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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

Abstract

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.

Summary

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.

Keywords

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

Abbreviations

AACE

American Association of Clinical Endocrinologists

ACE

American College of Endocrinology

ACC

American College Cardiology

AHA

American Heart Association

ASCVD

Atherosclerotic cardiovascular disease

ACS

Acute coronary syndrome

ATP

Adult treatment panel

BP

Blood pressure

CAC

Coronary artery calcification

CAD

Coronary artery disease

CCTA

Coronary computed tomography angiography

CHD

Coronary heart disease

CHF

Congestive heart failure

CI 95%

Confidence interval

CKD

Chronic kidney disease

CVD

Cardiovascular disease

DM

Diabetes mellitus

eGFR

Estimated glomerular filtration rates

ESC

European Societies of Cardiology

EAS

European Atherosclerosis Society

FH

Familial Hypercholesterolemia

HeFH

Heterozygous familial hypercholesterolemia

HoFH

Homozygous familial hypercholesterolemia

HF

Heart failure

HR

Hazard ratio

HTN

Hypertension

HDL-C

High-density lipoprotein cholesterol

LDL-C

Low-density lipoprotein cholesterol

LVH

Left ventricular hypertrophy

MI

Myocardial infarction

MACE

Major adverse cardiovascular events

NCEP

National Cholesterol Education Program

NHLBI

National Heart, Lung, and Blood Institute

NLA

National Lipid Association

NF-MI

Non-fatal myocardial infarction

NNT

Number needed to treat

PAD

Peripheral artery disease

PCSK9

Proprotein convertase subtilisin/kexin type 9

PEP

Primary endpoint

RCTs

Randomized clinical trials

RR

Relative risk

T1DM

Type 1 diabetes mellitus

T2DM

Type 2 diabetes mellitus

TIA

Transient ischemic attack

TG

Triglycerides

UA

Unstable angina

Study Acronyms

4-D

Die Deutsche Diabetes Dialyse

AURORA

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

CORONA

Controlled Rosuvastatin Multinational Trial in Heart Failure

FOURIER

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

FHS

Framingham Heart Study

FOS

Framingham Offspring Study

GISSI-HF

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

GRACE

Global Registry of Acute Coronary Events

IMPROVE-IT

Improved Reduction of Outcomes: Vytorin Efficacy International Trial

MRFIT

Multiple Risk Factor Intervention Trial

OASIS

Organization to Assess Strategies for Ischemic Syndromes registry

ODYSSEY

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

PROVE-IT

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

REACH

Reduction of Atherothrombosis for Continued Health registry

REVERSAL

Reversal of Atherosclerosis with Aggressive Lipid Lowering trial

RUTHERFORD-2

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

SHARP

Study of Heart and Renal Protection

SHS

Strong Heart Study

TNT

Treating to New Targets

Notes

Acknowledgments

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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