Trajectories of lipids profile and incident cvd risk

Changing from conventional lipid fractions to novel fractions

1. Trajectories of Lipids Profile and Incident Cardiovascular Disease Risk Dr. Nagula Praveen MD,DM ( Cardiology)

2. Risk factors for ACS

3. Changing phenotype of the ACS patient The phenotype of the typical patient with acute coronary syndrome of yesteryear Thin Anxious Chain-smoking executive with high levels of LDL cholesterol The phenotype of the contemporary patient Overweight Sedentary patient with a greater risk due to diabetes, metabolic syndrome, and High triglyceride/low HDL cholesterol levels. Vasc Health Risk Manag . 2013; 9: 617–670. Atherosclerosis leads to CVD

4. Prevalence of risk factors by country income groups Risk factors, % of population Low income Low middle income Upper middle income High income Tobacco use, men 31 32 43 33 Tobacco use, women 3 3 5 18 Insufficient physical activity 17 17 25 33 Overweight 21 27 43 56 High blood pressure 28 25 20 19 High cholesterol 24 32 46 59 High fasting glucose 7 9 9 7 Anand , S., et al. BMC Med 18, 7 (2020):https://doi.org/10.1186/s12916-019-1480-9.

5. Risk factors for CAD in Indians >40 years and < 40 years of age Journal of Practice of Cardiovascular Sciences: 2019 : 2019: 5(1): 18-25.

6. Pattern of coronary artery lesion observed in a tertiary care hospital in India Indian Heart Journal: 2014:66:156-163.

7. Unravelling the role of lipid fractions in CAD

8. LIPIDS have been unanimously implicated in atherosclerosis …. BUT…

9. Conventional LIPID risk factors for CVD High LDL Low HDLc High triglycerides

10. NHANES The latest National Health and Nutrition Examination Survey (NHANES) data suggest that 53% of US adults have lipid abnormalities, Of whom 27% have high LDL cholesterol 23% have low HDL cholesterol, and 30% have high triglyceride levels Vasc Health Risk Manag . 2013; 9: 617–670. The lowest levels of HDL cholesterol, there was a 12-fold increase in mortality risk for those with coronary heart disease

11. LDL fall has to accompanied by changes in HDL and TG When LDL cholesterol is controlled , the odds of coronary heart disease .. Fall by 40% per 7.5 mg/ dL rise in HDL cholesterol Increase by 20% per 23 mg/ dL rise in triglyceride levels Vasc Health Risk Manag . 2013; 9: 617–670.

12. Statins are the most frequently prescribed agents for primary and secondary prevention of coronary heart disease, the leading cause of death globally.  Vasc Health Risk Manag . 2013; 9: 617–670. LDL lowering is addressed aggressively by statins today based on risk stratification

13. The hs -CRP level achieved after initiation of statin therapy may be as important as the LDL cholesterol level achieved.  The American Journal of Cardiology : 2006: 97(2):33-41 .

14. Linear relationship between low-density lipoprotein-cholesterol (LDL-C) reduction and cardiovascular events reduction Circulation Cardiovascular Quality and Outcomes: 2014:7(2)

15. Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease Event Rates Plotted against LDL Cholesterol Levels during Statin Therapy in Secondary-Prevention Studies. 22 % relative reduction in the risk of the primary composite end point with 80 mg of atorvastatin If these results were extrapolated to clinical practice , .. 80-mg dose of atorvastatin used to reduce LDL cholesterol levels from a baseline of 101 mg per deciliter to 77 mg per deciliter in 1000 patients with stable CHD would ….. prevent 34 major cardiovascular events over a period of five years. N Engl J Med 2005; 352:1425-1435.

16. Rosuvastatin treatment causes a 44% reduction in primary end point

17. Low HDL and CV risk Journal of Clinical Lipidology : 2016. A large proportion of very high and high ASCVD patients are not at recommended non–HDL-C targets and hence remain at a substantial residual risk

18. Role of triglycerides

19. Triglycerides and CV risk in women In women, changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels are better predictors of coronary risk than LDL-C or total cholesterol. Treatment beyond LDL-C may be of greater importance in women than in men. Treatment options that provide improvement in all aspects of the lipid profile should be considered. J Am Board Fam Pract 2004;17:424 –37.

20. LDL in diabetes patients Glycated small dense LDL predominates heavily among glycated ApoB -containing lipoproteins. The amount of glycated ApoB in the plasma correlates not with HbA 1c , but with the amount of small dense LDL. Statins effectively lower small dense LDL cholesterol levels, leading to a lower glycated LDL burden in diabetics. Vasc Health Risk Manag . 2013; 9: 617–670.

21. DALI study : Aggressive treatment with atorvastatin in diabetic dyslipidemia Higher reduction in LDL, TC with atorvastatin 80 mg Diabetes Care : 2001: 24(8): 1335-1341.

22. Residual risk still persisting with statins in major statin trials Indian Journal of Endocrinology and Metabolism : 2016: 20(4):418-428.

23. HDL: Quantity or Quality : What matters ? Impaired sterol efflux capacity might be a marker and perhaps mediator of atherosclerotic burden Quantification of chlorotyrosine and oxidized methionine in circulating HDL might be useful indicators of the risk of cardiovascular disease that are independent of HDL cholesterol. Journal of Lipids Volume 2015, Article ID 971453, 50 pages http://dx.doi.org/10.1155/2015/971453.

