Publications by authors named "Renato Quispe"

49 Publications

The Use of Blood Biomarkers in Precision Medicine for the Primary Prevention of Atherosclerotic Cardiovascular Disease: a Review.

Expert Rev Precis Med Drug Dev 2021 26;6(4):247-258. Epub 2021 May 26.

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

Introduction: A biomarker is a substance, structure, or process that indicates the presence of a disease, infection, or environmental exposure. Clinically useful biomarkers are measurable, improve diagnostic or prognostic performance, and ultimately aid clinicians in determining the initiation, duration, or magnitude of therapy.

Areas Covered: The purpose of this review is to explore the roles of various blood biomarkers of atherosclerotic cardiovascular disease (ASCVD) and how their use may improve the precision with which clinicians can identify, treat, and ultimately prevent ASCVD. Our review will include lipid biomarkers, markers of cardiac injury and wall stress, markers of inflammation, and a few others.

Expert Opinion: Several biomarkers have recently been highlighted as "risk-enhancing factors" in the 2019 American College of Cardiology/American Heart Association Guideline for the Primary Prevention of ASCVD, which can help guide shared decision-making. These included elevated low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, or high-sensitivity C-reactive protein. However, some other biomarkers mentioned in this review are not commonly used despite showing initial promise as prognostic of ASCVD risk, as it is not clear how treatment decisions should be changed after their measurement among asymptomatic individuals. Future studies should focus on whether biomarker-directed management strategies can improve clinical outcomes.
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http://dx.doi.org/10.1080/23808993.2021.1930531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372373PMC
May 2021

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

Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside.

Drug Des Devel Ther 2021 10;15:1955-1963. Epub 2021 May 10.

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

Bempedoic acid is a first-in-class, oral, inhibitor of cholesterol biosynthesis that is approved for use in patients with atherosclerotic cardiovascular disease (ASCVD) and for primary prevention in individuals with heterozygous familial hypercholesterolemia (HeFH) by the United States Food and Drug Administration. Pooled data from the phase III clinical trials, CLEAR Harmony and CLEAR Wisdom, have demonstrated the safety and efficacy of bempedoic acid with regard to lowering of low-density lipoprotein cholesterol (LDL-C) in patients with HeFH as an adjunct or alternative to currently existing lipid-lowering therapies. CLEAR Outcomes is a cardiovascular outcomes trial that is currently underway that will provide additional insight as to where bempedoic acid will fit into treatment regimens among the non-statin lipid-lowering therapy options. Patients who might particularly benefit from bempedoic acid are those with HeFH and those unable to take adequate doses of statins or take any statin therapy altogether who need additional LDL-C lowering. In this review, we will discuss the profile of bempedoic acid from its design, development, and its place in therapy for the management of LDL-C for the purposes of ASCVD prevention.
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http://dx.doi.org/10.2147/DDDT.S251865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121276PMC
May 2021

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia).

Arch Med Sci 2020 2;16(5):993-1003. Epub 2019 Aug 2.

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

Introduction: Dysbetalipoproteinaemia (HLP3) is a disorder characterized by excess cholesterol-enriched, triglyceride-rich lipoprotein remnants in genetically predisposed individuals that powerfully promote premature cardiovascular disease if untreated. The current prevalence of HLP3 is largely unknown.

Material And Methods: We performed cross-sectional analysis of 128,485 U.S. adults from the Very Large Database of Lipids (VLDbL), using four algorithms to diagnose HLP3 employing three Vertical Auto Profile ultracentrifugation (UC) criteria and a previously described apolipoprotein B (apoB) method. We evaluated 4,926 participants from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) with the apoB method. We examined demographic and lipid characteristics stratified by presence of HLP3 and evaluated lipid characteristics in those with HLP3 phenotype discordance and concordance as determined by apoB and originally defined UC criteria 1.

Results: In U.S. adults in VLDbL and NHANES, a 1.7-2.0% prevalence is observed for HLP3 with the novel apoB method as compared to 0.2-0.8% prevalence in VLDbL via UC criteria 1-3. Participants who were both apoB and UC criteria HLP3 positive had higher remnant particles as well as more elevated triglyceride/apoB and total cholesterol/apoB ratios (all < 0.001) than those who were apoB method positive and UC criteria 1 negative.

Conclusions: HLP3 may be more prevalent than historically and clinically appreciated. The apoB method increases HLP3 identification via inclusion of milder phenotypes. Further work should evaluate the clinical implications of HLP3 diagnosis at various lipid algorithm cut-points to evaluate the ideal standard in the modern era.
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http://dx.doi.org/10.5114/aoms.2019.86972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444722PMC
August 2019

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

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

Characterization of lipoprotein profiles in patients with hypertriglyceridemic Fredrickson-Levy and Lees dyslipidemia phenotypes: the Very Large Database of Lipids Studies 6 and 7.

