Publications by authors named "Nathan D Wong"

362 Publications

The potential population health impact of treating REDUCE-IT eligible US adults with Icosapent Ethyl.

Am J Prev Cardiol 2022 Jun 28;10:100345. Epub 2022 Apr 28.

MedStar Health Research Institute, Georgetown University, Washington, DC.

Objective: To explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs.

Methods: We derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from the ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE therapy. The National Inpatient Sample estimated event costs (facility and professional) and daily IPE treatment cost was approximated at $4.59.

Results: We estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion).

Conclusions: Treating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.
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http://dx.doi.org/10.1016/j.ajpc.2022.100345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097618PMC
June 2022

Detecting Coronary Calcium in Young Adults: Are We There Yet?

J Am Coll Cardiol 2022 May;79(19):1887-1889

Division of Cardiology, University of California-Irvine, Irvine, California, USA. Electronic address: https://twitter.com/DrNathanWong.

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http://dx.doi.org/10.1016/j.jacc.2022.03.333DOI Listing
May 2022

Evidence for intensive LDL-C lowering for acute coronary syndrome: Recommendations from the Lipid Association of India.

J Clin Lipidol 2022 Mar 25. Epub 2022 Mar 25.

Heart Disease Prevention Program Division of Cardiology, University of California Irvine, USA.

Patients with acute coronary syndrome (ACS) have a high risk of subsequent adverse cardiovascular outcomes, particularly within the first 30 days. Although it is well documented that initiation of statin therapy in the setting of ACS improves short- and long-term cardiovascular outcomes, and achievement of lower levels of low density lipoprotein cholesterol (LDL-C) incrementally improves outcomes, many patients with ACS have persistent hypercholesterolemia after discharge from the hospital. This is a missed opportunity that prompted the Lipid Association of India to develop recommendations for earlier initiation of more aggressive LDL-C lowering treatment, particularly for patients of South Asian descent who are well-documented to have earlier onset of more aggressive atherosclerotic cardiovascular disease. The Lipid Association of India recommends individualized aggressive LDL-C goals after ACS, which can be rapidly achieved with high intensity statin therapy and subsequent goal-directed adjunctive treatment with ezetimibe and PCSK9 inhibitors. Improved treatment of hypercholesterolemia achieved within weeks after ACS has the potential to reduce the high rate of morbidity and mortality in these high risk patients.
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http://dx.doi.org/10.1016/j.jacl.2022.03.008DOI Listing
March 2022

Acute coronary syndromes in diabetes: Biomarkers of endothelial injury improve risk stratification and help identify predictors of risk.

Diabetes Metab Syndr 2022 Apr 28;16(4):102476. Epub 2022 Mar 28.

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine School of Medicine, Irvine, CA, United States. Electronic address:

Background And Aims: Patients with diabetes mellitus (DM) are at an increased risk of acute coronary syndrome (ACS); however, the factors predicting those at highest risk are not well understood. We identified risk factors in those with DM that best predict high ACS risk based on a multiple endothelial injury biomarker algorithm.

Methods: We studied adults with DM from a clinical registry with measures of a coronary artery disease prediction algorithm (CADPA) score identifying 5-year ACS risk from nine markers. Stepwise logistic regression provided odds ratios for the relationship of age, gender, and individual risk factors not part of the CADPA algorithm with the likelihood of a high risk CADPA score.

Results: We studied 1,613 adults with DM (women: 47.3%, ages 22 to 100, mean age 63.2 years). Of these, 6.1% had a low, 13.2% intermediate, and 80.7% high risk CADPA score. From stepwise logistic regression, women were less likely to have a high risk CADPA score (odds ratio [OR] 0.21, 95% confidence intervals [CI] 0.15-0.29, p<.0001), while age (per standard deviation [SD]) (OR 5.04, [4.12-6.17], p<.0001), body mass index (BMI per SD) (OR 1.34, [1.14-1.58], p = 0.004), hypertension (OR 1.60, [1.15-2.24], p = 0.006), current smoking (OR 2.55, [1.56-4.16], p = 0.0002), hsCRP (per SD) (OR 1.24, [1.01-1.53], p = 0.04), and triglycerides (per SD) (OR 1.26, [1.04-1.54], p = 0.02) were more likely to have a high risk CADPA score.

