PREVENTIVE
CARDIOLOGY
Shaista Malik, MD, PhD, FACC
Associate Professor
Medical Director, Preventive Cardiology Program
Risk factor framework and the progression of cardiovascular disease, with types of
prevention interventions.
Franklin B A , and Cushman M Circulation. 2011;123:22742283
Copyright © American Heart Association, Inc. All rights reserved.
Concept of cardiovascular “risk factors”
Age, sex, hypertension, hyperlipidemia, smoking, diabetes,
(family history), (obesity)
Kannel et al, Ann Intern Med 1961
Framingham Heart Study: Kannel et al., 1961
ATP III Assessment of CHD Risk
For persons without known CHD, other forms of
atherosclerotic disease, or diabetes:
• Count the number of risk factors:
• Cigarette smoking
• Hypertension (BP 140/90 mmHg or on
antihypertensive medication)
• Low HDL cholesterol (<40 mg/dL)†
• Family history of premature CHD
• CHD in male first degree relative <55 years
• CHD in female first degree relative <65 years
• Age (men 45 years; women 55 years)
• Use Framingham scoring for persons with 2 risk factors* to
determine the absolute 10-year CHD risk. (downloadable risk
algorithms at www.nhlbi.nih.gov)
Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
www.lipidhealth.org
What’s New in the Cholesterol
Guideline?
1)Global Risk Assessment for Primary
Prevention
2)Focus on ASCVD reduction: 4 Statin Benefit
Groups
3)New Perspective on LDL-C Treatment Goals
4)Role of Biomarkers and Noninvasive Tests
High, Moderate and Low Intensity Statin Dosages
What are the Pooled Cohort Equations and
how do they differ from the Framingham Risk
Scores used before?
1) The new equations now predict 10-year risk of
both CHD and stroke (ASCVD) together rather
than just CHD which was the focus of the 2001
ATP III Framingham Risk Score recommended.
2) They predict nonfatal MI, CHD death, or nonfatal
or fatal stroke ONLY and do not include other
CVD (PCI, CABG, unstable angina requiring
hospitalization, PAD, etc.). Risk will be higher for
total CVD.
3) Available at www.cardiosource.org or
www.clincalc.com
Predicting ASCVD Risk?
Arterial
imaging/
function
Biomarkers
Metabolic syndrome
Family history
Pooled 10 yr ASCVD Risk Equation
Adapted from Kullo IJ, et al. Mayo Clin Proc. 2005;80:219-230.
54
PDAY study: US Adults 30-34 years of
age
Plaque Rupture: Majority less than 50% stenosis
ACC/AHA 2013 Cardiovascular Risk Assessment Working
Group Charge and Recommendations on Use of Other
Measures Beyond Global Risk Assessment Scoring
hs-CRP as a Risk Factor For Future CVD : Primary Prevention Cohorts
Kuller MRFIT 1996
Ridker PHS 1997
Ridker PHS 1997
CHD Death
MI
Stroke
Tracy CHS/RHPP 1997
CHD
Ridker PHS 1998,2001
PAD
Ridker WHS 1998,2000,2002
CVD
Koenig MONICA 1999 CHD
Roivainen HELSINKI 2000 CHD
Mendall CAERPHILLY 2000CHD
Danesh BRHS 2000
CHD
Gussekloo LEIDEN 2001
Fatal Stroke
Lowe SPEEDWELL 2001
CHD
Packard WOSCOPS 2001 CV Events*
Ridker AFCAPS 2001
Rost FHS 2001
CV Events*
Stroke
Pradhan WHI 2002
MI,CVD death
Albert PHS 2002
Sudden Death
Sakkinen HHS 2002
MI
0
Ridker PM. Circulation 2003;107:363-9
1.0 2.0 3.0 4.0 5.0 6.0
Relative Risk (upper vs lower quartile)
Coronary Calcium and Atherosclerosis:
Pathology Evidence
 Coronary calcium invariably
indicates the presence of
atherosclerosis, but
atherosclerotic lesions do not
always contain calcium (1-3).
 Calcium deposition may occur
early in life, as early as the second
decade, and in lesions that are not
advanced (4-5).
 Correlates with plaque burden;
highly sensitive for angiographic
disease
1) Wexler et al., Circ 1996; 94: 1175-92, 2) Blankenhorn and Stern, Am J Roentgenol 1959;
81: 772-7, 3) Blankenhorn and Stern, Am J Med Sci 1961; 42: 1-49, 4) Stary, Eur Heart J
1990; 11(suppl E): 3-19, 5) Stary, Arteriosclerosis 1989; 9 (suppl I): 19-32.
