Primary Prevention of Coronary Artery Disease Raj Thaman Consultant Cardiologist Wrexham Maelor
Objectives Define primary prevention and discuss why primary prevention is necessary. review current approaches to primary prevention Discuss the limitations of the Framingham Risk Assessment model and others additional methods of refining risk stratification Review the evidence base for earlier and more aggressive treatment of hypercholesterolemia
Primary prevention of CVD Refers to interventions that aim to prevent or delay the onset of cardiovascular disease in people who have no clinical evidence of CVD (MeSH definition)
33% of deaths in the UK are caused by cardiovascular disease Men Causes of death in the UK Women CVD: cardiovascular disease; CHD: coronary heart disease Coronary Heart Disease Statistics, 2010. British Heart Foundation: London. http://www.bhf.org.uk/heart-health/statistics/mortality.aspx Last accessed August 2011.
There are regional variations in mortality from cardiovascular disease Deaths from CVD in the UK Males Females Regional variations exist in the incidence of CVD, with Scotland showing the highest rates for men and women CVD: cardiovascular disease Coronary Heart Disease Statistics, 2010. British Heart Foundation: London. http://www.bhf.org.uk/heart-health/statistics/mortality.aspx Last accessed August 2011.
What is responsible for reduction in mortality 50% of decline in CVD mortality is due to earlier diagnosis and more aggressive treatment 50%changes in risk factor profiles, decline in smoking, more aggressive management of BP and lipids
CVD (CHD, CVD, PVD) is the single most common cause of death in the UK Almost 30% (67,000) of the deaths can be classified as premature (that is, they occurred before the age of 75 years) (equates to 35% and 27% of all premature deaths in men and women) CVD is also a significant cause of morbidity and can have a major impact on quality of life. (In US it is estimated that the cost of treating coronary artery disease will rise to more than $1 trillion annually by 2030, thus prevention is needed)
Cardiovascular disease is associated with high healthcare costs Breakdown of healthcare costs associated with cardiovascular disease Medications 20% Primary care 6% Outpatient care 2% Accident and emergency care 0.5% Inpatient care 72% Cardiovascular disease cost the UK healthcare system approximately 14.4 billion in 2006 Adapted from Coronary Heart Disease Statistics, 2010. British Heart Foundation: London. http://www.bhf.org.uk/heart-health/statistics/economic-costs-of-cvd.aspx Last accessed August 2011.
Primary prevention of CHD The fundamental principle in primary prevention of Coronary Heart Disease is the identification of individuals with coronary risk factors and modify those risk factors
Modifiable factors increase the risk of myocardial infarction (MI) Abnormal lipids Diabetes Abdominal obesity Inadequate consumption of fruit and vegetables Lack of regular physical exercise Smoking Hypertension Psychosocial factors Excess alcohol Case control study of acute MI in 52 countries Nine risk factors account for >90% of the population attributable risk of MI MI: myocardial infarction Yusuf S, et al. Lancet. 2004; 364:937 952.
Abnormal lipids and current smoking status are associated with the highest risk of developing acute myocardial infarction Odds ratios for risk factors most associated with the development of acute myocardial infarction *Lipid profile as measured by apolipoprotein B/apolipoprotein A1 ratio Adapted from Yusuf S, et al. Lancet. 2004; 364: 937 952.