Conclusions: Age, men, hypertension, BMI, current smoking, hsCRP, and triglycerides are key factors in those with DM associated with higher ACS risk.
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http://dx.doi.org/10.1016/j.dsx.2022.102476DOI Listing
April 2022

Atherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement.

Am J Prev Cardiol 2022 Jun 15;10:100335. Epub 2022 Mar 15.

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

Risk for atherosclerotic cardiovascular disease (ASCVD) shows considerable heterogeneity both in generally healthy persons and in those with known ASCVD. The foundation of preventive cardiology begins with assessing baseline ASCVD risk using global risk scores based on standard office-based measures. Persons at low risk are generally recommended for lifestyle management only and those at highest risk are recommended for both lifestyle and pharmacologic therapy. Additional "risk enhancing" factors, including both traditional risk factors and novel biomarkers and inflammatory factors can be used to further assess ASCVD risk, especially in those at borderline or intermediate risk. There are also female-specific risk enhancers, social determinants of health, and considerations for high-risk ethnic groups. Screening for subclinical atherosclerosis, especially with the use of coronary calcium screening, can further inform the treatment decision if uncertain based on the above strategies. Persons with pre-existing ASCVD also have variable risk, affected by the number of major ASCVD events, whether recurrent events have occurred recently, and the presence of other major risk factors or high-risk conditions. Current guidelines define high to very high risk ASCVD accordingly. Accurate ASCVD risk assessment is crucial for the appropriate targeting of preventive therapies to reduce ASCVD risk. Finally, the clinician-patient risk discussion focusing on lifestyle management and the risks and benefits of evidence-based pharmacologic therapies to best lower ASCVD risk is central to this process. This clinical practice statement provides the preventive cardiology specialist with guidance and tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events.
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http://dx.doi.org/10.1016/j.ajpc.2022.100335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943256PMC
June 2022

Breast Arterial Calcification: a Novel Cardiovascular Risk Enhancer Among Postmenopausal Women.

Circ Cardiovasc Imaging 2022 03 15;15(3):e013526. Epub 2022 Mar 15.

Department of Radiological Sciences, University of California Irvine School of Medicine (F.F.A., H.D., S.M.).

Background: Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD.

Methods: A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD.

Results: Twenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; =0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; =0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; =0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; =0.04) after adding BAC status.

Conclusions: Our results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.
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http://dx.doi.org/10.1161/CIRCIMAGING.121.013526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931858PMC
March 2022

Relation of Progression of Coronary Artery Calcium to Dementia (from the Multi-Ethnic Study of Atherosclerosis).

Am J Cardiol 2022 May 11;171:69-74. Epub 2022 Mar 11.

Cardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, Washington.

Baseline coronary artery calcification has been shown to be associated with dementia. However, the value of coronary artery calcium (CAC) progression in the prediction of dementia remains unclear. In this study, we examined the association between CAC progression and dementia in the Multi-Ethnic Study of Atherosclerosis. The Multi-Ethnic Study of Atherosclerosis is a prospective study consisting of 6,814 participants 45 to 84 years of age, free of overt cardiovascular disease at baseline. A total of 5,570 subjects had baseline and follow-up CAC scans approximately 2.5 years apart and were included this analysis. A total of 4,173 of these participants completed cognitive testing with the Cognitive Abilities Screening Instrument (CASI) approximately 10 years after the baseline CAC scan. Dementia diagnoses were identified using International Classification of Diseases codes from hospitalizations, death certificates, and medications used to treat dementia. The absolute change between baseline and follow-up CAC was used to assess CAC progression. Cox proportional hazards and multivariable linear regression models were used to examine the association of CAC progression with incident dementia and with CASI score. Over a median follow-up of 13.2 (interquartile range: 11.2 to 15.3) years, 350 participants developed incident dementia. CAC progression showed no association with dementia risk after adjustment for age, gender, race/ethnicity, vascular risk factors, and baseline CAC score. There was no association of CAC progression with CASI score in any adjusted model. In conclusion, progression of CAC over approximately 2.5 years was not associated with increased risk of dementia after adjustment for demographic variables, vascular risk factors, and baseline CAC.
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http://dx.doi.org/10.1016/j.amjcard.2022.01.061DOI Listing
May 2022

Editors' page-March 2022.

Am J Prev Cardiol 2022 Mar 11;9:100320. Epub 2022 Feb 11.

Division of Cardiology, University of California, Irvine, United States.

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http://dx.doi.org/10.1016/j.ajpc.2022.100320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857603PMC
March 2022

Prevalence of statin intolerance: a meta-analysis.

