PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE FOR

PATIENTS WITH DIABETESBoback Ziaeian, MD PhD

Assistant Professor

Division of Cardiology

David Geffen School of Medicine at UCLA

VA Greater Los Angeles Healthcare System

@boback

EPIDEMIOLOGY

30.3 million Americans in 2015 with diabetes per CDC 12.2% of adults 23.1 M diagnosed 7.2 M undiagnosed

5.6 M with prevalent coronary heart disease in 2018

2.8 M prevalent stroke

2019 Primary Prevention Writing Committee

*ACC/AHA Representative, †Lay Representative, §Task Force Performance Measures Representative

Donna K. Arnett, PhD, MSPH, FAHA, Co-Chair

Roger S. Blumenthal, MD, FACC, FAHA, Co-ChairMichelle A. Albert, MD, MPH, FAHA* Erin D. Michos, MD, MHS, FACC, FAHA*Andrew B. Buroker, Esq† Michael D. Miedema, MD, MPH*Zachary D. Goldberger, MD, MS, FACC, FAHA‡ Daniel Muñoz, MD, MPA, FACC* Ellen J. Hahn, PhD, RN* Sidney C. Smith, Jr, MD, MACC, FAHA*Cheryl D. Himmelfarb, PhD, RN, ANP, FAHA* Salim S. Virani, MD, PhD, FACC, FAHA*Amit Khera, MD, MSc, FACC, FAHA* Kim A. Williams, Sr, MD, MACC, FAHA*Donald Lloyd-Jones, MD, SCM, FACC, FAHA* Joseph Yeboah, MD, MS, FACC, FAHA*J. William McEvoy, MBBCh, MEd, MHS* Boback Ziaeian, MD, PhD, FACC, FAHA§

Assessment of risk Nutrition and diet Exercise and physical activity

Overweight and obesity

Type 2 diabetes High blood cholesterol

High blood pressure and hypertension

Tobacco use Aspirin use

LIFESTYLE

The most important way to prevent atherosclerotic vascular disease, heart failure, and atrial fibrillation is to promote a healthy lifestyle throughout life.

LIFESTYLE

Avoiding toxic habits – high quality evidence for toxic exposures (i.e., tobacco, cocaine, methamphetamines)

Diet – observational, of questionable quality

Exercise – observational, of questionable quality

Generally not a controversial opinion, so no one applies the same standard of evidence/casual inference for Class I recommendations.

A team-based care approach is an effective strategy for the prevention of cardiovascular disease. Clinicians should evaluate the social determinants of health that affect individuals to inform treatment decisions.

TEAM-BASED CARE

Patient-Centered ApproachesRecommendations for Patient-Centered Approaches to Comprehensive

ASCVD Prevention

COR LOE Recommendations

I A

1. A team-based care approach is recommended for thecontrol of risk factors associated with ASCVD.

I B-R

2. Shared decision-making should guide discussions about the best strategies to reduce ASCVD risk.

I B-NR

3. Social determinants of health should inform optimal implementation of treatment recommendations for the prevention of ASCVD.

EXERCISE

22.90%

77.10%

Met recommended duration for both aerobic and muscle-strengthening activities

Metgoal

National Health Statistics Reports Number 112 June 28, 2018

Adults should engage in at least 150 minutes per week of accumulated moderate-intensity physical activity or 75 minutes per week of vigorous-intensity physical activity.

THE SPECTRUM OF PHYSICAL ACTIVITY

150 min of Mod-int/week75 min of vigor-int/week

300 min of Mod-int/week150 min of vigor-int/week

No more benefitHigher betterThe higher the better

NO LOWER LIMIT

MODERATE AND VIGOROUS INTENSITY EXERCISE

Treatment of T2DM for Primary Prevention of CVD

Aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit.

ASPIRIN FOR PRIMARY PREVENTION

Aspirin Use

Recommendations for Aspirin Use

COR LOE Recommendations

IIb A

1. Low-dose aspirin (75-100 mg orally daily) might beconsidered for the primary prevention of ASCVDamong select adults 40 to 70 years of age who are athigher ASCVD risk but not at increased bleeding risk.

III: Harm

B-R

2. Low-dose aspirin (75-100 mg orally daily) should notbe administered on a routine basis for the primaryprevention of ASCVD among adults >70 years of age.

III: Harm

C-LD

3. Low-dose aspirin (75-100 mg orally daily) should notbe administered for the primary prevention of ASCVDamong adults of any age who are at increased risk ofbleeding.

TRIALS OF ASPIRIN FOR PRIMARY PREVENTION

ASCEND ARRIVE ASPREE, 2018

15,480 with diabetes and no evident CVD.

12,546 with Moderate CVD risk w/o DM or high risk of GI bleeding

19,114 adults > 70 yr with no cardiovascular disease.