Arch Med Sci 2019 Sep 22;15(5):1195-1202. Epub 2019 Aug 22.

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

Introduction: The association between triglycerides (TG) and cardiovascular diseases is complex. The classification of hypertriglyceridemic (HTG) phenotypes proposed by Fredrickson, Levy and Lees (FLL) helps inform treatment strategies. We aimed to describe levels of several lipoprotein variables from individuals with HTG FLL phenotypes from the Very Large Database of Lipids.

Material And Methods: We included fasting samples from 979,539 individuals from a contemporary large study population of US adults. Lipids were directly measured by density-gradient ultracentrifugation using the Vertical Auto Profile test while TG levels were measured in whole plasma using the Abbott ARCHITECT C-8000 system. Hyperchylomicronemic (Hyper-CM) and non-chylomicronemic (non-CM) phenotypes were defined using computationally derived models. Individuals with FLL type IIa phenotype were excluded. Distributions of lipid variables were compared using medians and Kruskal-Wallis test.

Results: A total of 11.9% ( = 116,925) of individuals met criteria for HTG FLL phenotypes. Those with hyper-CM phenotypes ( = 5, < 0.1% of population) had two-fold higher TG levels compared with non-chylomicronemic (non-CM) individuals (11.9% of population) ( < 0.001). Type IIb individuals had the highest non-HDL-C levels (median 242 mg/dl). Cholesterol in large VLDL particles was higher than in small VLDL particles in all phenotypes except FLL type III. Hyper-CM phenotypes had significantly lower HDL-C levels but greater HDL/HDL-C ratio compared to non-CM phenotypes. Cholesterol content of the lipoprotein (a) peak was significantly higher in the hyper-CM groups compared to non-CM phenotypes ( < 0.0001).

Conclusions: This observational hypothesis-generating study provides insight into the complexity of lipid metabolism in HTG phenotypes, including less traditional lipid measures such as LDL density, HDL subclasses and Lp(a)-C.
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http://dx.doi.org/10.5114/aoms.2019.87207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764300PMC
September 2019

Modern prevalence of the Fredrickson-Levy-Lees dyslipidemias: findings from the Very Large Database of Lipids and National Health and Nutrition Examination Survey.

Arch Med Sci 2020 3;16(6):1279-1287. Epub 2019 Aug 3.

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

Introduction: Five decades ago, Fredrickson, Levy, and Lees (FLL) qualitatively characterized clinical dyslipidemias with specific implications for cardiovascular and non-cardiovascular morbidity and mortality. They separated disorders of elevated cholesterol and triglycerides into five phenotypes (types I-V) based on their lipoprotein profile. Although clinicians generally consider them rare entities, modern FLL prevalence may be greater than previously reported.

Material And Methods: We performed a cross-sectional analysis in 5,272 participants from the 2011-2014 National Health and Nutrition Examination Survey and 128,506 participants from the Very Large Database of Lipids study with complete, fasting lipid profiles. We used a validated algorithm to define FLL phenotypes employing apolipoprotein B, total cholesterol, and triglycerides.

Results: Overall prevalence of FLL phenotypes was 33.9%. FLL prevalence in the general population versus clinical lipid database was: type I (0.05 vs. 0.02%), type IIa (3.2 vs. 3.9%), type IIb (8.0 vs. 10.3%), type III (2.0 vs. 1.7%), type IV (20.5 vs. 24.1%), and type V (0.15 vs. 0.13%). Those aged 40-74 years had a higher overall prevalence compared to other age groups ( < 0.001) and men had overall higher prevalence than women ( < 0.001). Those with diabetes (51.6%) or obese BMI (49.0%) had higher prevalence of FLL phenotypes compared to those without diabetes (31.3%; < 0.001) and normal BMI (18.3%; < 0.001).

Conclusions: FLL phenotypes are likely far more prevalent than appreciated in clinical practice, in part due to diabetes and obesity epidemics. Given the prognostic and therapeutic importance of these phenotypes, their identification becomes increasingly important in the era of precision medicine.
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http://dx.doi.org/10.5114/aoms.2019.86964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667447PMC
August 2019

Comparing different assessments of remnant lipoprotein cholesterol: The very large database of lipids.

J Clin Lipidol 2019 Jul - Aug;13(4):634-644. Epub 2019 Jun 11.

Ciccarone Center for Prevention of Heart Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Remnant lipoprotein cholesterol (RLP-C) is a risk factor for atherosclerotic cardiovascular disease, but there is no standard method for measurement. Some studies have used very low-density lipoprotein cholesterol estimated by the Friedewald equation to approximate RLP-C using a basic lipid panel, whereas others have attempted to measure RLP-C with ultracentrifugation.

Objective: The aim of the study was to compare RLP-C levels estimated from basic lipid parameters to those measured by ultracentrifugation.