Cumulative incidence of CVD adjusted for the competing risk of death for men and women according to aggregate risk factor (RF) burden at 50 years of age IDEAL RISK FACTOR PROFILE BP 120/80 CHOL <180 NONSMOKER NON DIABETIC Lloyd-Jones, D. M. et al. Circulation 2006;113:791-798
Rationale Primary prevention reduces MI and HF, decreases the need for coronary revascularization procedures, and extends and improves QOL Treating hypercholesterolaemia in patients who do have evidence of CHD
Principles For primary prevention of cardiovascular disease (CVD), people at risk need to be identified before CVD has become established To assess risk in those likely to be at high risk (for example, people with hypertension) a validated assessment tool is needed that evaluates a range of modifiable and non-modifiable risk factors. Epidaemiological data showing that there is a continuous graded relationship between the total plasma cholesterol concentration and CHD events and mortality
Risk Stratification Calculators Framingham Joint British Societies Q Risk ASSIGN (Scotland only)
Framingham Major risk factors in asymptomatic individuals: smoking, hypertension, high cholesterol (and various cholesterol fractions). Low HDL, diabetes and age Major RF s (85% of excess risk Obesity, physical inactivity, family history of premature CHD, hypertriglycideaemia, small LDL, increased lipoprotein a, increased serum homocysteine and abnormalities in several coagulation factors (fibrinogen), Insulin resistance
Framingham Cardiovascular Risk Calculator For Primary Prevention This calculator should not be used if patient has known CVD or diabetes (already known to be at high risk) Age (30-74) Sex Smoking Status Glucose (normal, impaired, diabetic) Systolic BP LVH on ECG yes/ no Diastolic BP Central Obesity yes/ no Total Cholesterol South Asian Origin yes/ no HDL Cholesterol Family History of CVD (Men ) Total /HDL Ratio Serum TG mmol/l 10-year risk of cardiovascular event is. % Values used should have been recorded <6 months before the date of the risk assessment and before any treatment for hypertension. adjustments as suggested by the Joint British Societies' (JBS2) paper and the JBS Cardiovascular Risk Assessor
Advantage of Framingham Risk Estimate: allows calculations over various time periods (4 to 12 years) and for different outcomes: cardiovascular disease, stroke, coronary disease, myocardial infarction and death from either coronary or cardiovascular disease
Limitations of Framingham Risk Estimate Age and gender are the predominant factors in risk estimate Life time risk estimate may be more relevant than 10 year estimate Over-estimate risk in low risk populations Overestimates risk in high risk populations (upt o 50%). should not be used in people with pre-existing CVD (coronary heart disease, angina, stroke, TIA, PVD,diabetes, CKD (if estimated GFR < below 60), familial hypercholesterolemia, or in people already taking lipid- lowering medication before a new diagnosis of hypertension Guidelines emphasize coronary event reduction rather than preventing atherosclerosis
Joint British Societies (JBS) Published in the BNF and based on JBS guidelines. Based on Framingham data JBS/BNF calculates cardiovascular disease risk, based on the sum of the coronary disease and stroke risks (i.e. not individualised).
Q risk 2010: NICE decided it could no longer recommend that the Framingham risk equation be the equation of choice [NICE clinical guideline 67 (reissued in February 2010) ] coincided with the emergence of the QRISK calculator which has been shown to predict risk more accurately The QRISK cardiovascular calculator calculates lifetime risk validated using data from a UK primary care database.