Eur Heart J 2022 Feb 16. Epub 2022 Feb 16.

Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Rzgowska 281/289, 93-338 Lodz, Poland.

Aims: Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI.

Methods And Results: We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI.

Conclusion: Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

Key Question: What is the overall prevalence of statin intolerance (SI) worldwide? What are the main risk factors of SI?

Key Finding: The overall prevalence of SI is 9.1% and even lower using the international definitions: National Lipid Association, International Lipid Expert Panel, European Atherosclerosis Society (7.0, 6.7, 5.9%). Female gender, hypothyroidism, high statin dose, advanced age, antiarrhythmics, and obesity are the main factors that increase the risk of SI.

Take-home Message: Clinicians should use these results to encourage adherence to statin therapy in the patients they treat.
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http://dx.doi.org/10.1093/eurheartj/ehac015DOI Listing
February 2022

Temporal changes in risk of cardiovascular events in people with newly diagnosed type 2 diabetes with and without cardiovascular disease.

J Diabetes Complications 2022 02 10;36(2):108126. Epub 2022 Jan 10.

Department of Cardiology, Nordsjællands University Hospital, Dyrehavevej 29, 3400 Hillerød, Denmark; Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Hellerup, Denmark.

Aims: Examine temporal changes in the risk of cardiovascular events in people with newly diagnosed type 2 diabetes with and without cardiovascular disease (CVD).

Methods: 283,600 individuals with newly diagnosed type 2 diabetes and age-, sex-, and CVD-matched controls without diabetes were identified through Danish nationwide registries between 1997 and 2014. Using Cox regression models, we report the standardized absolute 5-year risk of cardiovascular death, myocardial infarction, stroke, and heart failure for people with diabetes and controls.

Results: Individuals with newly diagnosed diabetes were at increased risk of cardiovascular events compared to controls. From 1997-2002 to 2009-2014 reductions in cardiovascular events for people with diabetes were: cardiovascular death; 26.5% to 13.8% in people with CVD and from 7.3% to 3.2% in people without CVD, myocardial infarction; 13.1% to 6.5% in people with CVD and from 4.1% to 1.9% in people without CVD, stroke; 14.2% to 8.8% in people with CVD and from 4.9% to 2.2% in people without CVD, and heart failure; 21.0% to 13.8% in people with CVD and from 5.0% to 2.6% in people without CVD. The risk of cardiovascular events declined more among people with diabetes than controls.

Conclusions: Newly diagnosed type 2 diabetes was associated with an increased risk of cardiovascular events, and the risk decreased significantly 1997-2014 in both people with and without CVD. Furthermore, the excess risk associated with type 2 diabetes decreased significantly during the study period.
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http://dx.doi.org/10.1016/j.jdiacomp.2022.108126DOI Listing
February 2022

Editors' page.

Am J Prev Cardiol 2021 Dec 22;8:100297. Epub 2021 Nov 22.

Division of Cardiology, University of California Irvine School of Medicine, C240 Medical Sciences, University of California, Irvine, CA 92697, USA.

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http://dx.doi.org/10.1016/j.ajpc.2021.100297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714498PMC
December 2021

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Ann Intern Med 2022 04 4;175(4):574-589. Epub 2022 Jan 4.

National Heart, Lung, and Blood Institute, Bethesda, Maryland (S.C., Y.H.).

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.
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http://dx.doi.org/10.7326/M21-3729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018596PMC
April 2022

Association of inflammatory markers and lipoprotein particle subclasses with progression of coronary artery calcium: The multi-ethnic study of atherosclerosis.

Atherosclerosis 2021 12 4;339:27-34. Epub 2021 Nov 4.

Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.

Background And Aims: Atherosclerosis is a complex phenomenon manifesting several features typical of chronic inflammation and disorders of lipid metabolism. We assessed association of nuclear magnetic resonance (NMR) lipid variables and inflammatory markers with incident coronary artery calcium (CAC) and CAC progression among participants with baseline CAC ≥0.

Methods: MESA is a longitudinal cohort study of 6,814 participants (aged 45-85). 3,115 had CAC = 0 and 2,896 had CAC>0 at baseline. Repeat CAC measurements were obtained (mean duration of follow up, 6.5 years).