24. Summary of pleiotropic effects of HDL HDL quality may be more important than HDL quantity Cholesterol 2013(10):891403.

25. Controversies surrounding the “HDL hypothesis.” Cholesterol, vol. 2013, Article ID 891403, 18 pages, 2013. https://doi.org/10.1155/2013/891403

26. Dysfunctional HDL in CHD HDL from the plasma of patients with stable coronary heart disease or acute coronary syndrome Carry a protein cargo distinct from that of healthy subjects. Can become proinflammatory regardless of the plasma LDL cholesterol concentration.  Such “dysfunctional” HDL cannot Stimulate endothelial repair Inhibit secretion of vascular cell adhesion molecule 1 Suppress activation of NF- κ B , or reduce expression of LDL-induced endothelial monocyte chemoattractant protein and consequent monocyte adhesion, and May stimulate endothelial proapoptotic signaling pathways. Vasc Health Risk Manag . 2013; 9: 617–670.

27. Other CV risk biomarkers to look for?

28. Non-high-density Lipoprotein Cholesterol Non-HDL-C represents the cholesterol contained in all lipoproteins except HDL-C Non HDLc = TC- HDL-C. It serves as a better surrogate for the overall atherogenic burden than LDL-C alone, making it a useful marker in the assessment of CVD risk. Currently, several important guidelines have flagged non-HDL-C as a primary therapeutic target for patients with CHD International Atherosclerosis Society (IAS) guideline National Lipid Association (NLA) guideline and National Institute for Health and Care Excellence (NICE) guideline European Cardiology Review 2020;15:e56. Lipids Health Dis: 2019: 18: 134.

29. ApoB and apoA -I ApoB and apoA -I are the two major apolipoproteins involved in lipid transport and in the processes causing atherosclerosis and its complications. ApoB is the major protein in Very Low Density (VLDL), Intermediate Density (IDL) and Low Density Lipoproteins (LDL), one protein per particle (1). ApoA -I is the major protein in High Density Lipoprotein (HDL) particle Lancet 2001;358:2026-2033.

30. ApoB containing lipoproteins

31. Clinical utility for CV risk prediction : Which biomarker is better?

32. The AMORIS study Apo A was a stronger predictor of risk then LDLc Chapter from the book Lipoproteins - Role in Health and Diseases Downloaded from: http://www.intechopen.com/books/lipoproteins-role-in-health-anddiseases Lancet 2001;358:2026-2033. Recruited 175553 individuals mainly from screening programmes Mean follow-up was 66.8 months men ) and 64.4 months(women) Measured concentrations of apoB , apoA -I, total cholesterol, and triglycerides, Calculated apoB / apoA -I ratio and concentrations of LDL-cholesterol and HDL-cholesterol. 

33. The apoB / apoA -I Ratio is a Strong Predictor of Cardiovascular Risk Tentative cut-values are indicated in green (low risk), yellow (medium risk), and red (high risk). Values for a particular patient can be indicated by the dots on the line. During lipid-lowering treatment it is easy to monitor how a patient moves upwards or downwards in the risk line for the apo -ratio. apoB , apoA -I, and especially the apo -ratio, are at least equally good, or often even better than conventional lipids to predict CV risk prospectively and during lipid-lowering treatment . Chapter from the book Lipoproteins - Role in Health and Diseases Downloaded from: http://www.intechopen.com/books/lipoproteins-role-in-health-anddiseases

34. Lp (a)

35. Lp (a) and CV risk Lp (a) Was found to infiltrate into the vascular intima and atherosclerotic lesions, and Accumulates at sites of vascular injury, probably related to its ability to bind fibrin High Lp (a) plasma levels could be considered a residual cardiovascular risk factor in patients on statin therapy Lp (a) levels may be useful to predict the onset of coronary heart disease rather than its progression to cardiovascular death Chapter from the book Lipoproteins - Role in Health and Diseases Downloaded from: http://www.intechopen.com/books/lipoproteins-role-in-health-anddiseases

36. Lp (a): What do the guidelines say? The 2019 ESC/EAS guideline Suggests measurement of Lp (a) at least once in each individual’s lifetime to identify people with high levels, signifying a very high lifetime risk of CVD. The 2018 AHA/ACC cholesterol guideline Considers a Lp (a) ≥125 nmol /l (≥50 mg/dl) as a risk-enhancing factor Its measurement can be considered in patients with a strong family history of premature CVD, people with familial hypercholesterolaemia , or personal history of CVD not explained by other traditional risk factors European Cardiology Review 2020;15 :e56.

37. End note Advanced lipid testing encompasses a wide range of diagnostic laboratory tests We need to look beyond the conventional high LDL, low HDL and high TG Selective use of lipid and lipoprotein biomarkers enhance prediction of CVD risk in patients whose risk is difficult to discern and helps the assessment of the efficacy of lipid-lowering therapy. Further studies are warranted to better understand the usefulness of these risk biomarkers. European Cardiology Review 2020;15:e56.

38. End note Additionally, variability of assay methodology and reporting also serve as a barrier for widespread clinical implementation. As of now, the most promising markers are non-HDL-C, apoB , and Lp (a) When used in the appropriate context, they can provide incremental prognostic information, enhance shared decision-making and inform therapeutic decisions to improve cardiovascular health. European Cardiology Review 2020;15:e56.

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