CT Calcium Score and Statins in Primary CV Prevention. Dr Selwyn Wong
Promises, Pitfalls and Hard Truths of Coronary Calcium Scanning Selwyn Wong Ascot and Middlemore Hospitals
Coronary Calcium Scoring CTscan - non-contrast ECG-gated Negligible radiation 1mSv (annual background radiation is 3 msv) Agatson score quantifies calcium (volume and density) Coronary calcification increase with age Reports - absolute score + percentile band Reported score; 0, 1-100, 101-300, >310
Coronary Calcium Scoring
Coronary Calcium Scoring
Predicted 7-year risk of CHD% South Bay Heart Watch Study 20 1312 Men >45yo with 1 Coronary Risk Factor 16 12 0 0-1 0 0 101-300 > 300 p=0.006 p<0.001 8 p<0.001 p=0.21 4 0 0-9 10-1 5 16-2 0 > 2 0 Greenland P et al. JAMA 2004;291:210-215
Cumulative Incidence Major CV Events (%) CAC and Coronary Events: The MESA Study AUC Coronary artery calcium score RF RF + CAC 0.79 0.83 HR CAC >300 = 9.7 (5.2-18) Any Coronary Event Years to Event Detrano R et al. NEJM 2008;358:1336
Cardiovascular Risk Assessment CAC is a marker of atherosclerosis Framingham-based on major traditional RF Typical classification to low/intermediate/ high-risk but deficiences NZ Heart Forecast/Predict do include FHx CCS provides additive information for risk-assessment
Risk Metrics of CAC Scanning in Recent Population Based Studies Adj HR CHD 400(300) vs. 0 NRI NRI (Intermediate Risk) Δ C-stat MESA (n=6814) HNR (n=4129) Rotterdam (n=2028) 9.7 25% 55% + 6.0 24% 31% + 4.6 14% 52% + Polonsky T. et al. JAMA 2010;303:1610; Erbel et al. J Am Coll Cardiol 2010; 567 1455 Mohlenkamp et al. J Am Coll Cardiol 2011; 57:1455 Vliegenthart et al. Circ 2005; 112:572 Elias-Smale et al. J Am Coll Cardiol 2010;56:1407
Comparison of Risk Reclassification and Discrimination of Novel Tests NRI NRI (Intermediate Risk) Δ C-stat Study CAC 14%-25% 31%-55% + HNR, Rotterdam, MESA Carotid IMT 7.6%-9.9% 21% + FHS, ARIC CRP 1.5%-5.7% 15% -/+ ERC, WHS Polonsky T. et al. JAMA 2010;303:1610; Erbel et al. J Am Coll Cardiol 2010; 56: 1397 Elias-Smale et al. J Am Coll Cardiol 2010;56:1407; Nambi V. et al. JACC 2010;55:1600; Polak J. et al. NEJM 2011;365:213; ERC. NEJM 2012;367:1310; Cook NR. Stat Med 2008; 27:191
Probability of survival Very Low Event Rates in Asymptomatic Individuals with CAC=0 Meta-analysis 71,595 Subjects n=44,052 CV CAC=0 Event ~0.1% CAC>0 Rate/yr ~1% Blaha M et al. JACC Imag. 2009;2:692-700 Sarwar A et al. JACC Imag. 2009;2:675-688
Predicted 7-year risk of CHD% South Bay Heart Watch Study Events in Those with CAC=0 20 Event Rate 0% 2.5% 4.3% 9.3% N 46 79 116 75 16 12 0 0-1 00 101-3 00 > 300 p=0.006 p<0.001 8 4 p=0.21 p<0.001 0 0-9 10-1 5 16-2 0 > 2 0 Greenland P et al. JAMA 2004;291:210-215
IIA ACC/AHA CV Risk Assessment Guidelines 2010 CAC, intermediate risk (10% to 20%10-year risk) (Level of Evidence: B) IIB CAC, intermediate risk (6% to 10% 10-year risk) (Level of Evidence: B) III CAC, low risk (<6% 10-year risk) (Level of Evidence: B) Greenland et al JACC 2010;56:2182-2199
16% FRS Categories in Adults: NHANES 1999-2002 Men 11% 4% Women 20% <10% 10-20% >20% 65% <10% 10-20% >20% Ajani U and Ford ES. JACC 2006;48:1177-82 86%
% in Low Risk Group % in Low Risk Group 100% Significant Proportion of CAC in Low Risk Subjects: Dallas Heart Study Men 30-65 (n=1161) 100% Women 30-65 (n=1449) 80% 80% 72% 60% 60% 40% 20% 30% 27% 40% 20% 24% 0% CAC 100-399 CAC 400 0% CAC 100-399 CAC 400 Patel MJ et al. AHJ 2009;157:1001-1009
Family History, CAC, and CHD Events: Dallas Heart Study Paixao A. ACC 2013
Treatment Effects of CCS 1 small observational study and 1 small randomised study outcome CAC progression No outcomes data for prevention strategy using CAC scores
CCS Benefit on Compliance and Resources Mixed data Cost-effectiveness not defined
Conclusions Simple low risk test Zero scores are associated with markedly low risk of CHD events CCS enhances FRS predictive value -current best novel test. No integrated calculator A meaningful number of low risk individuals have significant CAC, but event rate is low
Conclusions No outcome data hence treatment effect unknown Effect of false-positive result and radiation exposure unknown Compliance benefit uncertain Cost-effectiveness not defined
Conclusions CAC score for INTERMEDIATE RISK if result/reclassification will alter management CAC score NOT for high-risk or (most) low-risk patients
Case 4 -Aspirin, Vitamin supplements and Antioxidants in Primary CV Prevention New patient 65 year Caucasian male with several questions;..a close friend has recently dropped dead of a heart attack.what can I do to avoid the same fate??
