Current Diabetes Reports

, 19:61 | Cite as

Extreme Atherosclerotic Cardiovascular Disease (ASCVD) Risk Recognition

  • Paul D. RosenblitEmail author
Macrovascular Complications in Diabetes (VR Aroda and A Getaneh, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Macrovascular Complications in Diabetes


Purpose of Review

To distinguish extreme and very high atherosclerotic cardiovascular disease (ASCVD) event risk based on prospective epidemiological studies and clinical trial results.

Recent Findings

Clinical practice guidelines have categorized patients with either a history of one or more “clinical ASCVD” events or “coronary heart disease (CHD) risk equivalency” to be at “very high risk” for a recurrence or a first event, respectively. A 20% or greater 10-year ASCVD risk for a composite 3-point “major” atherosclerotic cardiovascular event (MACE) of non-fatal myocardial infarction (MI), non-fatal stroke, or cardiovascular death can serve as an arbitrary definition of those at “very high risk.” Exclusion of stroke may underestimate risk of “hard” endpoint 10-year ASCVD risk and addition of other potential endpoints, e.g., hospital admission for unstable angina or revascularization, a 5-point composite MACE, may overinflate the risk definitions and categorization. “Extreme” risk, a descriptor for even higher morbidity and mortality potential, defines a 30% or greater 10-year 3-point MACE (ASCVD) risk. In prospective, epidemiological studies and randomized clinical trial (RCT) participants with an initial acute coronary syndrome (ACS) within several months of entry into the study meet the inclusion criteria assignment for extreme risk. In survivors beyond the first year of an ASCVD event, “extreme” risk persists when one or more comorbidities are present, including diabetes, heart failure (HF), stage 3 or higher chronic kidney disease (CKD), familial hypercholesterolemia (FH), and poorly controlled major risk factors such as hypertension and persistent tobaccoism. “Extreme” risk particularly applies to those with progressive or multiple clinical ASCVD events in the same artery, same arterial bed, or polyvascular sites, including unstable angina and transient ischemic events. Identifying asymptomatic individuals with extensive subclinical ASCVD at “extreme” risk is a challenge, as risk engine assessment may not be adequate; individuals with genetic FH or those with diabetes and Agatston coronary artery calcification (CAC) scores greater than 1000 exemplify such threatening settings and opportunities for aggressive primary prevention.


Heterogeneity exists among individuals at risk for clinical ASCVD events; identifying those at “extreme” risk, a more ominous ASCVD category, associated with greater morbidity and mortality, should prompt the most effective global cardiometabolic risk reduction.


Atherosclerotic cardiovascular disease (ASCVD) Major atherosclerotic cardiovascular risk (MACE) Extreme risk Very high risk Multi-morbidities Secondary prevention 



American Association of Clinical Endocrinologists


American College of Endocrinology


American College Cardiology


American Heart Association


Atherosclerotic cardiovascular disease


Acute coronary syndrome


Adult treatment panel


Blood pressure


Coronary artery calcification


Coronary artery disease


Coronary computed tomography angiography


Coronary heart disease


Congestive heart failure

CI 95%

Confidence interval


Chronic kidney disease


Cardiovascular disease


Diabetes mellitus


Estimated glomerular filtration rates


European Societies of Cardiology


European Atherosclerosis Society


Familial Hypercholesterolemia


Heterozygous familial hypercholesterolemia


Homozygous familial hypercholesterolemia


Heart failure


Hazard ratio




High-density lipoprotein cholesterol


Low-density lipoprotein cholesterol


Left ventricular hypertrophy


Myocardial infarction


Major adverse cardiovascular events


National Cholesterol Education Program


National Heart, Lung, and Blood Institute


National Lipid Association


Non-fatal myocardial infarction


Number needed to treat


Peripheral artery disease


Proprotein convertase subtilisin/kexin type 9


Primary endpoint


Randomized clinical trials


Relative risk


Type 1 diabetes mellitus


Type 2 diabetes mellitus


Transient ischemic attack




Unstable angina

Study Acronyms


Die Deutsche Diabetes Dialyse


A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events


Controlled Rosuvastatin Multinational Trial in Heart Failure


Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk


Framingham Heart Study


Framingham Offspring Study


Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Heart Failure Study


Global Registry of Acute Coronary Events


Improved Reduction of Outcomes: Vytorin Efficacy International Trial


Multiple Risk Factor Intervention Trial


Organization to Assess Strategies for Ischemic Syndromes registry


Outcomes Trial to determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS


Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) trial


Reduction of Atherothrombosis for Continued Health registry


Reversal of Atherosclerosis with Aggressive Lipid Lowering trial


Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2


Study of Heart and Renal Protection


Strong Heart Study


Treating to New Targets



The author would like to thank Dr. Asqual Getaneh for critical review, feedback, and edits of earlier and current drafts of this review.

Compliance with Ethical Standards

Conflict of Interest

12-month 1/1/18-12/31/18 disclosure

Paul D. Rosenblit received clinical trial research site funding from Amgen, AstraZeneca, Dexcom, GlaxoSmithKline, Ionis, Mylan, and Novo Nordisk. He received speaker faculty honoraria from Akcea, Amgen, Merck, and Novo Nordisk. He received advisory board honoraria from Akcea, Esperion, and Novo Nordisk.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department Medicine, Division Endocrinology, Diabetes, MetabolismUniversity California, Irvine (UCI), School of MedicineIrvineUSA
  2. 2.Diabetes Out-Patient ClinicUCI Medical CenterOrangeUSA
  3. 3.Diabetes/Lipid Management & Research CenterHuntington BeachUSA

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