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This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; P=0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; P<0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each P<0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: A

[This corrects the article DOI: 10.1016/j.ajpc.2021.100151.].

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10-3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.

People with diabetes are at risk of chronic complications and novel biomarkers, such as Advanced glycation end-products (AGEs) may help stratify this risk. We assessed whether plasma low-molecular weight AGEs, also known as LMW-fluorophores (LMW-F), are associated with risk factors, predict complications, and are altered by fenofibrate in adults with type 2 diabetes. Plasma LMW-F were quantified at baseline, after six weeks fenofibrate, and one year post-randomisation to fenofibrate or placebo. LMW-F associations with existing and new composite vascular complications were determined, and effects of fenofibrate assessed. LMW-F correlated positively with age, glycated haemoglobin (HbA1c), pulse pressure, kidney dysfunction and inflammation; and negatively with urate, body mass index, oxidative stress and leptin, albeit weakly (r = 0.04-0.16, all p < 0.01). Independent determinants of LMW-F included smoking, diastolic blood pressure, prior cardiovascular disease or microvascular complications, Caucasian ethnicity, kidney function, HbA1c and diabetes duration (all p ≤ 0.01). Baseline LMW-F tertiles correlated with on-trial macrovascular and microvascular complications (trend p < 0.001) on univariate analyses only. Six weeks of fenofibrate increased LMW-F levels by 21% (p < 0.001). In conclusion, LMW-F levels correlate with many risk factors and chronic diabetes complications, and are increased with fenofibrate. LMW-F tertiles predict complications, but not independently of traditional risk factors.

Introduction Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid‐lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time‐consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA. Materials and methods We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres. Results LDL‐cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time‐averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well‐tolerated, and patients reported comparable quality of life to population and disease‐related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors. Conclusion While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin‐like 3 inhibitors, may further reduce the need for LA.

Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease. New clinical practice recommendations are presented to assist practitioners in enhancing the care of all patients with FH. Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors and appropriate use of low-density lipoprotein (LDL)-cholesterol-lowering therapies including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The recommendations need to be utilised using judicious clinical judgement and shared decision-making with patients and families. New government-funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of the recommendations. However, a comprehensive implementation science and practice strategy is required to ensure that the guidance translates into benefit for all families with FH.

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits

INTRODUCTION: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH. MAIN RECOMMENDATIONS: Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. There is a key role for general practitioners (GPs) working in collaboration with specialists with expertise in lipidology. Advice is given on genetic and cholesterol testing and risk notification of biological relatives undergoing cascade testing for FH; all healthcare professionals should develop skills in genomic medicine. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors, and appropriate use of low-density lipoprotein (LDL)-cholesterol lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recommendations on service design are provided in the full guidance. POTENTIAL IMPACT ON CARE OF FH: These recommendations need to be utilised using judicious clinical judgement and shared decision making with patients and families. Models of care need to be adapted to both local and regional needs and resources. In Australia new government funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of these recommendations. A broad implementation science strategy is, however, required to ensure that the guidance translates into benefit for all families with FH.

[This corrects the article DOI: 10.1371/journal.pbio.3000870.].

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associ

OBJECTIVES: To assess the predictive value of the Australian absolute cardiovascular disease risk (ACVDR) calculator and other assessment tools for identifying Australians with family histories of early onset coronary artery disease (CAD) who have coronary artery calcification. DESIGN, SETTING, PARTICIPANTS: People without known CAD were recruited at seven Australian hospitals, October 2016 - January 2019. Participants were aged 40-70 years, had a family history of early onset CAD, and a 5-year ACVDR of 2-15%. MAIN OUTCOME MEASURES: CT coronary artery calcium score greater than zero (any coronary calcification) or greater than 100 (calcification warranting lipid therapy). RESULTS: 1059 participants were recruited; 477 (45%) had non-zero coronary artery calcium scores (median 5-year ACVDR, 4.8% [IQR, 2.9-7.6%]; median coronary artery calcium score, 41.7 [IQR, 8-124]); 582 (55%) did not (median 5-year ACVDR, 3.2% [IQR, 2.0-4.6%]). Of 151 participants with calcium scores of 100 or more, 116 (77%) were deemed to be at low cardiovascular risk by Australian guidelines, while 14 of 75 participants at intermediate risk (19%) had zero calcium scores. The sensitivity of the ACVDR calculator for identifying people with non-zero calcium scores (area under receiver operator curve [AUC], 0.674) was lower than that of the pooled cohort equation (AUC, 0.711; P < 0.001). ACVDR (10-year)- and Multi-Ethnic Study of Atherosclerosis (MESA)-predicted risk categories concurred for 511 participants (48%); classifications were concordant for 925 participants (87%) when the ACVDR was supplemented by calcium scores. CONCLUSIONS: Coronary artery calcium scoring should be considered as part of the heart health check for patients at intermediate ACVDR risk and with family histories of early onset CAD. Alternative risk calculators may better select such patients for further diagnostic testing and primary prevention therapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTR

