A lipid-lowering drug that significantly increases lipoprotein-a levels?

Ans. C (Rosuvastatin) (Ref. Evidence that elevated lipoprotein(a) (Lp) levels contribute to cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS) is substantial. Development of isoform-independent assays, in concert with genetic, epidemiological, translational, and pathophysiological insights, have established Lp(a) as an independent, genetic, and likely causal risk factor for CVD and CAVS. These observations are consistent across a broad spectrum of patients, risk factors, and concomitant therapies, including patients with low-density lipoprotein cholesterol <70 mg/dl. Statins tend to increase Lp(a) levels, possibly contributing to the "residual risk" noted in outcomes trials and at the bedside. Recently approved proprotein convertase subtilisin/kexin-type 9 inhibitors and mipomersen lower Lp(a) 20% to 30%, and emerging RNA-targeted therapies lower Lp(a) >80%. These approaches will allow testing of the "Lp(a) hypothesis" in clinical trials. This review summarizes the current landscape of Lp(a), discusses controversies, and reviews emerging therapies to reduce plasma Lp(a) levels to decrease risk of CVD and CAVS. Niacin (but not niacinamide) decreases VLDL and LDL levels--and Lp(a). It often increases HDL levels significantly. It is particularly useful in patients with combined hyperlipidemia and low plasma levels of HDL-C and is effective in combination with statins. NIACIN (NICOTINIC ACID) Mechanism of Action # Niacin inhibits VLDL secretion, in turn decreasing production of LDL. # Increased clearance of VLDL via the LPL pathway contributes to triglyceride reduction. # The catabolic rate for HDL is decreased. # Fibrinogen levels are reduced, and levels of tissue plasminogen activator appear to increase. # Niacin inhibits the intracellular lipase of adipose tissue via receptor-mediated signaling, possibly reducing VLDL production by decreasing the flux of free fatty acids to liver. # Nicotinic acid decreases both LDL-C and VLDL-C, while raising plasma HDL1-C, and is frequently effective for Familial hypercholestremia when used in combination with HMG-CoA reductase inhibitors. # Niacin is the only currently available lipid-lowering drug that significantly reduces plasma levels of Lp(a).deg # It is the most effective drug currently available for raising HDL-C levels. # NOTE: Lipoprotein-a is marker of HDL while Lipoprotein-B 100 is marker of LDL. Therapeutic Uses & Dosage # In combination with a resin or reductase inhibitor, niacin normalizes LDL in most patients with heterozygous familial hypercholesterolemia and other forms of hypercholesterolemia. These combinations are also indicated in nephrosis. # It is clearly the most effective agent for increasing levels of HDL. Toxicity # Cutaneous vasodilation and sensation ot warmth after each dose. # Pruritus, rashes, dry skin or mucous membranes, and acanthosis nigricans. # Rarely, true hepatotoxicity. # Rarely, arrhythmias, mostly atrial # Reversible toxic amblyopia. # Tachyphylaxis. # Peptic disease. # Dysglycemia # Hyperuricemia. Drug Major Indications Common Side Effects HMG-CoA reductase inhibitors (statins) Elevated LDL-C Myalgias, arthralgias, elevated transaminases,dyspepsia Cholesterol absorption inhibitors (Ezetimibe) Elevated LDL-C Elevated transaminases Nicotinic acid Elevated LDL-C and TG, low HDL-C, Skin flushing, Gl upset, elevated glucose, uric acid, LFTs. Fibric acid derivatives (Gemfibrozil, Fenofibrate) Elevated TG, elevated remnants Dyspepsia, myalgia, gallstones, elevated transaminases Omega-3 fatty acids Elevated TG Dyspepsia, diarrhea, fishy odor to breath Bile acid sequestrants (Cholestyramine, Colestipol, Colesevelam) Elevated LDL-C Bloating, constipation, elevated triglycerides