Angioplasty:
Percutaneous transluminal coronary angioplasty (PTCA) is a widely used and effective method to restor coronary flow in patients with symptomatic cornary artery disease.
Statins:
Stations are a class of medications that have been shown to be effective in lowering human total cholesterol, LDLC and triglyceride levels. Statins act at the step of cholesterol synthesis. By reducing the amount of cholesterol synthesized by the cell, thorugh inhibition of the HMG-CoA reductase gene, statins initiate a cycle of events that culminates in the increase of LDLC uptake by liver cells. As LDLC uptake is increased, total cholesterol and LDLC levels in the blood decrease. Lower blood levels of both factors are associated with lower risk of atheroscleorsis and heart-disease, and the statins are widely used to reduce atherosclerotic mobidity and mortality. Examples of statins include simvastatin (Zocor0, lovastatin (Mevacor), pravastatin (Pravachol), fluvastatin (Lescol), atorvastatin (Lipitor), cerivastatin (Baycol), rosuvastatin (Crestor), and pitivastatin. (Ridker, US Patent Application No: 14/886626, published as US 2016/026146).
Statin therapy lowers the risk of cardiovascular evetns by reducign plasma cholesterol and practice guidelines for patients with known cardiovascular disease emphasize the important of reaching target goals of LDLC. (US 14/886626, published as US 2016/026146).
Statin therapy has been shown to reduce the level of C reactive protein independently of its effects on lipid levels. Ridker, N England J Medicine 344 No. 26, 2001. See as Ridker (European Heart J. (2001) 22, 2135-2137). In a double blind trial of mean and women with no prior history of CVD (primary prevention cohort) and open label study of people with known CVD (secondary prevention cohort), pravastatin reduced CRP levels at both 12 and 24 weeks in a largely LDL C independent manner (Albert, JAMA, 286(1), 2001).
However, Ridker (“Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial” (lancet.com, vol 373, April 2009) showed that although LDL cholesterol and hsCRP reductions were only weakly correlelated in individual patients, there was a 65% reduction in vascular events in participants allocated to rosuvastatin who achieved both LDL cholesterol less than 1.8 mmol/L and hsCRP less than 2 mg/L versus a 33% reduction in those who acheived one or neither target.
Effect of Statins on CRP Levels
Hypolipidaemic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reducatase inhibitor (statin) treatment reduces cardiovascular risk and is also assocatied with the reduction of C-reactive protein (CRP) concentration. (Strandberg, Ann Med, 32(8), pp. 579-83 (2000) Statins are often prescribed to reduce the risk of a future cardivascular event in human subjects with abnormally high cholesterol and-or LDLC levels. It is known that lipid lowering statin therapy lowers not only cholesterol but also lowers the level of CRP. Ridker US2007-0292960
Effects of Statin Treatment on Lipid levels (e.g., LDL, HDL, triglycerides)
Hypolipidaemic 3-hyroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment reduces cardiovascular risk and is also associated with the reduction of CRP concentrations. In addition, low-desnity lipoprotein (LDL) cholesterol was substantially decreased and HDL cholesterol increased during statin treatment. The changes of CRP were significantly associated with changes in HDL and apolipoprotein A1 but not with changes in LDL cholesterol or triglycerides. (Strandberg, “Associations between change in C-teactive protein and serum lipids during statin treatment” Ann Med 2000, 32: 579-583)
Satins + Ezetimibe:
The addition of ezetimibe to statin treatment provides significantly enhanced CRP reductions over and above those achieved with statin monotherpay. (Pearson, Am J. Cardiol. 2009, 103(3), 369-74).
PPAR-alpha
Fibrates (activators of peroxisome proliferators-activated receptor-alpha (PPAR-alpha): have been available for the treamtnet of dyslipidemia (lipid disorders) since the 1970s and are currently widely used behind statins. Fibrates have been well documented to reduce the risk of coronary events through the beneficial effects on lipoproteins such as lowering serum triglyceride and raising HDL. Fibrates can also reduce CRP concentrations and this change in CRP is correlated with change in HDL but not with triglyceride. (Hao, Clin Chem Lab Med 2012, 50(2) 391-397, 2012).
PSC9 Inhibitors
RNA inhbitors:
Inclisiran (The Medicines Company which has been aquired by Merck): is a small interfering RNA that inhibitors PSC9. It has shown positive results in a phase III clinical study. It treats familial hypercholesteroleaoma.
PS