Age Sex male/ female Ethnicity Postcode About You Clinical Information Do you smoke at all? Do you have diabetes? Are you on regular steroid tablets? Do you have high blood pressure requiring treatment? Have you had a heart attack, angina, stroke or TIA Has anyone in your immediate family* had angina or a heart attack whilst under 60 Do immediate family* have diabetes? Have you been diagnosed with rheumatoid arthritis? Have you been diagnosed with chronic kidney disease? Have you been diagnosed with atrial fibrillation or irregular heartbeat? Do you have congestive cardiac failure? Do you have hypothyroidism? Do you have liver failure? Cholesterol/HDL ratio: Systolic blood pressure (mmhg): Body mass index Weight (kg):height (cm): Calculate
Advantages of Q risk More personalized More risk factors: rh art, AF, renal disease, treated hypertension Takes into account your postcode, areas of deprivation Other ethnic variables At the 10year risk threshold of 20%,the population identified by QRISK2 was at higher risk of a CV event than the population identified by the modified algorithm
Are scoring algorithms accurate Risk factors change with age What is the impact of those emerging risk factors or others such as childhood obesity Low absolute risk does not mean low lifetime risk Scores don t take into account severity of risk factors (heavy smoking, marked hypertension) Patients aged over 75 years?? Secondary prevention Most scoring systems underestimate risk
Effect of individual RF s on Atherogenesis Each of major RF s Smoking, BP
Clinical effectiveness of primary prevention Nurses Health study: 120,000, 20 yrs, women who maintained a desirable body weight, ate healthy diet, exercised regularly, and didn t smoke had an 84% reduction in CVD events (3-5% low risk). Meta analysis of PP trials (including a minority of people with established CVD), found that statin therapy was associated with a reduction in the risk of all cause mortality, fatal and nonfatal MI and the composite outcomes of CHD death, nonfatal MI, fatal or nonfatal stroke and coronary revascularization
Study Year Primary prevention trials Number Mean Age M/F LDL Event Reduction MI/CV Death WOSCOPS 1995 Pravastatin AFCAPS/ TEXCAPS 1998 Lovastatin 6595 55 M 190 140 6605 58 85/15 150 112 31% (5 years) 37% (5 years) ASCOT 2003 Atorvastatin 10305 63 80/20 132 85 Independent of other predictors of outcome 36% Meta analysis of PP trials (including a minority of people with established CVD), found that statin therapy was associated with a reduction in the risk of all cause mortality, fatal and nonfatal MI and the composite outcomes of CHD death, nonfatal MI, fatal or nonfatal stroke and coronary
Are statins effective over a wide range of LDL-C Study population (n=17,802) No history of cardiovascular disease LDL cholesterol < 3.4 mmol/l C-reactive protein (CRP) 2 mg/l Men 50 years Women 60 years Rosuvastatin 20 mg (n=8,901) Placebo (n=8,901) 1 6 2 4 3 0 4 13 6 monthly Final 3 4 years Run in/eligibility Safety Lipids CRP Safety Median follow-up: 1.9 years Lipids CRP Safety Lipids CRP Safety HbA 1C JUPITER Ridker PM et al. Circulation. 2003; 108: 2292 2297. Ridker PM et al. Am J Cardiol. 2007; 100: 1659 1664.
JUPITER: post-hoc analysis of high-risk subgroup baseline Framingham risk score >20% Cumulative incidence of cardiovascular death/myocardial infarction/stroke Cumulative incidence, % 10 9 8 7 6 5 4 3 2 1 Hazard ratio: 0.50 (95% CI: 0.227-0.93) P = 0.028 NNT 4y = 26 Placebo Rosuvastatin 0 0 1 2 3 4 5 Rosuvastatin 749 359 Years 131 63 24 Placebo 717 335 110 43 14 Koenig W, Ridker PM. Eur Heart J. 2011; 32: 75 83.
JUPITER: post-hoc analysis of high-risk subgroup baseline Framingham risk score >20% In patients with a baseline Framingham risk score >20% (n=1558 patients), there was: A significant reduction in the combined end-point of cardiovascular death, stroke and myocardial infarction (hazard ratio: 0.5; p=0.028 rosuvastatin vs. placebo) Absolute risk reduction (ARR) in the event rate per 1000 patient-years was 8.8 Total mortality was unchanged (p=0.193) Koenig W, Ridker PM. Eur Heart J. 2011; 32: 75 83. Crestor. Summary of Product Characteristics. February 2011.
