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1.
Am J Prev Cardiol ; 18: 100672, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38828126

RESUMO

Background: Primary prevention programs utilising traditional risk scores fail to identify all individuals who suffer acute cardiovascular events. We aimed to model the impact and cost effectiveness of incorporating a Polygenic risk scores (PRS) into the cardiovascular disease CVD primary prevention program in Australia, using a whole-of-system model. Methods: System dynamics models, encompassing acute and chronic CVD care in the Australian healthcare setting, assessing the cost-effectiveness of incorporating a CAD-PRS in the primary prevention setting. The time horizon was 10-years. Results: Pragmatically incorporating a CAD-PRS in the Australian primary prevention setting in middle-aged individuals already attending a Heart Health Check (HHC) who are determined to be at low or moderate risk based on the 5-year Framingham risk score (FRS), with conservative assumptions regarding uptake of PRS, could have prevented 2, 052 deaths over 10-years, and resulted in 24, 085 QALYs gained at a cost of $19, 945 per QALY with a net benefit of $724 million. If all Australians overs the age of 35 years old had their FRS and PRS performed, and acted upon, 12, 374 deaths and 60, 284 acute coronary events would be prevented, with 183, 682 QALYs gained at a cost of $18, 531 per QALY, with a net benefit of $5, 780 million. Conclusions: Incorporating a CAD-PRS in a contemporary primary prevention setting in Australia would result in substantial health and societal benefits and is cost-effective. The broader the uptake of CAD-PRS in the primary prevention setting in middle-aged Australians, the greater the impact and the more cost-effective the strategy.

2.
J Am Coll Cardiol ; 80(4): 373-387, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35863853

RESUMO

Risk factor-based models fail to accurately estimate risk in select populations, in particular younger individuals. A sizable number of people are also classified as being at intermediate risk, for whom the optimal preventive strategy could be more precise. Several personalized risk prediction tools, including coronary artery calcium scoring, polygenic risk scores, and metabolic risk scores may be able to improve risk assessment, pending supportive outcome data from clinical trials. Other tools may well emerge in the near future. A multidimensional approach to risk prediction holds the promise of precise risk prediction. This could allow for targeted prevention minimizing unnecessary costs and risks while maximizing benefits. High-risk individuals could also be identified early in life, creating opportunities to arrest the development of nascent coronary atherosclerosis and prevent future clinical events.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Cálcio/metabolismo , Doenças Cardiovasculares/prevenção & controle , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Humanos , Prevenção Primária/métodos , Medição de Risco/métodos , Fatores de Risco
3.
BMC Cardiovasc Disord ; 17(1): 228, 2017 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-28835227

RESUMO

BACKGROUND: Of the estimated 10-11 year life expectancy gap between Indigenous (Aboriginal and Torres Strait Islander people) and non-Indigenous Australians, approximately one quarter is attributable to cardiovascular disease (CVD). Risk prediction of CVD is imperfect, but particularly limited for Indigenous Australians. The BIRCH (Better Indigenous Risk stratification for Cardiac Health) project aims to identify and assess existing and novel markers of early disease and risk in Indigenous Australians to optimise health outcomes in this disadvantaged population. It further aims to determine whether these markers are relevant in non-Indigenous Australians. METHODS/DESIGN: BIRCH is a cross-sectional and prospective cohort study of Indigenous and non-Indigenous Australian adults (≥ 18 years) living in remote, regional and urban locations. Participants will be assessed for CVD risk factors, left ventricular mass and strain via echocardiography, sleep disordered breathing and quality via home-based polysomnography or actigraphy respectively, and plasma lipidomic profiles via mass spectrometry. Outcome data will comprise CVD events and death over a period of five years. DISCUSSION: Results of BIRCH may increase understanding regarding the factors underlying the increased burden of CVD in Indigenous Australians in this setting. Further, it may identify novel markers of early disease and risk to inform the development of more accurate prediction equations. Better identification of at-risk individuals will promote more effective primary and secondary preventive initiatives to reduce Indigenous Australian health disadvantage.


Assuntos
Doenças Cardiovasculares/etnologia , Disparidades nos Níveis de Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico , Actigrafia , Austrália/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/etnologia , Ecocardiografia , Humanos , Lipídeos/sangue , Espectrometria de Massas , Polissonografia , Prognóstico , Estudos Prospectivos , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/etnologia , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etnologia
4.
Lipids Health Dis ; 15: 67, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-27044508

RESUMO

BACKGROUND: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening. METHODS: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The LRS derived from SAFHS as well as its recalibrated version were validated in an independent cohort from Australia--the AusDiab cohort. The participants were T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n = 771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and clinically improved T2D prediction was evaluated with established statistical parameters in both cohorts. Modeling studies were conducted to determine whether the use of LRS would be cost-effective for T2D screening. The main outcome measures included accuracy and incremental value of the LRS over routinely used clinical predictors of T2D risk; validation of these results in an independent cohort and cost-effectiveness of including LRS in screening/intervention programs for T2D. RESULTS: The LRS was based on plasma concentration of dihydroceramide 18:0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The score predicted future T2D independently of prediabetes with an accuracy of 76%. Even in the subset of initially euglycemic individuals, the LRS improved T2D prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly and independently. When combined with risk-stratification methods currently used in clinical practice, the LRS significantly improved the model fit (p < 0.001), information content (p < 0.001), discrimination (p < 0.001) and reclassification (p < 0.001) in both cohorts. Modeling studies demonstrated that LRS-based risk-stratification combined with metformin supplementation for high-risk individuals was the most cost-effective strategy for T2D prevention. CONCLUSIONS: Considering the novelty, incremental value and cost-effectiveness of LRS it should be used for risk-stratification of future T2D.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/economia , Lipídeos/sangue , Biomarcadores/sangue , Estudos de Coortes , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/etiologia , Humanos , Resistência à Insulina , Reprodutibilidade dos Testes , Fatores de Risco
5.
PLoS One ; 10(6): e0130346, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26107182

RESUMO

Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.


Assuntos
Biomarcadores/sangue , Lipídeos/sangue , Cirrose Hepática Alcoólica/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Eur J Pediatr ; 162 Suppl 1: S34-7, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14610674

RESUMO

Lysosomal storage disorders have been recognised as one of the major groups of genetic disorders affecting children and adults. With over 40 different disorders and a combined prevalence of up to 1:5000 births, this group of disorders is a major public health problem and places an enormous burden on the individuals and families affected. Since the introduction of enzyme replacement therapy for Gaucher disease over 10 years ago there has been considerable progress in the development of enzyme based therapies for other disorders, in addition to alternate therapies including substrate deprivation and gene based therapies. Early diagnosis of these disorders before the onset of irreversible pathologies will lead to better outcomes for current and proposed therapies. In this review we describe the strategies and technology being used for the development of newborn screening for lysosomal storage disorders and discuss the future requirements for the early diagnosis and effective therapy of this group of disorders.


Assuntos
Doenças por Armazenamento dos Lisossomos , Triagem Neonatal/métodos , Tecnologia Biomédica/tendências , Transplante de Medula Óssea , Humanos , Recém-Nascido , Doenças por Armazenamento dos Lisossomos/diagnóstico , Doenças por Armazenamento dos Lisossomos/tratamento farmacológico , Doenças por Armazenamento dos Lisossomos/fisiopatologia , Triagem Neonatal/economia , Prevalência
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