Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase and may influence the secretion and uptake of various lipoproteins.Genetic studies show that depletion of these proteins is associated with improved lipid profiles and reduced cardiovascular events so it was anticipated that drugs which mimic the effects of loss-of-function mutations would be useful lipid treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), which is usually not adequately controlled with currently available drugs. However, it was found ANGPTL3 inhibitors were also effective in reducing low-density lipoprotein cholesterol (LDL-C) and they were studied in patients with homozygous familial hypercholesterolaemia (FH). Evinacumab targets ANGPTL3 and reduced LDL-C by about 50% in patients with homozygous FH and it has been approved for that indication. The antisense oligonucleotide (ASO) vupanorsen targeting ANGPTL3 was less effective in reducing LDL-C in patients with moderate hypertriglyceridaemia and its development has been discontinued but the small interfering RNA (siRNA) ARO-ANG3 is being investigated in Phase 2 studies. ApoC3 can be inhibited by the ASO volanesorsen, which reduced triglycerides by >70% in patients with FCS and it was approved for FCS in Europe but not in the United States because of concerns about thrombocytopaenia. Olezarsen is an N-acetylgalactosamine-conjugated ASO targeting apoC3 which appears as effective as volanesorsen without the risk of thrombocytopaenia and is undergoing Phase 3 trials. AROAPOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies.

BACKGROUNDRosuvastatin has been claimed to be more potent than other statins in its ability to lower the low-density lipoprotein (LDL) cholesterol levels. This study aimed to investigate the clinical efficacy of rosuvastatin in LDL cholesterol lowering therapy for new or switched hyperlipidaemic Chinese patients.

METHODSThis study was a retrospective one in patients who took rosuvastatin in the outpatient clinics of Prince of Wales Hospital during the period of July 1, 2004 to June 30, 2005. The prescribing pattern, the utilization pattern and the side effect profile were recorded. Attainment of lipid goals for each patient was assessed according to the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III guidelines.

RESULTSA total of 261 Chinese patients (mean age (64.8 +/- 12) years; 55.6% male) were recruited into the study. The mean LDL-cholesterol level was (3.50 +/- 1.29) mmol/L prior to Rosuvastatin and (2.30 +/- 1.73) mmol/L after Rosuvastatin treatment (P < 0.0001). Rosuvastatin raised the LDL-cholesterol goal achievement rate from 28.0% to 74.3% in all patients combined (P < 0.0001) and from 11.0% to 79.0% for statin naive patients (P < 0.0001). Approximately 4% of patients developed side effects including myalgia, elevated liver enzymes, and dizziness.

CONCLUSIONRosuvastatin was effective in improving LDL-cholesterol goal attainment and lowering LDL-cholesterol and triglyceride (TG) levels in either newly started or switched patients.

Adult ; Aged ; Cholesterol, LDL ; blood ; Female ; Fluorobenzenes ; adverse effects ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Male ; Middle Aged ; Pyrimidines ; adverse effects ; therapeutic use ; Retrospective Studies ; Rosuvastatin Calcium ; Sulfonamides ; adverse effects ; therapeutic use

OBJECTIVETo investigate the relative effects of degree and distribution of body fat with several cardiovascular disease (CVD) risk factors in elderly Chinese subjects.

METHODSOne hundred and thirty-five elderly Chinese individuals (age range, 60-65 y) without any history of significant renal, hepatic or cardiac disease were recruited. Seated blood pressure, anthropometric and fasting plasma biochemical parameters were measured. Student's t-test was used to compare the differences in biochemical and anthropometric markers between cohorts.

RESULTSMales were heavier (64.6 +/- 8.6, 57.2 +/- 8.2kg, P < 0.001), taller (1.65 +/- 0.06, 1.51 +/- 0.05 m, P < 0.001) and their greater body fat was predominantly deposited centrally (Waist-to- hip ratio, 0.91 +/- 0.06, 0.88 +/- 0.07, P < 0.05). Females were more generally obese with increased body mass index (BMI, 23.8 +/- 4.6, 25.0 +/- 3.5 kg/m2, P < 0.05) and percentage body fat [26.3% (24.5%-28.1%) vs 37.2% (36.0%-38.9%), P < 0.001] than the males. However, despite an 11% higher proportion of body fat in females, no significant differences were identified in blood pressure, lipid profile, indices of insulin resistance or albumin-to-creatinine ratios.

CONCLUSIONIt is likely that central adiposity contributes disproportionately to these metabolic disorders in males even though they are much leaner than elderly Chinese females.

Adult ; Aged ; Body Mass Index ; Cardiovascular Diseases ; etiology ; Female ; Humans ; Male ; Middle Aged ; Obesity ; complications ; Risk Factors

PURPOSETo review evidence-based management of nephropathy in patients with type 2 diabetes.

DATA SOURCESA literature search (MEDLINE 1966 to 2000) was performed using the key word "diabetic nephropathy". Relevant book chapters were also reviewed.

STUDY SELECTIONWell-controlled, prospective landmark studies and expert review articles on diabetic nephropathy were selected.

DATA EXTRACTIONData and conclusions from the selected articles that provide solid evidence to the optimal management of diabetic nephropathy were extracted and interpreted in light of our clinical research experience with many thousands of Hong Kong Chinese patients.

RESULTSHypertension, long diabetes duration, poor glycaemic control and central obesity are the most important risk factors. Microalbuminuria is a practical marker to predict overt nephropathy in type 2 diabetic patients. Risk factor modification, renal function monitoring and combined therapies are the current integrated approaches to manage patients with diabetic kidney disease. Optimal glycaemic control is the mainstay of treatment but effective antihypertensive therapy is also key to delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have important renoprotective actions independent of their blood pressure lowering actions.

CONCLUSIONSDiabetic nephropathy is the leading cause of end-stage renal disease worldwide. Monitoring renal function and screening for microalbuminuria will allow the identification of patients with nephropathy at a very early stage for intervention. Tight glycaemic control and aggressive antihypertensive treatment as well as the use of renin-angiotensin system inhibitors should substantially delay the progression of nephropathy.

Albuminuria ; diagnosis ; therapy ; Blood Glucose ; analysis ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Nephropathies ; epidemiology ; therapy ; Dietary Proteins ; administration & dosage ; Humans ; Hyperlipidemias ; therapy ; Hypertension ; therapy