Results: IL-6 (log pg/mL) and fibrinogen (50 mg/dL) were associated with a higher relative risk (RR) of incident CAC (HU) (RR = 1.09, p=0.010 & RR 1.05, p=0.004, respectively). Small LDL (100 nmol/L) (RR = 1.03, p<0.001) and log large VLDL (log nmol/L) (RR = 1.06, p=0.001) were associated with higher risks, whereas large HDL (μmol/L) was associated with an inverse risk of incident CAC (RR = 0.97, p< 0.001) in a model adjusted for follow up time, age, gender and race. Among participants with baseline CAC>0, progression of CAC was positively associated with hsCRP (log mg/L) (β = 1.99), IL-6 (log pg/mL) (β = 2.9), fibrinogen (50 mg/dL) (β = 1.0), large VLDL (log nmol/L) (β = 2.2), and small LDL (100 nmol/L) (β = 0.36) (all p values < 0.05) in a model adjusted for scanner type, age, gender and race. Relationships with inflammatory markers and NMR lipoprotein particles lost significance after adjustment for traditional risk factors and statin use. Traditional risk factors were strongly associated with both CAC incidence and progression with the exception of cholesterol parameters not associated with CAC progression in adjusted model.

Conclusions: Inflammatory markers and lipoprotein particles were associated with CAC incidence and progression in minimally adjusted models, but not after adjustment for traditional risk factors.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.11.003DOI Listing
December 2021

Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India.

Curr Vasc Pharmacol 2022 ;20(2):134-155

Medicine and Preventive Cardiology, Arihant Hospital and Research Center, Indore, Madhya Pradesh, India.

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Nonstatin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals with statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).
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http://dx.doi.org/10.2174/1570161119666211109122231DOI Listing
May 2022

Association of cardiovascular health with mortality among COPD patients: National Health and Nutrition Examination Survey III.

Respir Med Res 2021 Nov 9;80:100860. Epub 2021 Sep 9.

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, CA, U SA. Electronic address:

Background: All-cause and cardiovascular disease (CVD) mortality are higher among patients with chronic obstructive pulmonary disease (COPD). We examined the association between American Heart Association's Life's Simple 7 (LS7) metrics and all-cause as well as CVD mortality in patients with COPD.

Methods: We examined 1513 US adults with COPD aged ≥ 40, without prior CVD, from the National Health and Nutrition Examination Survey III. COPD was defined as FEV/FVC<0.7 in absence of asthma. Adjusted Cox regression was used to assess the relation of LS7 metrics with all-cause and CVD mortality.

Results: Overall, only 74 participants (4.9%) had ideal 5-7 LS7 metrics. Over a mean follow-up of 14.2±7.9 years, 1162 individuals died, of which 315 were due to CVD. Age, sex, and ethnicity-adjusted HRs (95% CI) for all-cause mortality were 0.53 (0.41-0.68), 0.45 (0.34-0.59), 0.66 (0.49-0.87) and 0.75 (0.56-1.00) among those with ideal vs poor control of smoking, diet, physical activity and fasting blood glucose, respectively. However, the ideal and intermediate LS7 metrics were not significantly associated with lower risk of CVD mortality, except for a BMI between 25-29.9 kg/m. Those with 5-7 vs 0-1 ideal metrics had adjusted HRs 0.50 (0.40-0.87) for all-cause and 0.53 (0.21-1.36) for CVD mortality.

Conclusion: Ideal levels of multiple behavioral and health factors are associated with substantially lower risks for all-cause mortality, with a trend for lower CVD mortality among US adults with COPD.
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http://dx.doi.org/10.1016/j.resmer.2021.100860DOI Listing
November 2021

Awareness, diagnosis and treatment of heterozygous familial hypercholesterolemia (HeFH) - Results of a US national survey.

J Clin Lipidol 2021 Sep-Oct;15(5):682-689. Epub 2021 Sep 17.

Department of Cardiology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States (Karalis). Electronic address:

Background: HeFH is a common inherited disorder that leads to markedly elevated LDL-cholesterol from birth and premature cardiovascular disease. HeFH is frequently underdiagnosed and undertreated.

Objective: To compare how well primary care physicians and cardiologists recognize and treat HeFH.

Methods: The National Lipid Association surveyed 500 primary care physicians and 500 cardiologists in the US who have patients with baseline LDL-cholesterol ≥ 190 mg/dL. The survey was conducted between August 29 and September 30, 2019.