BACKGROUND: This study examined the prevalence of risk factors for cardiovascular (CV)-related morbidity and mortality in young people with psychosis aged 18 to 24 years. METHODS: The study included 132 people aged 18 to 24 years who participated in the 2010 second Australian national survey of people living with psychosis. The 2009 World Health Organisation (WHO) Global Health Risks report was used as a framework to determine which specific risk factors were present in each in these young people. The risk factors assessed in this study were smoking, alcohol use, hypertension, overweight/obesity, physical inactivity, high blood glucose, high cholesterol and poor diet. Each risk factor was defined according to WHO criteria. A count of the total number of risk factors present for each participant was determined. Data for male and female participants were compared. RESULTS: Young men had an average of 2.9 (SD 1.2) risk factors. Young women had an average of 2.4 (SD 1.2) risk factors. The most common risk factors were low fruit and vegetable intake (77.9%), cigarette smoking (67.7%), overweight/obesity (55%) and physical inactivity (39.8%). There were no significant differences between men and women in the number of risk factors present, or the prevalence of individual risk factors. CONCLUSION: This study demonstrated that many of the risk factors that ultimately contribute to disability and premature death are present at an early age in people with psychosis. Preventive measures need to be an integral component of early intervention services for this client population to avert progression to serious CV morbidity and early mortality.

Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often under-treated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, web-based Rare Disease Registry Framework was the architecture chosen for this registry owing to its open-source standards, modular design, interoperability, scalability and security features; all these are key components required to meet the ever changing clinical demands across regions. This paper provides a high level blueprint for other countries and jurisdictions to help inform and map out the critical features of an FH registry to meet their particular health system needs.

BACKGROUND: Obstructive sleep apnea (OSA) in the general community is associated with obesity, smoking, alcohol, and sedative medication use and contributes to depressed mood, daytime sedation, and sudden cardiovascular deaths. Poor cardiovascular health, impaired social functioning, and negative and cognitive symptoms are also among the common clinical features of psychotic disorders. People with psychosis have higher rates of sleep disturbance; however, OSA has not been extensively investigated in this population. AIMS: This study aimed to determine the prevalence of OSA and general sleep disruption symptoms in a representative Australian sample of people with psychosis. We investigated the prevalence of potential risk factors for OSA, including obesity, psychotropic medications, and substance abuse in this population. Finally, we evaluated associations between symptoms of OSA, symptoms of general sleep disruption, and various clinical features in people with psychosis. METHODS: Participants took part in the Second National Australian Survey of Psychosis, a population-based survey of Australians with a psychotic disorder aged 18-64 years. Symptoms associated with OSA (snoring and breathing pauses during sleep) in the past year were assessed using questions from the University of Maryland Medical Centre Questionnaire and symptoms associated with general sleep disruption in the past week using the Assessment of Quality of Life Questionnaire. Data collected included psychiatric diagnosis and symptoms, education, employment, medications, smoking status, physical activity, drug and alcohol use, and cognitive function. Physical health measures included body mass index, waist circumference, blood pressure, fasting blood glucose, and lipids. RESULTS: Snoring was reported by 41.9%; 7% stating they frequently stopped breathing (pauses) during sleep. Univariate logistic regressions show OSA symptoms (pauses and snoring) were associated with older age, female gender, lower le

INTRODUCTION: In previous studies, we successfully designed complex multicompartmental microcapsules as a platform for the oral targeted delivery of lipophilic drugs in type 2 diabetes (T2D). Probucol (PB) is an antihyperlipidemic and antioxidant drug with the potential to show benefits in T2D. We aimed to create a novel microencapsulated formulation of PB and to examine the shape, size, and chemical, thermal, and rheological properties of these microcapsules in vitro. METHOD: Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using the polymer, sodium alginate (SA), empty (control, SA) and loaded (test, PB-SA) microcapsules were prepared at a constant ratio (1:30). Complete characterizations of microcapsules, in terms of morphology, thermal profiles, dispersity, and spectral studies, were carried out in triplicate. RESULTS: PB-SA microcapsules displayed uniform and homogeneous characteristics with an average diameter of 1 mm. The microcapsules exhibited pseudoplastic-thixotropic characteristics and showed no chemical interactions between the ingredients. These data were further supported by differential scanning calorimetric analysis and Fourier transform infrared spectral studies, suggesting microcapsule stability. CONCLUSION: The new PB-SA microcapsules have good structural properties and may be suitable for the oral delivery of PB in T2D. Further studies are required to examine the clinical efficacy and safety of PB in T2D.