Cumulative Incidence of Any Coronary Event:
MESA Study
(Detrano et al., NEJM 2008)
Annual CHD Event Rates (in %) by Calcium Score Events by CAC Categories in
Subjects with DM, MetS, or Neither Disease
(Malik et al., Diabetes Care 2011)
Coronary Heart Disease
4
Annual
CHD
Event
Rate
4
3.5
3
2.5
2
1.5
1
0.5
0
3.5
1.9
1.5
0.4
0.8
0.2
0.1
0
2.1
0.4
1-99
2.2
1.3
DM
MetS
Neither MetS/DM
100-399
400+
Coronary Artery Calcium Score
ACCF/AHA 2010 Guideline: CAC Scoring for CV risk assessment in
asymptomatic adults aged 40 and over with diabetes (Class IIa-B)
CAC prognostic value on events in those at
extremes of risk factor burden
CAC has predictive value in those with 3
or more risk factors
CHD Risk in DM and MetS Depends on the Extent of
Subclinical Disease Present
(Malik and Wong et al., Diabetes Care 2011)
4
Annual
CHD
Event
Rate
4
3.5
3
2.5
2
1.5
1
0.5
0
3.5
1.9
1.5
0.4
0.8
0.2
0.1
0
2.1
0.4
1-99
2.2
1.3
DM
MetS
Neither MetS/DM
100-399
400+
Coronary Artery Calcium
Score
HR 6.2 (p<0.001) for CAC >=400 vs. 0 in predicting CHD
events
Prognostic value of CTA over CAC in
those with DM
Does coronary artery screening by electron beam CT
motivate potentially beneficial lifestyle behaviors?
“A Picture is Worth a Thousand Words”
In 703 men and women aged 28-84 who received scanning
for coronary calcium by EBCT, calcium score remained
independently associated with:
1) new aspirin usage
2) new cholesterol medication
3) consulting with a physician
4) losing weight
5) decreasing dietary fat
Potentially important risk-reducing behaviors may be
reinforced by the knowledge of a positive coronary
artery scan, independent of preexisting coronary risk
factor status. 1996 Dec 1;78(11):1220-3.
Wong ND et al, Am J Cardio, 1996
Prognostic value of CTA over CAC in
those with DM
Can Screening for Atherosclerosis Identify Those Most
Likely to Benefit from Lipid-Lowering Therapy?
Conclusions
• Good prediction does not necessarily lead to effective
•
•
•
•
•
prevention
Imaging markers of cardiovascular risk should be assessed by
their effect on patient management and outcomes
Effect of negative test on patient behavior and physician
management (warranty period, lifetime risk)
Personalization/individualized approach important in patients
with multiple risk factors/diabetes
Primary prevention strategies to prevent CVD in DM should be
based on the patient’s absolute risk of developing CVD events
rather than a blanket approach to treatment regardless of risk.
Broader view of health, lifestyle changes important for wellness
Conclusions
• LDL-C levels should still be used to guide adherence and
response to statin therapy
• New guidelines do not suggest the use of therapies added
to statins; however, ongoing clinical trials will provide
more guidance in this area.
• Clinical judgment should always be used when
considering therapy in areas where the guidelines do not
provide definitive advice.
• Referral to UCI Preventive Cardiology Clinic
• Nutritionist, Exercise Physiologist
• Advanced Biomarker Testing
• Advanced Imaging for detection of subclinical disease
CTA and behavior change
• CTRAD study
• 328 asymptomatic patients, no prior history of CAD, seen
in primary care clinics randomized to CTA vs. usual care
• Prelim results from subsample of those with diabetes
• Given a report of their findings with a grade signifying
amount of atherosclerosis
CTRAD study-patient reports
CTRAD study-patient reports
Changes in LDL after CTA-preliminary
data
LDL trend
102.00
100.00
98.00
99.53
98.07
97.15
LDL values
96.00
94.00
93.57
92.00
91.74
90.00
93.34
90.95
LDL_No SCAN
88.94
88.00
86.00
84.00
82.00
Baseline
M6
M18
LDL_SCAN
M36
Changes in A1c after CTA-preliminary
data
A1C trend
8.20
8.19
8.11
A1C values
8.00
7.97
7.96
7.98
7.98
7.82
7.80
A1C_SCAN
A1C_No SCAN
7.60
7.40
7.20
Baseline
M6
M18
M36
Coronary Artery Disease Detected by Coronary CT Angiography
Is Associated with Intensification of Preventive Medical Therapy
and Lower LDL Cholesterol
• 2839 patients without prior CAD who underwent CCTA from 2004 -
2011 and had complete data on medications before and after CCTA
were categorized as no CAD, <50% stenosis, and ≥ 50% stenosis.