100 mg of aspirin vs. placebo 100 mg aspirin vs. placebo 100 mg aspirin vs. placebo

Reduction in vascular events was counterbalanced by bleeding

No difference in a composite of CV death, MI, UA, CVA, or TIA. With

increased risk of bleeding

Aspirin did not prolong disability free survival but increased major

hemorrhage

N Engl J Med. 2018;379:1529-39 Lancet. 2018;392:1036-46 N Engl J Med 2018; 379:1509-1518

ASPIRIN FOR ADULTS > 70 YEARS OF AGE: ASPREE

Cumulative Incidence of Major HemorrhageCumulative Incidence of Cardiovascular Disease

McNeil JJ, et al. N Engl J Med 2018; 379:1509-1518

Statin therapy is first-line treatment for primary prevention of ASCVD in patients with elevated low-density lipoprotein cholesterol levels (≥190 mg/dL), those with diabetes mellitus, who are 40 to 75 years of age, and those determined to be at sufficient ASCVD risk after a clinician–patient risk discussion.

STATINS

STATINS

Nonpharmacological interventions are recommended for all adults with elevated blood pressure or hypertension. For those requiring pharmacological therapy, the target blood pressure should generally be <130/80 mm Hg.

HYPERTENSION

HYPERTENSION

ACCORD

4,733 RCT

A1C ≥ 7.5%, CVD risk or disease

Intervention: SBP <120

Usual care: SBP <140

1° = MI, stroke, CVD death

~5 years of f/u

Event-rate 1.87% vs 2.09% (expected 4%), HR 0.88 (0.73-1.06, p=0.20)

SPRINT 9,361 RCT

Baseline SBP 130-180 mmHg

Additional cardiovascular risk factor, (hence PCE ≥ 10%

Intervention: SBP <120

Usual care: SBP <140

1° = MI, stroke, HF, ACS (-MI), stroke, CVD death

Median f/u 3.26 (stopped early)

1° Outcome: 1.65% vs. 2.19% per year, HR 0.75 (0.64-0.89, p<0.001)

All-cause mortality: HR 0.73; 0.60-0.90; P = 0.003

Figure 4. BP Threshds and Recommendations for Treatment

BP indicates blood pressure; and CVD, cardiovascular disease.

HYPERTENSION MANAGEMENT

LIMITATIONS OF ASCVD PCE CALCULATOR

Number of papers claiming over-estimation of risk. Problem with criticisms is incomplete event capture in other cohorts.

PCE included NIH cohort studies (ARIC, CHS, CARDIA, Framingham)

Revised PCE (ARIC, CHS, CARDIA, Framingham, JHS, MESA) used more modern statistical methods (elastic net regularization), only stratified by sex (not race).

With revised PC, less over-estimation of risk for AA on tails

https://sanjaybasu.shinyapps.io/ascvd/

PCE MAY UNDERESTIMATE RISK

HIV patients(Group 1:<5%, Group 2: 5%–7.5%, Group 3: >7.5%)

Circulation. 2018 May 22;137(21):2203-2214. Rheumatology (Oxford). 2017;56:1102-10.

RA patients (Black: observed events, Gray: predicted events)

PCE AND RISK ESTIMATION

PCE validated in non-Hispanic whites and non-Hispanic blacks living in the U.S.

Guidelines now have clear language about the limitations of the PCE“the PCE may overestimate or underestimate risk”

Not all factors are included in PCE:

Age SexRace Blood pressure Total cholesterolHDL cholesterolLDL cholesterolDiabetes SmokingHypertensionStatin therapy

Aspirin therapyFamily historyObesityPhysical inactivity Socioeconomic factorsPregnancy related CVD Inflammatory conditionsMental stress/ depression Chronic kidney diseaseMetabolic syndromeSouth Asian ethnicity

Elevated triglycerideshsCRPLp(a)ApoB levelAnkle-brachial indexCoronary artery calciumErectile dysfunction …

RISK-ENHANCING FACTORSTable 1. ASCVD risk enhancers

• Family history of premature ASCVD

• Primary hypercholesterolemia

• Chronic kidney disease

• Metabolic syndrome

• Conditions specific to women (e.g. preeclampsia, premature menopause)

• Chronic inflammatory conditions (especially rheumatoid arthritis, psoriasis, HIV)

• High risk race/ethnicity (e.g. South Asian ancestry)

Lipid/Biomarkers:

• Persistently elevated triglycerides (≥175 mg/dL)

In selected individuals if measured:

• hsCRP ≥2 mg/L

• Lp(a) levels ≥50 mg/dL or ≥125 nmol/L

• ApoB levels ≥130 mg/dL

• Ankle-brachial index <0.9

• Whom to use in?• Borderline (5% to <7.5%) or• Intermediate (≥7.5% to <20%) 10-year

ASCVD risk

• When to use?• Not cost-effective or evidence-based at

the population level.• If patient would value information in

making treatment recommendation.

• What to do if risk still uncertain?• CAC strong risk factor, but risk of

incidentalomas and excessive medical testing.

KNOW YOUR ABC’S