Methods: We analyzed 1,350,908 individuals from the Very Large Database of Lipids, comparing one estimate of RLP-C using basic lipid parameters (RLP-C = non-high-density lipoprotein cholesterol - Friedewald-estimated low-density lipoprotein cholesterol for triglycerides <355 mg/dL [4 mmol/L], or non-high-density lipoprotein - directly measured low-density lipoprotein for triglycerides ≥355 mg/dL) to levels measured by vertical auto profile ultracentrifugation (RLP-C = dense subfraction of very low-density lipoprotein cholesterol + intermediate-density lipoprotein cholesterol). We calculated correlations between RLP-C and RLP-C along with median within-subject differences between RLP-C and RLP-C across quintiles of RLP-C. We also assessed correlations with RLP-C estimated from basic lipid parameters using a novel method of calculating low-density lipoprotein cholesterol with a patient-specific conversion factor (RLP-C).

Results: Our cohort was 48% male, and median (interquartile range) age was 59 (49-69) years. Median (interquartile range) RLP-C and RLP-C were 23 (16.4-33.2) and 24 (19-32) mg/dL, respectively. The correlation between RLP-C and RLP-C was 0.76. Based on the specified definition of RLP-C, the correlation between RLP-C and triglyceride/5 for triglyceride < 355 mg/dL was exactly 1.0. RLP-C was lower than RLP-C in the first and second quintiles of RLP-C but greater in the highest quintile. The correlations with RLP-C were 0.98 and 0.81 for RLP-C and RLP-C, respectively.

Conclusions: A previously used estimate of RLP-C using basic lipid parameters correlates weakly with remnants measured by ultracentrifugation. Our findings emphasize the need to standardize definitions and measurements of RLP-C.
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http://dx.doi.org/10.1016/j.jacl.2019.06.001DOI Listing
June 2020

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

Racial differences and mortality risk in patients with heart failure and hyponatremia.

PLoS One 2019 19;14(6):e0218504. Epub 2019 Jun 19.

Department of Medicine, Division of General Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States of America.

Background: Hyponatremia is a well-established poor prognostic marker in patients with heart failure. Whether the mortality risk is comparable among different races of patients with heart failure and hyponatremia is unknown.

Materials And Methods: Consecutive patients admitted with acute decompensated heart failure and an admission sodium level<135 mEq/L from 1/1/2001 through 12/31/10 were identified. Patients were divided into four groups based on self-reported race: white, African American, Hispanic and other. African Americans were used as the reference group for statistical analysis. The primary outcome was all-cause mortality.

Results: We included 4,343 patients, from which 1,356 (31%) identified as white, 1,248 (29%) as African American, 780 (18%) as Hispanic and 959 (22%) as other. During a median follow-up of 23 months, a total of 2,384 patients died: 678 were African American, 820 were white, 298 were Hispanic and 588 were other. After adjusting for baseline demographics, comorbidities and medication use, Hispanic patients had a 45% less risk of death as compared to African Americans (HR .55, CI .48-.64, p<0.05). There was no difference in mortality between white and African American patients (HR 1.04, CI .92-1.2, p = 0.79).

Conclusion: Hispanic patients admitted for heart failure and who were hyponatremic on admission had an independent lower risk of mortality compared to other groups. These findings may be due to the disparate activity of the renin-angiotensin-aldosterone system among various racial groups. This observational study is hypothesis generating and suggests that treatment of patients with heart failure and hyponatremia should perhaps be focused more on renin-angiotensin-aldosterone system reduction in certain racial groups, yet less in others.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218504PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583993PMC
February 2020

Clinical Characteristics of Young Patients With Heart Failure With Reduced Ejection Fraction in a Racially Diverse Cohort.

Crit Pathw Cardiol 2019 06;18(2):80-85

Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.

Background: Information on the clinical and echocardiographic characteristics of young patients with heart failure with reduced ejection fraction is scant, especially among racially diverse populations.

Methods: Patients admitted to Montefiore Medical Center between 2000 and 2016 with heart failure and ejection fraction of <40% were categorized as young (18-39 years), middle-aged (40-64 years), and elderly (≥65 years). Multivariable Cox regression models were used to evaluate mortality risk.

Results: A total of 1032 young, 8336 middle-aged, and 13,315 elderly patients were included. Median follow-up was 36 (14-69) months. The young group had more black individuals, lower socioeconomic scores, larger left ventricular chambers, but lower N-terminal pro b-type natriuretic peptide levels (P < 0.001). Better survival outcomes were observed in the young compared to the middle-aged [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.31-1.77] and elderly (HR, 3.19; 95% CI, 2.75-3.70). After multivariable adjustments, only β-blockers were associated with a significant reduction of mortality in young patients (HR, 0.33; 95% CI, 0.22-0.51).