Which patients should we intervene on Elevated total cholesterol to HDL cholesterol ratio 6.0 Elevated blood pressure Evidence of atherosclerotic disease All patients Diabetes mellitus and aged over 40 years Diabetes mellitus aged under 40 years and additional risk factors Smoking status Obesity HDL: high density lipoprotein JBS 2. Heart 2005; 91(suppl V): v1-v52. Many factors contribute to cardiovascular risk
Risk Catergories Who should receive cardioprotective drugs low: Modify risk (<10%) Cost effectiveness models have not shown benefit of treating low risk patients with generic low intensity statins once adherenace is taken into account Intermediate:??? High: 20% ----- cardioprotective drugs Invasive investigations
NICE recommends that patients at risk of cardiovascular events are regularly screened If the person has a history of CHD, angina, stroke or TIA, peripheral vascular disease, diabetes or a monogenic lipid disorder, do not include in risk assessment process as these patients are already considered at high risk Is person 75 or over? Use systematic strategy rather than opportunistic assessment to identify people aged 40 74 who are likely to be at high risk No Yes Consider at increased risk of CVD, and likely to benefit from statin treatment, particularly if person smokes or has high blood pressure. Consider comorbidities, benefits and risks of treatment, and person s preference Estimate risk using risk factors already recorded in primary care electronic medical records 10-YEAR RISK LESS THAN 20% 10-YEAR RISK 20% OR GREATER Prioritise for full format risk assessment Arrange discussion of risk assessment Review risk on an ongoing basis Discuss process of risk assessment, including option to decline assessment RISK ASSESSMENT DECLINED CHD: coronary heart disease; TIA: transient ischaemic attack; CVD: cardiovascular disease The National Collaborating Centre for Primary Care. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. CG67. Quick reference guide. June 2008. Available at: http://guidance.nice.org.uk/cg67/quickrefguide/pdf/english Last accessed August 2011.
JBS cont (I) OBJECTIVE OF CVD PREVENTION IN CLINICAL PRACTICE is to reduce the risk of CVD and its complications, including the need for percutaneous or surgical revascularisation procedures in any arterial territory, and to improve quality of life and life expectancy. (II) PRIORITIES FOR CVD PREVENTION IN CLINICAL PRACTICE CVD prevention should focus on all those people who are at high risk, and the following groups of people have equal priority for CVD prevention in clinical practice. People with any form of established atherosclerotic CVD Asymptomatic people without established CVD but who have a combination of risk factors which puts them at high total risk (estimated multifactorial CVD risk 20% over 10 years) of developing atherosclerotic CVD for the first time People with diabetes mellitus (type 1 or 2) In addition, other people with particularly elevated single risk factors also require CVD prevention because they too are at high cardiovascular risk, regardless of the presence of other risk factors: elevated blood pressure 160 mm Hg systolic or 100 mm Hg diastolic, or lesser degrees of blood pressure elevation with target organ damage elevated total cholesterol to high density lipoprotein (HDL) cholesterol ratio 6.0 familial dyslipidaemia People with a family history of premature CVD should be assessed and then managed appropriately
Problems with this approach The goal for reducing elevated serum cholesterol in adults is to retard atherogenesis throughout life, not to prevent myocardial infarction in the next decade Reduction of serum cholesterol levels in patients with advanced atherosclerotic disease does not substantially reduce mortality and morbidity from CHD High risk cohorts will have overall relatively few events, most events will occur in those patients at intermediate risk.
Can we detect atherogenesis Calcification occurs in most atheroscerotic plaques sub-intimal space Total CAC proportional to total plaque area (CAC makes up about 15-20% of total plaque area) Coronary angiography: luminography Using CT CAC can be visualised within a few seconds at a low radiation exposure
Quantification of CAC Agatston score (Agatston et al 1990) If there is no CAC can rule out obstructive CAD (0.5%) Acute coronary events can occur in patients with no detectable CAC, eg young smokers Independent risk factor for CV events (park et al 2002) The higher the CAC score the greater the likelihood of MI or cardiovascular death. Independent of CV risk factors (Arad et al) Sensitivity 98% Spec 40% PPV 68% NPP 93% A score >100 more predictive of CV event than traditional RF s
Who should be screened with CTCS Asymptomatic patients low risk patients: very few events are expected in these patients so CAC is unlikely to reclassify patients Most high risk patients will remain high risk even with a relatively low CAC score. Intermediate risk patients are more likely to be reclassified In these patients a score >100 would reclassify them as high risk
Use of CCS scoring Male>40 years Female >50 years Framingham/ JBS/ Q Risk assessment Low (<10%) Intermediate (10%-20%) High (>20%) Life style modification CCS Scoring Secondary prevention Absent CAC Any CAC
Summary Primary prevention is extremely important, clinical and cost implications Patients should be risk stratified whenever possible Risk calculators have their limitations Statins in primary prevention are associated with substantial relative reductions in cardiovascular events Newer technologies may help refine risk stratification in the future