Results: For a hypothetical case of HeFH, 57% of cardiologists versus 43% of primary care physicians made the correct diagnosis (P<0.001). Among respondents, 21% of cardiologists versus 29% of primary care physicians have never made a diagnosis of HeFH in a patient with an LDL-cholesterol ≥ 190 mg/dL (P<0.004). Only 7% of cardiologists versus 5% of primary care physicians would refer to a lipid specialist (P=0.05). For additional LDL-cholesterol lowering after statins, 58% of cardiologists versus 48% of primary care physicians would prescribe a PCSK9 inhibitor (P=0.004); however, 30% of cardiologists versus 53% of primary care physicians have never prescribed a PSCK9 inhibitor in an HeFH patient (P<0.001).

Conclusion: Although cardiologists compared to primary care physicians are somewhat more likely to recognize and treat HeFH patients according to guidelines, both physician specialties do not adequately recognize or treat HeFH. There is a need for more education and training in recognizing and treating HeFH, greater access to lipid specialists, and fewer barriers for PCSK9 inhibitor use.
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http://dx.doi.org/10.1016/j.jacl.2021.09.045DOI Listing
March 2022

Editors' page for Sept 2021 issue.

Am J Prev Cardiol 2021 Sep 28;7:100228. Epub 2021 Jul 28.

Division of Cardiology, University of California Irvine, Irvine, CA, United States.

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http://dx.doi.org/10.1016/j.ajpc.2021.100228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361221PMC
September 2021

Identification and Predictors for Cardiovascular Disease Risk Equivalents among Adults With Diabetes Mellitus.

Diabetes Care 2021 Aug 11. Epub 2021 Aug 11.

Department of Epidemiology, University of California Los Angeles, Los Angeles, CA.

Objective: We examined diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors.

Research Design And Methods: We pooled 4 US cohorts (ARIC, JHS, MESA, FHS-Offspring) and classified subjects by baseline DM/CVD. CVD risks between DM+/CVD- vs. DM-/CVD+ were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD- vs. DM-/CVD+.

Results: The pooled cohort included 27,730 subjects (mean age of 58.5 years, 44.6% male). CVD rates per 1000 person-years were 16.5, 33.4, 43.2 and 71.4 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. Compared with those with DM-/CVD+, CVD risks were similar or higher for those with HbA1c ≥ 7%, diabetes duration ≥10 years, or diabetes medication use while those with less severe diabetes had lower risks. Hazard ratios (95%CI) for DM+/CVD- vs. DM-/CVD+ were 0.96(0.86-1.07), 0.97(0.88-1.07), 0.96(0.82-1.13), 1.18(0.98-1.41), 0.93(0.85-1.02) and 1.00(0.89-1.13) among women, white race, age <55 years, triglycerides ≥2.26 mmol/L, hs-CRP ≥ 2 mg/L and eGFR<60 mL/min/1.73m, respectively. In DM+/CVD- group, 19.1% had CVD risk equivalent diabetes with a lower risk score but a higher observed CVD risk.

Conclusion: Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, those of younger age, with higher triglycerides or CRP, or reduced kidney function.
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August 2021

Erratum to 'Lipid Treatment and Goal Attainment Characteristics among Persons with Atherosclerotic Cardiovascular Disease in the United States' [American Journal of Preventive Cardiology 1C (2020) 100010].

Am J Prev Cardiol 2021 Mar 29;5:100160. Epub 2021 Mar 29.

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, CA, USA.

[This corrects the article DOI: 10.1016/j.ajpc.2020.100010.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315635PMC
March 2021

When is it Appropriate to Lower Low Density Lipoprotein-Cholesterol Levels to <30 mg/dL?

Am J Cardiol 2021 10 1;157:142-144. Epub 2021 Aug 1.

Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, Oregon.

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October 2021

Editor's Message.

Am J Prev Cardiol 2021 Jun 8;6:100191. Epub 2021 May 8.

Division of Cardiology, University of California, Irvine, Irvine, CA 92697, United States.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315314PMC
June 2021

Response to the letter to the editor by Silverman-Lloyd et al. entitled: "Race is not a risk factor: Reframing discourse on racial health inequities in CVD prevention".

Am J Prev Cardiol 2021 Jun 10;6:100188. Epub 2021 Jun 10.

Heart Disease Prevention Program, Division of Cardiology, Department of Medicine, UC Irvine School of Medicine, University of California, Irvine, CA, United States.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315448PMC
June 2021

Editors' page - March 2021 issue.