Conclusion: In conclusion, young patients with heart failure with reduced ejection fraction have distinct demographic, clinical, and echocardiographic characteristics. They had lower socioeconomic status yet received more aggressive treatments and had lower mortality rates. Only β-blockers were associated with improved survival in young patients from our cohort.
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http://dx.doi.org/10.1097/HPC.0000000000000172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553968PMC
June 2019

Racial differences of heart failure with midrange ejection fraction (HFmrEF): a large urban centre-based retrospective cohort study in the USA.

BMJ Open 2019 05 1;9(4):e026479. Epub 2019 May 1.

Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.

Objectives: We aimed to study the racial differences in clinical presentations, survival outcomes and outcome predictors among patients with heart failure (HF) with midrange ejection fraction (HFmrEF, EF 40%-49%).

Design: This is a retrospective study.

Setting: Adults with HF diagnosis at Montefiore Medical Center, Bronx, New York between 2008 and 2012, with an inpatient echocardiogram showing left ventricular ejection fraction of 40%-49% were included as HFmrEF population.

Participants: 1,852 HFmrEF patients are included in the study (56% male, mean age 67 years). There were 493 (26.5%) non-Hispanic whites, 541 (29.2%) non-Hispanic black, 489 (26.4%) Hispanics and 329 (17.8%) other racial populations.

Outcome Measures: Cumulative probabilities of all-cause mortality among different racial groups were estimated and multivariable adjusted Cox proportional regressions were performed to assess predictors of mortality.

Results: Among the HFmrEF patients, white patients were older and were less likely to be on guideline-directed medications. Blacks had a lower prevalence of prior myocardial infarction comparing to other groups. Hispanics had more chronic diseases and yet better survival comparing to whites and blacks after adjustment for age, sex and comorbidities. Distinct sets of survival predictors were revealed in individual racial groups. Baseline use of mineralocorticoid receptor antagonist (MRA) was associated with lower mortality among HFmrEF patients in general (HR 0.61, 95% CI 0.37 to 0.99).

Conclusions: There are significant racial/ethnic differences in clinical phenotypes, survival outcomes and mortality predictors of HFmrEF. Furthermore, the use of MRA predicted a reduced mortality in HFmrEF patients.
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http://dx.doi.org/10.1136/bmjopen-2018-026479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501992PMC
May 2019

Breast Arterial Calcium: A Game Changer in Women's Cardiovascular Health?

JACC Cardiovasc Imaging 2019 12 13;12(12):2538-2548. Epub 2019 Mar 13.

Department of Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, Maryland; Cardiology Department, Bellvitge University Hospital and Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain; Research Triangle Institute Health Solutions, Pharmacoepidemiology and Risk Management, Barcelona, Spain. Electronic address:

In 2018, cardiovascular disease (CVD) was the leading cause of death among women, and current CVD prevention paradigms may not be sufficient in this group. In that context, it has recently been proposed that detection of calcification in breast arteries may help improve CVD risk screening and assessment in apparently healthy women. This review provides an overview of breast arterial anatomy; and the epidemiology, pathophysiology, and measurement of breast artery calcium (BAC); and discusses the features of the BAC-CVD link. The potential clinical applications that BAC may offer for CVD prevention in the context of current clinical practice guidelines and recommendations are also discussed. Finally, current gaps in evidence gaps are outlined, and future directions in the field are explored with a focus on the implementation of BAC mammography as a CVD risk-screening tool in routine clinical practice.
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http://dx.doi.org/10.1016/j.jcmg.2018.07.035DOI Listing
December 2019

A risk score for predicting atrial fibrillation in individuals with preclinical diastolic dysfunction: a retrospective study in a single large urban center in the United States.

BMC Cardiovasc Disord 2019 02 27;19(1):47. Epub 2019 Feb 27.

Department of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Jack D. Weiler Hospital, 1825 Eastchester Rd, Bronx, NY, 10461, USA.

Background: Left ventricular diastolic dysfunction has been shown to associate with increased risk of atrial fibrillation (AF). We aimed to examine the predictors of AF in individuals with preclinical diastolic dysfunction (PDD) - diastolic dysfunction without clinical heart failure - and develop a risk score in this population.

Methods: Patients underwent echocardiogram from December 2009 to December 2015 showing left ventricular ejection fraction (LVEF) ≥ 50% and grade 1 diastolic dysfunction, without clinical heart failure, valvular heart disease or AF were included. Outcome was defined as new onset AF. Cumulative probabilities were estimated and multivariable adjusted competing-risks regression analysis was performed to examine predictors of incident AF. A predictive score model was constructed.

Results: A total of 9591 PDD patients (mean age 66, 41% men) of racial/ethnical diversity were included in the study. During a median follow-up of 54 months, 455 (4.7%) patients developed AF. Independent predictors of AF included advanced age, male sex, race, hypertension, diabetes, and peripheral artery disease. A risk score including these factors showed a Wolber's concordance index of 0.65 (0.63-0.68, p <  0.001), suggesting a good discrimination.

