👤 Hiroyuki Daida

Limited evidence exists on the role of lipoprotein(a) [Lp(a)] in the progression of atherosclerotic coronary plaques as assessed by intravascular imaging modality, particularly under low-density lipoprotein cholesterol (LDL-C) lowering therapy. In this study, we aimed to evaluate the clinical significance of Lp(a) as a residual risk factor for coronary plaque progression, using serial intravascular ultrasound (IVUS) in statin-treated patients with coronary artery disease (CAD). This observational cohort study included statin-treated patients from two clinical prospective trials (the ENTERPRISE trial and Extended-ESTABLISH trial) in which coronary plaques were assessed using serial grayscale IVUS at baseline and at 6-12 months follow-up. The primary endpoints were defined as absolute changes in normalized total atheroma volume (TAV Show less

Primary chylomicronemia (PCM) is a rare and intractable disease characterized by marked accumulation of chylomicrons in plasma. The levels of plasma triglycerides (TGs) typically range from 1,000 - 15,000 mg/dL or higher.PCM is caused by defects in the lipoprotein lipase (LPL) pathway due to genetic mutations, autoantibodies, or unidentified causes. The monogenic type is typically inherited as an autosomal recessive trait with loss-of-function mutations in LPL pathway genes (LPL, LMF1, GPIHBP1, APOC2, and APOA5). Secondary/environmental factors (diabetes, alcohol intake, pregnancy, etc.) often exacerbate hypertriglyceridemia (HTG). The signs, symptoms, and complications of chylomicronemia include eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, and acute pancreatitis with onset as early as in infancy. Acute pancreatitis can be fatal and recurrent episodes of abdominal pain may lead to dietary fat intolerance and failure to thrive.The main goal of treatment is to prevent acute pancreatitis by reducing plasma TG levels to at least less than 500-1,000 mg/dL. However, current TG-lowering medications are generally ineffective for PCM. The only other treatment options are modulation of secondary/environmental factors. Most patients need strict dietary fat restriction, which is often difficult to maintain and likely affects their quality of life.Timely diagnosis is critical for the best prognosis with currently available management, but PCM is often misdiagnosed and undertreated. The aim of this review is firstly to summarize the pathogenesis, signs, symptoms, diagnosis, and management of PCM, and secondly to propose simple diagnostic criteria that can be readily translated into general clinical practice to improve the diagnostic rate of PCM. In fact, these criteria are currently used to define eligibility to receive social support from the Japanese government for PCM as a rare and intractable disease.Nevertheless, further research to unravel the molecular pathogenesis and develop effective therapeutic modalities is warranted. Nationwide registry research on PCM is currently ongoing in Japan with the aim of better understanding the disease burden as well as the unmet needs of this life-threatening disease with poor therapeutic options. Show less

We aimed to assess the effects of cholesteryl ester transfer protein inhibitor anacetrapib added to statin ± other lipid-modifying therapies (LMT) in Japanese patients with dyslipidemia who were not at their LDL-C goal. Patients on a stable dose of statin ± other LMT with LDL-C ≥100 mg/dL to <145 mg/dL, ≥120 mg/dL to <165 mg/dL, ≥140 mg/dL or ≥160 mg/dL for patients with a history of coronary heart disease (CHD), high-, moderate- and low-risk patients respectively, were randomized 2:1, stratified by background therapy, to double-blind anacetrapib 100 mg (n = 204) or placebo (n = 103) for 24 weeks, followed by a 28-week open-label extension phase (anacetrapib 100 mg) and a 12-week off-drug safety follow-up phase. The primary endpoint was percent change from baseline in LDL-C (beta-quantification method), as well as the safety profile of anacetrapib at Week 24; HDL-C was a key secondary endpoint. Anacetrapib 100 mg further reduced LDL-C (38.0%), non-HDL-C (35.1%), ApoB (28.7%), and Lp(a) (48.3%) and increased HDL-C (148.9%) and ApoAI (50.7%) versus placebo (p < 0.001 for all). There were no meaningful differences between the groups in the proportion of patients with liver enzymes elevations (2.0% vs. 0%), creatine kinase elevations overall (0.5% vs. 0%) or with muscle symptoms (0.5% vs. 0%), blood pressure, electrolytes or adjudicated cardiovascular events (0.5% vs. 0%). In the open-label period, sustained effects on lipid parameters were observed with anacetrapib and the treatment was generally well tolerated. Long-term treatment with anacetrapib 100 mg substantially reduced LDL-C, increased HDL-C and was well tolerated in Japanese patients with dyslipidemia (ClinicalTrials.gov number NCT01760460). Show less