Aims: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. Methods and results: Early diagnosis ofHoFHand prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH.We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensiveACVDevaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress tes

Individuals with psychosis are more likely than the general community to develop obesity and to die prematurely from heart disease. Interventions to improve cardiovascular outcomes are best targeted at the earliest indicators of risk, at the age they first emerge. We investigated which cardiometabolic risk indicators distinguished those with psychosis from the general population, by age by gender, and whether obesity explained the pattern of observed differences. Data was analyzed from an epidemiologically representative sample of 1,642 Australians with psychosis aged 18-64 years and a national comparator sample of 8,866 controls aged 25-64 years from the general population. Cubic b-splines were used to compare cross sectional age trends by gender for mean waist circumference, body mass index [BMI], blood pressure, fasting blood glucose, triglycerides, LDL, HDL, and total cholesterol in our psychosis and control samples. At age 25 individuals with psychosis had a significantly higher mean BMI, waist circumference, triglycerides, glucose [women only], and diastolic blood pressure and significantly lower HDL-cholesterol than controls. With the exception of triglycerides at age 60+ in men, and glucose in women at various ages, these differences were present at every age. Differences in BMI and waist circumference between samples, although dramatic, could not explain all differences in diastolic blood pressure, HDL-cholesterol or triglycerides but did explain differences in glucose. Psychosis has the hallmarks of insulin resistance by at least age 25. The entire syndrome, not just weight, should be a focus of intervention to reduce mortality from cardiovascular disease.

BACKGROUND: Patients with the metabolic syndrome are more likely to develop type 2 diabetes and may have an increased risk of cardiovascular disease (CVD) events.We aimed to establish whether CVD event rates were influenced by the metabolic syndrome as defined by the World Health Organisation (WHO), the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) and to determine which component(s) of the metabolic syndrome (MS) conferred the highest cardiovascular risk in in 4900 patients with type 2 diabetes allocated to placebo in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. RESEARCH DESIGN AND METHODS: We determined the influence of MS variables, as defined by NCEP ATPIII, IDF and WHO, on CVD risk over 5 years, after adjustment for CVD, sex, HbA1c, creatinine, and age, and interactions between the MS variables in a Cox proportional-hazards model. RESULTS: About 80% had hypertension, and about half had other features of the metabolic syndrome (IDF, ATPIII). There was no difference in the prevalence of metabolic syndrome variables between those with and without CVD at study entry. The WHO definition identified those at higher CVD risk across both sexes, all ages, and in those without prior CVD, while the ATPIII definition predicted risk only in those aged over 65 years and in men but not in women. Patients meeting the IDF definition did not have higher risk than those without IDF MS.CVD risk was strongly influenced by prior CVD, sex, age (particularly in women), baseline HbA1c, renal dysfunction, hypertension, and dyslipidemia (low HDL-c, triglycerides > 1.7 mmol/L). The combination of low HDL-c and marked hypertriglyceridemia (> 2.3 mmol/L) increased CVD risk by 41%. Baseline systolic blood pressure increased risk by 16% per 10 mmHg in those with no prior CVD, but had no effect in those with CVD. In those without prior CVD, increasing numbers of metabolic syndrome v

OBJECTIVE: Subjects with the metabolic syndrome have reduced HDL cholesterol concentration and altered metabolism of high-density lipoprotein (Lp)A-I and LpA-I:A-II particles. In the metabolic syndrome, fenofibrate and atorvastatin may have differential effects on HDL particle kinetics. RESEARCH DESIGN AND METHODS: Eleven men with metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-week intervention periods with placebo, fenofibrate (200 mg/day), and atorvastatin (40 mg/day). LpA-I and LpA-I:A-II kinetics were examined using stable isotopic techniques and compartmental modeling. RESULTS: Compared with placebo, fenofibrate significantly increased the production of both LpA-I:A-II (30% increase; P < 0.001) and apoA-II (43% increase; P < 0.001), accounting for significant increases of their corresponding plasma concentrations (10 and 23% increases, respectively), but it did not alter LpA-I kinetics or concentration. Atorvastatin did not significantly alter HDL concentration or the kinetics of HDL particles. CONCLUSIONS: In the metabolic syndrome, fenofibrate, but not atorvastatin, influences HDL metabolism by increasing the transport of LpA-I:A-II particles.