Conclusions: Our study revealed a set of predictors of AF in PDD patients. A simple risk score predicting AF in PDD was developed and internally validated. The scoring system could help clinical risk stratification, which may lead to prevention and early treatment strategies.
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http://dx.doi.org/10.1186/s12872-019-1024-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391831PMC
February 2019

Synergistic Opportunities in the Interplay Between Cancer Screening and Cardiovascular Disease Risk Assessment: Together We Are Stronger.

Circulation 2018 08;138(7):727-734

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology (C.E.H., R.Q., M.J.B., R.S.B., E.D.M., M.C.-A.).

Cardiovascular disease (CVD) and cancer continue to be the 2 leading causes of death in developed countries despite significant improvements in the prevention, screening, and treatment of both diseases. They remain significant public health problems, growing in importance globally. Despite this threat, the fields of cardiology and oncology have been relatively disconnected. With many shared modifiable risk factors, cancer and CVD often coexist in the same individuals; those diagnosed with lung cancer, breast cancer, and colon cancer are at higher risk of CVD, and those with CVD are at higher risk of developing many types of common cancers. Screening paradigms have been established in parallel, but there are opportunities for combined risk assessments for cancer and CVD risk. Joining forces for combined cardiovascular and hemato-oncological preventive and research efforts will likely have synergistic, worldwide public health benefits.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035516DOI Listing
August 2018

Bundle branch reentrant ventricular tachycardia: review and case presentation.

J Interv Card Electrophysiol 2018 Aug 28;52(3):385-393. Epub 2018 Aug 28.

Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY, 10467, USA.

Bundle branch reentrant ventricular tachycardia (BBRVT) is characterized by a unique, fast (200-300 beats/min), monomorphic wide complex tachycardia (WCT) associated with syncope, hemodynamic compromise, and cardiac arrest. It is challenging to diagnose, requiring a His bundle recording and specific pacing maneuvers. The overall incidence has been reported to be up to 20% among patients with non-ischemic cardiomyopathy (NICM) undergoing electrophysiologic studies. We report a case of BBRVT in a patient with ischemic cardiomyopathy (ICM) presenting as a WCT with recurrent implantable-cardioverter-defibrillator (ICD) shocks. We describe all the characteristic features of BBRVT and discuss its differential. We also discuss the role of ablation for this condition.
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http://dx.doi.org/10.1007/s10840-018-0434-zDOI Listing
August 2018

Clinical outcomes in patients with atrial fibrillation receiving amiodarone on NOACs vs. warfarin.

J Interv Card Electrophysiol 2019 Jan 20;54(1):73-80. Epub 2018 Aug 20.

Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY, 10467, USA.

Purpose: Amiodarone is a potent inhibitor of the CYP450:3A4 and inhibitor of the P-glycoprotein, both of which metabolize new oral anticoagulants (NOACs). Patients who are on NOACs and are concomitantly treated with amiodarone may have a higher risk of major bleeding according to recent retrospective trials. Whether this increased risk outweighs the benefits of NOACs compared to warfarin is unknown. We aimed to compare clinical outcomes between NOACs and warfarin in patients with atrial fibrillation (AF) being treated with amiodarone.

Methods: We performed a systematic review of MEDLINE, Cochrane, and Embase for randomized controlled trials that compared NOACs to warfarin for prophylaxis of ischemic stroke/thromboembolic events (TEs) in patients with AF and reported outcomes on TE, major bleeding, and intracranial bleeding (ICB). Risk ratio (RR) and 95% confidence intervals were measured using the Mantel-Haenszel method. Fixed effects model was used, and if heterogeneity (I2) was > 25%, effects were analyzed using a random model.

Results: A total of four studies comparing NOACs to warfarin were included in the analysis. The total number of patients on amiodarone was 6197. Mean follow up was 23 ± 5 months. No statistically significant difference for TE prevention (RR, 0.73; 95% CI 0.50-1.07), major bleeding (RR, 1.02; 95% CI 0.68-1.53), or ICB outcomes (RR, 0.58; 95% CI 0.22-1.51) between patients on NOACs + amiodarone when compared to patients on warfarin + amiodarone.

Conclusion: Among patients with AF taking amiodarone, there is no increased risk of stroke, major bleeding, or ICB with NOACs compared to warfarin.
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http://dx.doi.org/10.1007/s10840-018-0427-yDOI Listing
January 2019

Early Versus Late Referral for Catheter Ablation of Ventricular Tachycardia in Patients With Structural Heart Disease: A Systematic Review and Meta-Analysis of Clinical Outcomes.

JACC Clin Electrophysiol 2018 03 13;4(3):374-382. Epub 2018 Feb 13.

Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts; Department of Cardiology, Westmead Hospital, Westmead Applied Research Centre, University of Sydney, Westmead, New South Wales, Australia. Electronic address:

Objectives: This was a meta-analysis of published studies to examine the impact of early referral on outcomes after catheter ablation for ventricular tachycardia (VT) in patients with structural heart disease.

Background: Patients are frequently referred for VT ablation after failure of antiarrhythmic drugs to control VT. Some studies have suggested that early referral might confer better outcomes.

Methods: An electronic search was performed using major databases. The primary outcomes were long-term VT recurrence and total mortality. Secondary outcomes were acute procedural success and acute complications.

Results: Three studies were included with a total of 980 patients (mean age 64 ± 12 years, 71% males). Mean follow-up was 29 ± 27 months. Early referral for VT ablation was associated with decreased VT recurrence and acute complications compared with late referral (relative risk: 0.69 [95% confidence interval: 0.58 to 0.82], p < 0.0001 and relative risk: 0.50 [95% confidence interval: 0.27 to 0.93], p = 0.03, respectively). There was no significant difference between early and late referral for total mortality and acute success.

Conclusions: Late referral for VT ablation was associated with worse outcomes (VT recurrence and acute complications) in patients with structural heart disease, which suggests that early referral for VT ablation might be a reasonable consideration in this patient population.
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http://dx.doi.org/10.1016/j.jacep.2017.12.008DOI Listing
March 2018

Coronary Artery Calcium Score: the "Mammogram" of the Heart?

Curr Cardiol Rep 2018 07 10;20(9):70. Epub 2018 Jul 10.

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

Purpose Of Review: To discuss the classic analogy of "coronary artery calcium (CAC) as a mammogram of the heart", by evaluating the conceptual strengths, weaknesses, opportunities, and threats of a potential cardiovascular disease (CVD) screening strategy using CAC in apparently healthy adults.

Recent Findings: CAC is typically used for further CVD risk assessment. CAC is also currently being used as a screening test in specific subgroups of individuals, particularly in some Asian countries. Although this has yielded valuable insights on the determinants and pathophysiology of CVD, whether this approach results in improved clinical outcomes compared to other assessment and management approaches is currently unclear. Although CAC and mammograms share a number of characteristics, there are also important conceptual differences. The evidence supporting CAC, which is a robust CVD risk assessment tool, for CVD screening purposes is currently very limited, and further research is needed.
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http://dx.doi.org/10.1007/s11886-018-1020-9DOI 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

Clinical impact of implantable cardioverter-defibrillator in primary prevention of total mortality in non-ischaemic cardiomyopathy: results from a meta-analysis of prospective randomized clinical trials.

Europace 2018 09;20(FI2):f211-f216

Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY, USA.

Aim: Primary prophylactic implantable cardioverter defibrillators (ICDs) have demonstrated a clear all-cause mortality benefit in patients with ischaemic cardiomyopathy, with less compelling evidence supporting its use in patients with non-ischaemic cardiomyopathy (NICM). We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the role of ICD for reduction in total mortality in NICM patients.

Methods And Results: An electronic search on PubMed, the Cochrane Library, and EMBASE databases was performed to identify the RCTs evaluating the role of prophylactic ICD placement in NICM patients. Mantel-Haenszel risk ratio (RR) fixed-effects model was used to summarize data across treatment arms. Random-effects model was used if heterogeneity (I2) ≥ 25. Patients with cardiac resynchronization therapy pacemaker (CRT-P) were included in the control group. Six RCTs, with a total of 3128 patients and a mean follow-up period of 48 ± 22 months comparing ICD with medical therapy in NICM were included in this analysis. There was a significant reduction in all-cause mortality in the ICD group compared with the medical therapy group [RR 0.79, 95% confidence interval (95% CI) 0.68-0.92; P = 0.002]. No publication bias was noted.

Conclusion: Currently available evidence demonstrates that the use of ICD provides a clear and significant reduction in all-cause mortality among patients with NICM.
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http://dx.doi.org/10.1093/europace/eux324DOI Listing
September 2018

Parity and Overweight/Obesity in Peruvian Women.

Prev Chronic Dis 2017 10 19;14:E102. Epub 2017 Oct 19.

CRONICAS Centro de Excelencia en Enfermedades Crónicas, Universidad Peruana Cayetano Heredia, Ave Armendáriz 497, 2do piso, Miraflores, Lima 18, Peru. Email:

Introduction: The rise in noncommunicable diseases and their risk factors in developing countries may have changed or intensified the effect of parity on obesity. We aimed to assess this association in Peruvian women using data from a nationally representative survey.

Methods: We used data from Peru's Demographic and Health Survey, 2012. Parity was defined as the number of children ever born to a woman. We defined overweight as having a body mass index (BMI, kg/m) of 25.0 to 29.9 and obesity as a BMI ≥30.0. Generalized linear models were used to evaluate the association between parity and BMI and BMI categories, by area of residence and age, adjusting for confounders.