• Extent of disease was categorized as non-extensive (≤4 segments) or
extensive CAD (>4 segments).
• Survival analysis was performed to evaluate intensification of lipid
therapy as a predictor of cardiovascular death or nonfatal myocardial
infarction (MI)
Hulten et al. Circ
Cardiovasc
Imaging. 2014 Jun
6 epub
Coronary Artery Disease Detected by Coronary CT Angiography
Is Associated with Intensification of Preventive Medical Therapy
and Lower LDL Cholesterol
• After follow-up of 3.6 years, the odds of physician intensification of
lipid lowering therapy significantly increased for those with nonobstructive CAD (OR 3.6, 95% CI 2.9 - 4.9, p < 0.001) and obstructive
CAD (OR 5.6, 95% CI 4.3 - 7.3, p<0.001).
• Low density lipoprotein (LDL) cholesterol levels declined significantly
in association with intensification of lipid lowering therapy after CCTA
in all patient subgroups.
Hulten et al. Circ
Cardiovasc Imaging. 2014
Jun 6 epub
Coronary Artery Disease Detected by Coronary CT Angiography
Is Associated with Intensification of Preventive Medical Therapy
and Lower LDL Cholesterol
Among patients with nonobstructive but extensive CAD,
statin use after CCTA was
associated
with a reduction in
cardiovascular death or MI (HR
0.18, 95% CI 0.05 – 0.66, p =
0.01).
Abnormal CCTA findings are associated with
downstream intensification in statin and aspirin
therapy. In particular, CCTA may lead to
increased use of preventive therapies in
patients identified as having extensive, non-
Hulten et al. Circ
Cardiovasc Imaging. 2014
Jun 6 epub
Beneficial Role of Coronary Multidetector CT Screening for
5-Year All-Cause Mortality among Asymptomatic DM
Patients
(H Kyung Yang et al., ADA 2014)
•
•
•
•
•
Asymptomatic T2DM subjects
774 received coronary MDCT and 1548 matched controls
did not get screened
Groups similar except longer duration DM and higher A1c
in screened group
After 31 month median follow-up, greater lipid decreases
and statin prescription in screened group
Coronary angiography and revascularization higher in
MDCT group
Beneficial Role of Coronary Multidetector CT Screening for 5Year All-Cause Mortality among Asymptomatic DM Patients
(Yang et al., ADA 2014)
• All cause mortality at 5 years lower in the MDCT
(4.5%) vs. non-MDCT (6.8%) group, p=0.02
• Authors conclude “MDCT may play a beneficial role
as a screening test to detect advanced macrovascular
complications in asymptomatic T2DM patients and to
increase survival rate”
Behavior Change and Moral Hazard: Implications of
negative screening tests or of preventive treatments
• RCT of diabetes screening
• Risk perception and changes
in smoking, physical activity,
body mass index (BMI), and
waist circumference were
compared between 706 highrisk participants with negative
test result and 706 high-risk
participants not offered
screening (controls).
• Negative-screened
individuals experienced a
small but significant increase
in BMI and waist
circumference compared to
positive screened individuals.
Willems et al, Ann Behav Med, 2014
New directions in Preventive Cardiology
• New lipid lowering agents
• PCSK9 Inhibitors
• Antisense Oligonucleotide (ASO) agents
Practical Approach to the New Cholesterol Guidelines
Pt> 21 yrs of Age
Screen for CV Risk Factors & Measure LDL
AtheroCVD
High
Dose
Statin
DM 1 OR 2
Age 40-75
LDL 70-189
No DM
Age 40-75
LDL 70-189
10 yr Risk
10 yr Risk
< 7.5%, Mod Dose Statin
>7.5%, High dose Statin
LDL> 190
High
Dose
Statin
>7.5% Mod-Hi Dose
No data for pts w/ Heart (NYHA 2-4); No benefit for dialysis pts
LDL =Low Density Lipoprotein mg/dL ( to convert to mmol/L, multiply by 0.0259)
AtheroCVD=Known atherosclerotic cardiovascular disease
A Pragmatic View of the New Cholesterol Treatment Guidelines Keaney et al November 27, 2013 NEJM