Case 4 - History Sedentary. Breathless up slopes?older. Anxious about increasing exercise. Non-smoker, no Hx HTN or DM. Lipids unknown. Father with CABG age 72
Case 4 Risk Assessment BP - 125/80mmHg Father CABG 72years age No DM HbA1C 35mmol/mol Non-smoker Total cholesterol 5.1mmol/L, HDL 1.0mmol/L, Triglycerides 1.8mmol/L, LDL 3.9mmol/L, ratio 5.1. Height 1.75m, weight 89kg, BMI 29, waist 100cm, hips 92cm.
Case 4 Risk Assessment
Case 4 Risk Assessment
Case 4 Risk Assessment
Case 4 Risk Assessment
Case 4 Risk Assessment
Case 4 Risk Assessment
Case 4 Risk Assessment
Case 4 Risk Assessment Now what in terms of tests and treatment for risk reduction?
Case 4 Clinical Assessment
Further tests CCS, Lp(a), hscrp bleeding. Decisions about aspirin use should be made by balancing the risks against the benefits in the context of each individual's medical history, and any decision should be made only in consultation with a healthcare professional Case 4 Treatment Options Statin Class IA evidence in primary prevention Aspirin - recent evidence about aspirin use and cancer is encouraging - premature to recommend people to start taking aspirin specifically to prevent cancer
Case 4 CCS
Case 4 Treatment Options This patient accepted statin use He and wife asked; Doctor what other supplements may help? The health shop has suggested that fish-oil, Vitamin E, folic acid and resveretrol might be helpful. Is this questioning frequent in your practice and what is your attitude?
Vitamins Folic Acid High levels of homocysteine are associated with an increased risk of cardiovascular disease. Supplementation with folic acid, vitamin B6, and vitamin B12 can lower homocysteine levels. However, meta-analyses of randomized trials of supplementation for secondary prevention do not support the hypothesis that these vitamins are beneficial for cardiovascular disease
Vitamins Antioxidants Include total vitamin A, (preformed vitamin A (retinol) and the carotenoids such as betacarotene), vitamins C and E. Other compounds in food, especially vegetables and fruits, have antioxidant properties. A number of studies have examined the hypothesis that antioxidants can prevent cancer and cardiovascular disease by augmenting the body's ability to dispose of toxic free radicals, thereby retarding oxidative damage
Antioxidants Vitamin E Vitamin E compounds in sunflowers, wheat germ oil, corn, and nuts Current evidence does not support a role for vitamin E supplementation in the prevention or treatment of cancers, cardiovascular disease, dementia, and infection. High-dose vitamin E ( 400 units/day) might increase all-cause mortality Synergistic action of vitamin E with anticoagulants
Fish Oil Ecologic studies found low rates of coronary heart disease (CHD) death among Greenland Eskimos consuming large amounts of seafood Subsequent animal studies, observational studies, and clinical trials have examined the health effects of seafood consumption Influences several cardiovascular risk factors possibly via altered cell membrane fluidity and receptor responses
Fish Oil Initial studies - modest fish oil consumption may reduce the risk of CHD death and sudden cardiac death More recent RCTs failed to demonstrate significant effects, although a meta-analysis of placebocontrolled trials demonstrated modest reductions in CHD mortality Evidence for potentially-beneficial effects on CHD death and sudden cardiac death, and no evidence to suggest harm
Resveratrol Ingredient in red wine/grapes Antioxidant properties, reduced platelet aggregation - test-tube or tissue-culture preparations Most research has been on rodents 2011, a systematic review with 21 co-authors concluded that, "the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources done on animals
Case 4 CV Prevention Symptom assessment important Risk-assessment with traditional calculators and coronary calcium score Medical primary prevention is reliant on risk factor optimisation and statins
Herb-drug interactions St. John's wort induces the CYP3A4 system which metabolizes a number of drugs Ginkgo biloba has antiplatelet and antithrombotic effects and therefore has the potential to interact with anticoagulants Grapefruit juice and certain dihydropyridine calcium channel blockers