Results: Data from 16,082 women were analyzed. Mean parity was 2.25 (95% confidence interval [CI], 2.17-2.33) among rural women and 1.40 (95% CI, 1.36-1.43) among urban women. Mean BMI was 26.0 (standard deviation, 4.6). We found evidence of an association between parity and BMI, particularly in younger women; BMI was up to 4 units higher in rural areas and 2 units higher in urban areas. An association between parity and BMI categories was observed in rural areas as a gradient, being highest in younger women.

Conclusion: We found a positive association between parity and overweight/obesity. This relationship was stronger in rural areas and among younger mothers.
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http://dx.doi.org/10.5888/pcd14.160282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662294PMC
October 2017

Fasting Versus Nonfasting and Low-Density Lipoprotein Cholesterol Accuracy.

Circulation 2018 01 16;137(1):10-19. Epub 2017 Oct 16.

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (V.S., R.Q., R.S.B., S.R.J., S.S.M.).

Background: Recent recommendations favoring nonfasting lipid assessment may affect low-density lipoprotein cholesterol (LDL-C) estimation. The novel method of LDL-C estimation (LDL-C) uses a flexible approach to derive patient-specific ratios of triglycerides to very low-density lipoprotein cholesterol. This adaptability may confer an accuracy advantage in nonfasting patients over the fixed approach of the classic Friedewald method (LDL-C).

Methods: We used a US cross-sectional sample of 1 545  634 patients (959 153 fasting ≥10-12 hours; 586 481 nonfasting) from the second harvest of the Very Large Database of Lipids study to assess for the first time the impact of fasting status on novel LDL-C accuracy. Rapid ultracentrifugation was used to directly measure LDL-C content (LDL-C). Accuracy was defined as the percentage of LDL-C falling within an estimated LDL-C (LDL-C or LDL-C) category by clinical cut points. For low estimated LDL-C (<70 mg/dL), we evaluated accuracy by triglyceride levels. The magnitude of absolute and percent differences between LDL-C and estimated LDL-C (LDL-C or LDL-C) was stratified by LDL-C and triglyceride categories.

Results: In both fasting and nonfasting samples, accuracy was higher with the novel method across all clinical LDL-C categories (range, 87%-94%) compared with the Friedewald estimation (range, 71%-93%; ≤0.001). With LDL-C <70 mg/dL, nonfasting LDL-C accuracy (92%) was superior to LDL-C accuracy (71%; <0.001). In this LDL-C range, 19% of fasting and 30% of nonfasting patients had differences ≥10 mg/dL between LDL-C and LDL-C, whereas only 2% and 3% of patients, respectively, had similar differences with novel estimation. Accuracy of LDL-C <70 mg/dL further decreased as triglycerides increased, particularly for Friedewald estimation (range, 37%-96%) versus the novel method (range, 82%-94%). With triglycerides of 200 to 399 mg/dL in nonfasting patients, LDL-C <70 mg/dL accuracy (82%) was superior to LDL-C (37%; <0.001). In this triglyceride range, 73% of fasting and 81% of nonfasting patients had ≥10 mg/dL differences between LDL-C and LDL-C compared with 25% and 20% of patients, respectively, with LDL-C.

Conclusions: Novel adaptable LDL-C estimation performs better in nonfasting samples than the fixed Friedewald estimation, with a particular accuracy advantage in settings of low LDL-C and high triglycerides. In addition to stimulating further study, these results may have immediate relevance for guideline committees, laboratory leadership, clinicians, and patients.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01698489.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030677DOI Listing
January 2018

Home Blood Pressure Management Intervention in Low- to Middle-Income Countries: Protocol for a Mixed Methods Study.

JMIR Res Protoc 2017 Oct 16;6(10):e188. Epub 2017 Oct 16.

Department of Cardiology, Hospital Universitario Lucus Augusti, Lugo, Spain.

Background: Control of hypertension in low- and middle-income countries (LMICs) is poor, often less than 10%. A strong body of evidence demonstrates that home blood pressure management lowers blood pressure, and recent guidelines from the National Institute for Clinical Health and Excellence recommends home blood pressure monitoring. However, the preponderance of data on the benefits of home blood pressure management comes from studies in high-income countries.

Objective: The objective of the study is to examine whether an intervention of home blood pressure management is feasible in LMICs. Home blood pressure management is defined as self-monitoring of blood pressure and self-titration of antihypertensive medications. We will identify barriers and facilitators of home blood pressure management and explore unique contextual factors in LMICs that influence implementation of home blood pressure management.

Methods: Participants will be recruited from 6 sites from 2015 to 2018. Patients and health care workers will be included. We will use mixed methods including focus groups, interviews, and standardized checklists. When possible, we will adapt materials from prior successful studies so that they are culturally and contextually appropriate.