Am J Prev Cardiol 2021 Mar 18;5:100162. Epub 2021 Feb 18.

Division of Cardiology, University of California Irvine, Irvine, California USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315330PMC
March 2021

Editors' page.

Am J Prev Cardiol 2020 Dec 1;4:100135. Epub 2020 Dec 1.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315313PMC
December 2020

Editors' Page.

Am J Prev Cardiol 2020 Sep 19;3:100092. Epub 2020 Oct 19.

University of California, Irvine, CA, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315597PMC
September 2020

Estimated ASCVD risk according to statin use in US adults with borderline triglycerides: Results from National Health and Nutrition Examination Survey (NHANES) 2007-2014.

Am J Prev Cardiol 2020 Sep 8;3:100087. Epub 2020 Sep 8.

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, USA.

Background: Elevated triglycerides (TGs) are associated with atherosclerotic cardiovascular disease (ASCVD). Despite statin therapy, many US adults have borderline or elevated TG levels. Not characterized is the ASCVD risk associated with borderline TG levels in statin users, including the estimated number of adults who will sustain ASCVD events.

Methods: We studied 4986 US adults (weighted to 113 million) aged 40-74 from the National Health and Nutrition Examination Surveys 2007-2014. The proportion of persons at low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), and high (≥20%) 10-year ASCVD risk among those on statins was quantified for low (<70 ​mg/dL, 70-<100 ​mg/dL), borderline (100-<135 ​mg/dL and 135-<150 ​mg/dL), borderline high (150-<200 ​mg/dL), and elevated (≥200 ​mg/dL) TGs. Multiple logistic regression examined these TG categories in relation to high risk status.

Results: Overall, 18.6% of participants had TG ​< ​70 ​mg/dL, 24.2% TG 70-<100 ​mg/dL, 22.0% TG 100-<135 ​mg/dL, 6.2% TG 135-<150 ​mg/dL, 15.0% TG 150-<200 ​mg/dL, and 14.0% TG ​≥ ​200 ​mg/dL. Mean 10-year ASCVD risk for these groups were 5.6%, 6.9%, 7.8%, 10.3%, 9.6% and 10.8%, respectively (p ​< ​0.0001). One-fifth or more of statin users with TGs over 135 ​mg/dL were at ≥ 20% 10-year ASCVD risk and ≥60% of persons in all TG groups were at borderline or higher ASCVD risk. Compared to those with TGs <70 ​mg/dL, multiple logistic regression showed odds ratios of 3.1 to 4.6 (p ​< ​0.05 to p ​< ​0.01) for those in TG groups ≥135 ​mg/dL in the overall sample, but 3.4 to 8.1 (p ​< ​0.05 to p < 0.01) for those in TG groups of ≥100 ​mg/dL in statin users, despite adjustment including HDL-C.

Conclusion: Many US adults with borderline levels of TGs are at elevated ASCVD risk despite statin therapy, suggesting the need first for greater lifestyle modification efforts, and when indicated, evidence-based therapies known to reduce this residual ASCVD risk.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315641PMC
September 2020

Cascade Screening and Treatment Initiation in Young Adults with Heterozygous Familial Hypercholesterolemia.

J Clin Med 2021 Jul 13;10(14). Epub 2021 Jul 13.

Department of Cardiology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.

Heterozygous familial hypercholesterolemia (HeFH) creates elevated low-density lipoprotein cholesterol (LDL-C), causing premature atherosclerotic cardiovascular disease (ASCVD). Guidelines recommend cascade screening relatives and starting statin therapy at 8-10 years old, but adherence to these recommendations is low. Our purpose was to measure self-reported physician practices for cascade screening and treatment initiation for HeFH using a survey of 500 primary care physicians and 500 cardiologists: 54% "always" cascade screen relatives of an individual with FH, but 68% would screen individuals with "strong family history of high cholesterol or premature ASCVD", and 74% would screen a child of a patient with HeFH. The most likely age respondents would start statins was 18-29 years, with few willing to prescribe to a pediatric male (17%) or female (14%). Physicians who reported previously diagnosing a patient with HeFH were more likely to prescribe to a pediatric patient with HeFH, either male (OR = 1.34, 95% CI = 0.99-1.81) or female (OR = 1.31, 95% CI = 0.99-1.72). Many physicians do not cascade screen and are less likely to screen individuals with family history of known HeFH compared to "high cholesterol or premature ASCVD". Most expressed willingness to screen pediatric patients, but few would start treatment at recommended ages. Further education is needed to improve diagnosis and treatment of HeFH.
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http://dx.doi.org/10.3390/jcm10143090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306062PMC
July 2021

Cardiovascular Outcomes with GLP-1 Receptor Agonists Versus SGLT-2 Inhibitors in Patients with Type 2 Diabetes.

