CORONARY RISK FACTORS
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www.metcardio.org CORONARY RISK FACTORS Giuseppe Biondi Zoccai Giuseppe Biondi Zoccai Division of Cardiology, University of Turin, Turin, Italy Division of Cardiology, University of Turin, Turin, Italy Meta-analysis and Evidence-based medicine Training Meta-analysis and Evidence-based medicine Training in Cardiology (METCARDIO), Ospedaletti, Italy in Cardiology (METCARDIO), Ospedaletti, Italy
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CORONARY RISK FACTORS. Giuseppe Biondi Zoccai Division of Cardiology , University of Turin , Turin , Italy Meta-analysis and Evidence-based medicine Training in Cardiology (METCARDIO), Ospedaletti , Italy. LEARNING GOALS. Scope of the problem Established risk factors - PowerPoint PPT Presentation
Transcript of CORONARY RISK FACTORS
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CORONARY RISK FACTORS
Giuseppe Biondi ZoccaiGiuseppe Biondi Zoccai
Division of Cardiology, University of Turin, Turin, ItalyDivision of Cardiology, University of Turin, Turin, Italy
Meta-analysis and Evidence-based medicine Training in Meta-analysis and Evidence-based medicine Training in Cardiology (METCARDIO), Ospedaletti, ItalyCardiology (METCARDIO), Ospedaletti, Italy
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LEARNING GOALS
• Scope of the problem• Established risk factors• Risk factors still under investigation• So what?
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LEARNING GOALS
• Scope of the problem• Established risk factors• Risk factors still under investigation• So what?
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SCOPE OF THE PROBLEM
• Cardiovascular disease is the leading cause of mortality in developed countries
• Atherosclerosis is the main cause of cardiovascular disease
• Coronary atherosclerosis and atherothrombosis represent the single most important prognostic contributor to cardiovascular disease
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DEVELOPMENT OF ATHEROTHROMBOSIS
The 7 stages of development of an atherosclerotic plaque. First LDL moves into the subendothelium and is oxidized by macrophage
and SMCs (1 and 2). Release of growth factors and cytokines attracts additional monocytes (3 and 4). Foam cell accumulation
and SMC proliferation result in growth of the plaque (6, 7, and 8).Fuster, Circ 2004
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FROM ATHEROSCLEROSIS TO ATHEROTHROMBOSIS
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CORONARY ARTERY DISEASE3 out of every 10 individuals who develop
a heart attack or sudden death fromcoronary artery disease
have no prior warning or symptoms
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PREVENTION STRATEGIES• Primary prevention: strategies to reduce the
incidence of disease in apparently healthy subjects (e.g. vaccine)
• Secondary prevention: strategies to reduce the mortality and morbidity burden of disease once it has occurred (e.g. aspirin after AMI)
• Tertiary prevention: strategies to reduce the functional/symptomatic burden of disease after it has completed its natural history (e.g. wheel-chair training after stroke)
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No risk factors (i.e. low risk)
IMPACT AND ROLE OF PREVENTION OFATHEROTHROMBOSIS
Fuster, Circ 1999
SECONDARY PREVENTION
PRIMARYPREVENTION
One risk factor
Two or more risk factors
Subclinical atherosclerosis
Symptomatic non-coronary atherothrombosis
Symptomatic coronary athero-thrombosis
PA
TIE
NTS
AT
RIS
K
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RISK FACTORS AND GLOBAL DEATHS
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CAUSES OF DEATH IN EUROPE
MEN WOMEN
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RISK FACTORS IN ITALY
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ARE THERE ANY OUT OF THE BLUE MYOCARDIAL INFARCTIONS?
• 1 or more risk factor is present in 80-90% of patients with atherothrombosis
• Thus addressing established risk factors will potentially reduce by 80-90% the mortality and morbidity burden of atherothrombosis
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DISTRIBUTION OF RISK FACTORS AMONG PATIENTS WITH CAD
Khot et al, JAMA 2003
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CARDIOVASCULAR DISEASE
• Heart disease– Myocardial disease– Structural disease
• Vascular disease– Arterial disease– Venous disease– Pulmonary arterial disease– Pulmonary venous disease
Ischemic heart disease
≈Coronary heart
disease≈
Coronary artery disease
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ISCHEMIC HEART DISEASE• Silent coronary atherothrombosis
• Silent myocardial ischemia• Stable angina pectoris
• Ischemic cardiomyopathy• Unstable angina pectoris• Non-ST-elevation myocardial infarction
• ST-elevation myocardial infarction• Sudden ischemic cardiac death
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CORONARY RISK FACTORS: DEFINITION
• A coronary risk factor is a clinical or biologic feature associated in a clinically relevant fashion with increased (in some cases decreased) risk of coronary events
• Similarly, risk factors can be identified for any other condition/occurrence, e.g. cardiac events, coronary atherosclerosis, multivascular atherosclerosis, stroke, claudication, …
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LEARNING GOALS
• Scope of the problem• Established risk factors• Risk factors still under investigation• So what?
