). Epub 2017 Oct 31.

Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH

Background: Atrial fibrillation (AF) has been objectively associated with exercise intolerance in patients with heart failure with reduced ejection fraction; however, its impact in patients with heart failure with preserved ejection fraction has not been fully scrutinized.

Methods And Results: We identified 1744 patients with heart failure and ejection fraction ≥50% referred for cardiopulmonary stress testing at the Cleveland Clinic (Cleveland, OH), 239 of whom had AF. We used inverse probability of treatment weighting to balance clinical characteristics between patients with and without AF. A weighted linear regression model, adjusted for unbalanced variables (age, sex, diagnosis, hypertension, and β-blocker use), was used to compare metabolic stress parameters and 8-year total mortality (social security index) between both groups. Weighted mean ejection fraction was 58±5.9% in the entire population. After adjusting for unbalanced weighted variables, patients with AF versus those without AF had lower mean peak oxygen consumption (18.5±6.2 versus 20.3±7.1 mL/kg per minute), oxygen pulse (12.4±4.3 versus 12.9±4.7 mL/beat), and circulatory power (2877±1402 versus 3351±1788 mm Hg·mL/kg per minute) (<0.001 for all comparisons) but similar submaximal exercise capacity (oxygen consumption at anaerobic threshold, 12.0±5.1 versus 12.4±6.0mL/kg per minute; =0.3). Both groups had similar peak heart rate, whereas mean peak systolic blood pressure was lower in the AF group (150±35 versus 160±51 mm Hg; <0.001). Moreover, AF was associated with higher total mortality.

Conclusions: In the largest study of its kind, we demonstrate that AF is associated with peak exercise intolerance, impaired contractile reserve, and increased mortality in patients with heart failure with preserved ejection fraction. Whether AF is the primary offender in these patients or merely a bystander to worse diastolic function requires further investigation.
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http://dx.doi.org/10.1161/JAHA.117.006662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721762PMC
October 2017

Accuracy of low-density lipoprotein cholesterol estimation at very low levels.

BMC Med 2017 04 20;15(1):83. Epub 2017 Apr 20.

Ciccarone Center for the Prevention of Heart Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Carnegie 591, Baltimore, MD, 21287, USA.

Background: As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate.

Methods: In 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation. We examined differences (estimate minus ultracentrifugation) and classification according to levels initiating additional safety precautions per clinical practice guidelines.

Results: Friedewald values were less than ultracentrifugation measurement, with a median difference (25th to 75th percentile) of -2.4 (-7.4 to 0.6) at 50-69 mg/dL, -7.0 (-16.2 to -1.2) at 25-39 mg/dL, and -29.0 (-37.4 to -19.6) at < 15 mg/dL. The respective values by novel estimation were -0.1 (-1.5 to 1.3), -1.1 (-2.5 to 0.3), and -2.7 (-4.9 to 0.0) mg/dL. Among those with Friedewald LDL-C < 15, 15 to < 25, and 25 to < 40 mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation.

Conclusions: Estimation of even lower LDL-C values (by Friedewald and novel methods) is even more inaccurate. More often than not, a Friedewald value < 40 mg/dL is underestimated, which translates into unnecessary safety alarms that could be reduced in half by estimation using our novel method.
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http://dx.doi.org/10.1186/s12916-017-0852-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399386PMC
April 2017

Evaluating Precision Medicine's Ability to Improve Population Health.

JAMA 2017 01;317(4):440-441

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.

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http://dx.doi.org/10.1001/jama.2016.20000DOI Listing
January 2017

Non-HDL Cholesterol and Triglycerides: Implications for Coronary Atheroma Progression and Clinical Events.

Arterioscler Thromb Vasc Biol 2016 11 11;36(11):2220-2228. Epub 2016 Aug 11.

From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).

Objectives: Non-high-density lipoprotein cholesterol (non-HDLC) levels reflect the full burden of cholesterol transported in atherogenic lipoproteins. Genetic studies suggest a causal association between elevated triglycerides (TGs)-rich lipoproteins and atherosclerosis. We evaluated associations between achieved non-HDLC and TG levels on changes in coronary atheroma volume.

Approach And Results: Data were analyzed from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and were evaluated against on-treatment non-HDLC and TG levels. The effects of lower (<100 mg/dL) versus higher (≥100 mg/dL) achieved non-HDLC levels and lower (<200 mg/dL) versus higher (≥200 mg/dL) achieved TG levels were evaluated in populations with variable on-treatment low-density lipoprotein cholesterol (LDLC) 0) was associated with achieved TG levels >200 mg/dL, respectively. Lower on-treatment non-HDLC and TG levels associated with significant PAV regression compared with higher non-HDLC and TG levels across all levels of LDLC and C-reactive protein and irrespective of diabetic status (P<0.001 across all comparisons). ΔPAV were more strongly influenced by changes in non-HDLC (β=0.62; P<0.001) compared with changes in LDLC (β=0.51; P<0.001). Kaplan-Meier sensitivity analyses demonstrated significantly greater major adverse cardiovascular event rates in those with higher versus lower non-HDLC and TG levels, with an earlier separation of the non-HDLC compared with the LDLC curve.

Conclusions: Achieved non-HDLC levels seem more closely associated with coronary atheroma progression than LDLC. Plaque progression associates with achieved TGs, but only above levels of 200 mg/dL. These observations support a more prominent role for non-HDLC (and possibly TG) lowering in combating residual cardiovascular risk.
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http://dx.doi.org/10.1161/ATVBAHA.116.307601DOI Listing
November 2016
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