Eur Heart J Cardiovasc Pharmacother 2021 Jul 2. Epub 2021 Jul 2.

Department of Cardiology and Clinical Research, Nordsjællands University Hospital, Hillerød, Denmark.

Aims: We examined cardiovascular outcomes associated with initiation of GLP-1RA versus SGLT-2i treatment in a real-world setting among patients with type 2 diabetes.

Methods And Results: This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8,913 new users of GLP-1RA and 5,275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was for the composite cardiovascular outcome, 5.6% (95% confidence interval (CI): 5.2-6.1) versus 5.6% (95% CI: 4.8-6.3); cardiovascular mortality, 1.6% (95% CI: 1.3-1.9) versus 1.5% (95% CI: 1.1-1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5-2.0) versus 1.8% (95% CI: 1.2-2.5); myocardial infarction, 2.1% (95% CI: 1.8-2.4) versus 2.1% (95% CI: 1.5-2.6); and stroke, 2.5% (95% CI: 2.2-2.9) versus 2.6% (95% CI: 2.2-3.1).

Conclusion: In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA versus SGLT-2i was not found to be associated with significant differences in cardiovascular risk.
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http://dx.doi.org/10.1093/ehjcvp/pvab053DOI Listing
July 2021

Impact of nutraceuticals on markers of systemic inflammation: Potential relevance to cardiovascular diseases - A position paper from the International Lipid Expert Panel (ILEP).

Prog Cardiovasc Dis 2021 Jul-Aug;67:40-52. Epub 2021 Jun 27.

Department of Hypertension, Medical University of Lodz (MUL), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. Electronic address:

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.pcad.2021.06.010DOI Listing
August 2021

Perceptions and Barriers on the Use of Proprotein Subtilisin/Kexin Type 9 Inhibitors in Heterozygous Familial Hypercholesterolemia (From a Survey of Primary Care Physicians and Cardiologists).

Am J Cardiol 2021 08 17;152:57-62. Epub 2021 Jun 17.

Division of Cardiology, Thomas Jefferson University Hospital. Philadelphia, PA.

Heterozygous familial hypercholesterolemia (HeFH) results in significant elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). Current guidelines recommend add-on proprotein subtilisin/kexin type 9 inhibitor (PCSK9i) therapy for additional LDL-C lowering beyond statins. Data are sparse, however, regarding treatment patterns and barriers relating to PCSK9i in HeFH patients. We examined physician attitudes, use, and barriers for treatment in patients with HeFH. We surveyed 1,000 physicians (500 primary care providers [PCPs] and 500 cardiologists in the US regarding their preferred treatments, experience and barriers associated with using PCSK9is. Cardiologists compared to PCPs were more likely to rank a PCSK9i as most important for an HeFH patient needing additional LDL-C lowering (68.6% vs. 64.8%; p <0.05), as well as prescribing and having a patient on a PCSK9i. PCPs vs. cardiologists were less likely (odds ratio [OR] [95% confidence interval] = 0.46 [0.34-0.63]), private vs. academic practice more likely (OR = 1.53 [1.02-2.28]), and those who would prescribe a PCSK9i in an HeFH patient with (OR = 3.86 [2.57-5.78]) or without (OR = 1.96 [1.40-2.72]) ASCVD needing additional LDL-C reduction beyond a statin were more likely to actually prescribe a PCSK9i. Those practicing in an urban vs. rural setting were less likely (OR = 0.56 [0.34-0.93]), and those indicating they would prescribe a PCKS9i in an HeFH patient with (OR = 2.80 [1.74-4.49]) or without (OR = 1.43 [1.02-2.02]) ASCVD needing additional LDL-C lowering beyond a statin were more likely to face difficulty prescribing a PCSK9i (all p <0.05 to p <0.01). Greater physician education and assistance among both cardiologists and PCPs are needed to address the gaps in understanding and treatment regarding PCSK9is.
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http://dx.doi.org/10.1016/j.amjcard.2021.04.034DOI Listing
August 2021
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