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METHODS OF INQUIRY
• EPIDEMIOLOGIC STUDIES – case-control or cohort studies
• PATHOLOGIC STUDIES – biopsy or autopsy• EXPERIMENTAL HUMAN STUDIES – randomized
clinical trials• EXPERIMENTAL ANIMAL STUDIES – mice, rats,
rabbits, pigs, dogs, monkeys
Each piece of evidence shares with the research study from which it stems strengths and weaknesses
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AN INCOMPLETE LISTUnmodifiable
Modifiable, established as independent
Modifiable, still under study
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AGE• Usually defined as:
–45 years or more for men–55 years or more for women without
premature menopause• Risk however is not discontinuous but
rather increases in a continuous, albeit non-linear, fashion
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FAMILY HISTORY• Myocardial infarction, coronary revascularization, sudden
ischemic or unexplained death before 55 years of age in father or other male 1st-degree relative (i.e., brother or son)
• Myocardial infarction, coronary revascularization, sudden ischemic or unexplained death before 65 years of age in mother or other female first-degree relative (i.e., sister or daughter)
• Family history of non-coronary atherothrombosis, diabetes, or hypertension, may also confer some, more limited, risk
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ARTERIAL HYPERTENSION
• Systolic blood pressure of ≥140 mmHg or diastolic ≥90 mmHg, confirmed by measurements on at least 2 separate occasions, or on antihypertensive medication
• Also risk factor for stroke, peripheral artery disease, and diastolic heart failure
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DYSLIPIDEMIA
• Total serum cholesterol of >200mg/dL (5.2 mmol/L) or high-density lipoprotein cholesterol of <35 mg/dL (0.9 mmol/L), or on lipid-lowering medication
• If low-density lipoprotein cholesterol is available, use >130 mg/dL (3.4 mmol/L) rather than total cholesterol of >200 mg/Dl
• Also risk factor for peripheral artery disease
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SMOKING
• Current cigarette smoker or those who quit within the previous 6 months
• Atherothrombotic risk usually approaches baseline risk after 3-5 years after quitting, but COPD does not
• Some risk is also conferred by cigars, pipes, and passive smoking
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SMOKING
Yusuf et al, Lancet 2004
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DIABETES MELLITUS• Diabetes mellitus is diagnosed if (any one):
– Fasting plasma glucose level at or above 126 mg/dL– Hemoglobin A1C at or above 6.5%– Plasma glucose at or above 200 mg/dL two hours after a 75 g
oral glucose load– Symptoms of hyperglycemia and casual plasma glucose at or
above 200 mg/dL• Given that the risk of CAD events in diabetics is similar to
the risk of recurrent CAD events in those with established CAD, diabetes is considered a coronary risk equivalent
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DIABETES MELLITUS: FROM INFLAMMATION TO ATHEROTHROMBOSIS
Biondi-Zoccai et al, JACC 2003
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ADDITIVE DETRIMENTAL EFFECTS OF RISK FACTORS
MRFIT
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ADDITIVE DETRIMENTAL EFFECTS OF RISK FACTORS
PANDORA
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ADDITIVE DETRIMENTAL EFFECTS OF RISK FACTORS
Yusuf et al, Lancet 2004
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LEARNING GOALS
• Scope of the problem• Established risk factors• Risk factors still under investigation• So what?
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AN INCOMPLETE LISTUnmodifiable
Modifiable, established as independent
Modifiable, still under study
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C-REACTIVE PROTEIN
Ridker et al, NEJM 2000
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C-REACTIVE PROTEIN
Ridker et al, NEJM 2002
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SOME OTHER NEW RISK FACTORS
Yusuf et al, Lancet 2004
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POPULATION ATTRIBUTABLE RISKS
Yusuf et al, Lancet 2004
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LEARNING GOALS
• Scope of the problem• Established risk factors• Risk factors still under investigation• So what?