Results: This ongoing study is funded by the World Heart Federation. The information that is obtained will be used to develop a randomized clinical trial of home blood pressure management in LMICs.

Conclusions: The data generated from this qualitative study will provide much needed information from patients and health care workers about barriers and facilitators of home blood pressure management and unique contextual factors that might influence implementation of home blood pressure management in LMICs.
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http://dx.doi.org/10.2196/resprot.7148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662792PMC
October 2017

Urbanization, mainly rurality, but not altitude is associated with dyslipidemia profiles.

J Clin Lipidol 2017 Sep - Oct;11(5):1212-1222.e4. Epub 2017 Jul 5.

CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru; Department of Medicine, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru. Electronic address:

Background: Geographical and environmental features such as urbanization and altitude may influence individual's lipid profiles because of the diversity of human-environment interactions including lifestyles.

Objective: To characterize the association between altitude and urbanization and lipid profile among Peruvian adults aged ≥35 years.

Methods: Cross-sectional analysis of the CRONICAS Cohort Study. The outcomes of interest were 6 dyslipidemia traits: hypertriglyceridemia, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol (HDL-c), nonisolated low HDL-c, isolated low HDL-c, and high non-HDL-c. The exposures of interest were urbanization level (highly urban, urban, semi-urban, and rural) and altitude (high altitude vs sea level). Prevalence ratios (PRs) and 95% confidence intervals (95% CIs) were calculated using Poisson regression models with robust variance adjusting for potential confounders.

Results: Data from 3037 individuals, 48.5% males, mean age of 55.6 (standard deviation ±12.7) years, were analyzed. The most common dyslipidemia pattern was high non-HDL-c with a prevalence of 88.0% (95% CI: 84.9%-90.7%) in the rural area and 96.0% (95% CI: 94.5%-97.1%) in the semi-urban area. Relative to the highly urban area, living in rural areas was associated with a lower prevalence of hypertriglyceridemia (PR = 0.75; 95% CI: 0.56-0.99) and high non-HDL-c (PR = 0.96; 95% CI: 0.93-0.99), whereas living in semi-urban areas was associated with higher prevalence high low-density lipoprotein cholesterol (PR = 1.37; 95% CI: 1.11-1.67). Compared with sea level areas, high-altitude areas had lower prevalence of high non-HDL-c (PR = 0.97; 95% CI: 0.95-0.99).

Conclusion: Urbanization but not altitude was associated to several dyslipidemia traits, with the exception of high non-HDL-c in high altitude settings.
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http://dx.doi.org/10.1016/j.jacl.2017.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624786PMC
May 2018

Vitamin D deficiency and non-lipid biomarkers of cardiovascular risk.

Arch Med Sci 2017 Jun 12;13(4):732-737. Epub 2017 Jun 12.

Ciccarone Center for Prevention of Heart Disease, Johns Hopkins University, Baltimore, MD, USA.

Introduction: Deficient 25-hydroxyvitamin D (25(OH)D) levels have been associated with dyslipidemia and cardiovascular diseases, though the underlying mechanism of these associations is uncertain. We analyzed associations between vitamin D and other non-lipid biomarkers of cardiovascular risk to better elucidate possible relationships between deficient 25(OH)D and cardiovascular disease.

Material And Methods: We performed a cross-sectional analysis of 4,591 adults included in a clinical laboratory database from 2009 to 2011 with available measurements for 25(OH)D and the following biomarkers: homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), cystatin-C, creatinine, γ-glutamyltransferase (GGT), uric acid, and hemoglobin A (HbA). We calculated odds ratios (OR) of having high levels of each biomarker associated with 25(OH)D deficiency (< 20 ng/ml) compared to optimal levels (≥ 30 ng/ml) using logistic regression adjusted for age, sex, and lipids.

Results: The mean ± SD age was 60 ±14 years and 46% of patients were women. In multivariable-adjusted models, adults with deficient 25(OH)D compared to those with optimal levels had increased odds of elevated biomarkers as follows: Hcy (OR = 2.53, 95% CI: 1.92-3.34), hs-CRP (1.62, 1.36-1.93), cystatin-C (2.02, 1.52-2.68), creatinine (2.06, 1.35-3.14), GGT (1.39, 1.07-1.80), uric acid (1.60, 1.31-1.95), and HbA (2.47, 1.95-3.13). In analyses evaluating women and men separately, 25(OH)D deficient women but not men had increased odds of elevated levels of all biomarkers studied. There were significant interactions based on sex between 25(OH)D and Hcy ( = 0.003), creatinine ( = 0.004), uric acid ( = 0.040), and HbA ( = 0.037).

Conclusions: Deficient 25(OH)D is associated with elevated levels of many biomarkers of cardiovascular risk, particularly among women, in a United States population.
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http://dx.doi.org/10.5114/aoms.2017.68237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510501PMC
June 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
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