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MASSIFIED VS PERSONALIZED CARE
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FROM DIAGNOSIS TO RISK-STRATIFICATION
• In as much as when interpreting the stress ECG or when admitting to the ER patients with suspected acute coronary syndromes, there has been a significant shift from diagnostic work-up to risk stratification
• Risk factors and scores prove seminal to achieve a successful prognostic work-up in most, albeit not all, individual patients
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RISK ASSESSMENT
Count major risk factors:
• For patients with multiple (2+) risk factors– Perform 10-year risk assessment
• For patients with 0–1 risk factor– 10 year risk assessment not required– Most patients have 10-year risk <10%
ATP III
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USING A CHECKLIST
Acharjee et al, AJC 2010
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THE FRAMINGHAM HEART STUDY
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THE FRAMINGHAM HEART STUDY
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BUILDING A RISK SCORE• Population at risk• Adjudication of events• Test for association between individual patient features
(e.g. gender) and incidence of events (e.g. % of death in males vs. females)
• Test to confirm association between several features and events, in order to adjust for covariates
• Calculation of adjusted odds ratios (or relative risks, or absolute risk) with 95% confidence intervals and area under the curve
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BUILDING A RISK SCORE• Population at risk• Adjudication of events• Test for association between individual patient features
(e.g. gender) and incidence of events (e.g. % of death in males vs. females)
• Test to confirm association between several features and events, in order to adjust for covariates
• Calculation of adjusted odds ratios (or relative risks, or absolute risk) with 95% confidence intervals and area under the curve
Final proof of causality is only obtained when a given intervention
effective at reducing a given risk factor leads to reduction in events
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GLOBAL ABSOLUTE CARDIOVASCULAR RISK
http://www.cuore.iss.it/valutazione/valutazione.asp
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http://www.cuore.iss.it/valutazione/valutazione.asp
GLOBAL ABSOLUTE CARDIOVASCULAR RISK
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http://www.cuore.iss.it/valutazione/valutazione.asp
GLOBAL ABSOLUTE CARDIOVASCULAR RISK
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NCEP/ATP III – 9 STEPS*• Step 1: Obtain, complete & fasting lipids• Interpret: LDL < 100mg/dl optimal LDL 100-129 near optimal LDL 130-159 borderline high LDL 160-189 high LDL >190 very high (mg/dl x 0.0259mmol/l = SI units)
*http://www.nhlbi.nih.gov/about/ncep/index.htm
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• Step 2: Identify if patient has CHD or equivalent (PAD, DM, AAA, Carotid)
• Step 3: Risk factor assessment• Step 4: If 2 or more risk factors; do Global
Cardiovascular Assolute Risk assessment
NCEP/ATP III – 9 STEPS*
*http://www.nhlbi.nih.gov/about/ncep/index.htm
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NCEP/ATP III – STEP 5*
Risk category LDL goal Start lifestyle changes
Start drug treatment
CHD/10yr risk>20%
(high)
<100mg/dl >100mg/dl >100 – 129mg/dl
2+RF or10yr<20%(Medium)
<130mg/dl >130mg/dl >130 – 160mg/dl
0-1 risk factors (low)
<160mg/dl >160mg/dl >160 – 190mg/dl
*http://www.nhlbi.nih.gov/about/ncep/index.htm
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NCEP/ATP III – STEP 6*
• Initiate therapeutic lifestyle changes (TLC) – Diet– Soluble fiber 10-25gm/day– Plant sterols/sitostanol– Increased exercise– Weight management
*http://www.nhlbi.nih.gov/about/ncep/index.htm
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NCEP/ATP III – STEP 7*• Add drug therapy simultaneously to TLC in
patients with CHD or equivalent. Add drugs after 3 months if TLC not effective in other risk categories:
Ezetimibe, Fibrates, Niacin,
PUFA, Resins, Statins *http://www.nhlbi.nih.gov/about/ncep/index.htm
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NCEP/ATP III – STEP 8*• Identify metabolic syndrome: (3 of 5)
– SBP>130, FBS>110, TG>150, HDL<40 in men and <50 in women, waist>40”men, 35”women
Aggressively:– Treat underlying causes of overweight and
physical inactivity.– Treat HTN, use ASA for CHD patients
*http://www.nhlbi.nih.gov/about/ncep/index.htm
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NCEP/ATP III – STEP 9*
• Treat elevated TG (>150mg/dl)– First lower LDL; if TG still >200 consider
adding/increasing drug therapy– But, if TG >500mg/dl, first lower triglycerides
to prevent pancreatitis. When they are <500 then return to LDL lowering
– Treat HDL <40 after lowering LDL.
*http://www.nhlbi.nih.gov/about/ncep/index.htm
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High RiskCHD or CHD risk
equivalents(10-yr risk >20%)
LDL-
C le
vel
100 -
160 -
130 -
190 -
Lower Risk
< 2 risk factors
Moderately High Risk
≥ 2 risk factors
(10-yr risk 10-20%)Target
160mg/dL
Target 130
mg/dL
70 -
Target 100
mg/dL
or optional
70 mg/dL*
Moderate Risk
≥ 2 risk factors(10-yr risk <10%)
Target 130
mg/dL
or optional
100 mg/dL**
Grundy SM et al. Circulation 2004;110:227-239.
MOST RECENT TARGETS
*Therapeutic option in very high-risk patients and in patients with high TG, non-HDL-C<100 mg/dL;**Therapeutic option; 70 mg/dL =1.8 mmol/L; 100 mg/dL = 2.6 mmol/L; 130 mg/dL = 3.4 mmol/L; 160 mg/dL = 4.1 mmol/L
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TAKE HOME MESSAGES
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TAKE HOME MESSAGES• Coronary risk factors represent a unique tool to risk
stratify subjects at risks and patients• Correction of risk factors reduces the incidence of
disease in apparently healthy subjects and the morbidity and mortality burden of atherothrombosis in patients with established disease
• An ongoing challenge is accomodating a massified approach to maximize compliance and universal benefits vs a personalized approach maximizing risk reduction and minimizing adverse effects
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Thank you for your attention
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