Abstract
Objectives: Our aim was to investigate the effects of reconstituted high-density lipoprotein (rHDL) infusions on plasma high-density lipoprotein (HDL) anti-inflammatory properties and ex vivo cholesterol efflux in patients with type 2 diabetes.
Background: The anti-inflammatory effects of HDL contribute to protection from cardiovascular events. Individuals with type 2 diabetes are at elevated risk for cardiovascular disease, and typically have low HDL with reduced anti-inflammatory properties.
Methods: Thirteen fasting male patients (mean age 52 years) with type 2 diabetes mellitus received both rHDL (80 mg/kg of apolipoprotein A-I) and a saline placebo on separate occasions in a randomized cross-over design study. Changes in the ability of isolated HDL to influence the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human coronary artery endothelial cells was the main outcome measure. Other outcome measures included expression of the key integrin, CD11b on patient monocytes, adhesiveness of patient neutrophils to fibrinogen, and the ability of plasma to promote cholesterol efflux to THP-1 macrophages.
Results: Four and 72 h post-rHDL infusion, the anti-inflammatory properties of isolated HDL increased in parallel to their concentration in plasma (by up to 25%, p < 0.01). Participants' peripheral blood monocyte CD11b expression and neutrophil adhesion to a fibrinogen matrix was also reduced 72 h post-rHDL, compared with that seen in placebo (p = 0.02). rHDL increased the capacity of plasma to receive cholesterol from THP-1 macrophages by 1 h up to 72 h post-infusion (by 40% to 60%, p < 0.05).
Conclusions: rHDL infusions have significant, potentially atheroprotective effects in individuals with diabetes, including suppression of inflammation and enhancement of cholesterol efflux.
Journal of the American College of Cardiology, Volume 53, Issue 11, Pages 962-971
S. Patel, B. Drew, S. Nakhla, S. Duffy, A. Murphy, P. Barter, K. Rye, J. Chin-Dusting, A. Hoang, D. Sviridov
Showing posts with label cardiovascular disease. Show all posts
Showing posts with label cardiovascular disease. Show all posts
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Lipid treatment guidelines and cardiovascular risk for Aboriginal people in Central Australia
OBJECTIVE: To evaluate the extent to which the current Pharmaceutical Benefits Scheme (PBS) guidelines for patient eligibility for lipid-lowering medication are applicable to Aboriginal people in Central Australia.
DESIGN, SETTING AND PARTICIPANTS: A 10-year cohort study of 659 Aboriginal people who participated in population-based cardiovascular disease (CVD) risk factor surveys in 1995 and who were free of CVD at baseline, for the period from 1995 to 2004-2005 or until first CVD event. Evidence of atherosclerotic CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) was sought from hospital, primary health care and death records. PBS eligibility was assigned according to the current PBS criteria, which were amended in 2006 to include Aboriginal-specific criteria, using participants' baseline (1995) and 10-year follow-up data.
MAIN OUTCOME MEASURES: Proportions of PBS-eligible and PBS-ineligible participants who had CVD events during the study period; sensitivity and specificity of the criteria. RESULTS: Of 42 participants who had CVD events during the study period, 35 were PBS-eligible (incidence, 1130/100 000 person-years; relative risk compared with PBS-ineligible population, 4.87 [95% CI, 2.19-10.80]) and seven were PBS-ineligible. PBS eligibility was associated with older mean age (37 v 32 years) and male sex (48% v 37%), with 50.7% of participants (334/659) meeting eligibility criteria. The mean high-density lipoprotein cholesterol level at baseline was very low in both groups (0.81 v 0.87 mmol/L). The current PBS guidelines have low specificity (52%) in this population, which was found to improve (to 71%-82%) by incorporating additional non-lipid criteria (age and multiple non-lipid risk factors).
CONCLUSION: The current PBS lipid treatment criteria, which include any Aboriginal person with diabetes and less stringent cholesterol thresholds than the previous version, identify a group at very high risk of CVD. Global risk assessment may better identify those at risk.
Onemda VicHealth Koori Health Unit, Centre for Health and Society, School of Population Health, University of Melbourne, Melbourne, VIC, Australia
DESIGN, SETTING AND PARTICIPANTS: A 10-year cohort study of 659 Aboriginal people who participated in population-based cardiovascular disease (CVD) risk factor surveys in 1995 and who were free of CVD at baseline, for the period from 1995 to 2004-2005 or until first CVD event. Evidence of atherosclerotic CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) was sought from hospital, primary health care and death records. PBS eligibility was assigned according to the current PBS criteria, which were amended in 2006 to include Aboriginal-specific criteria, using participants' baseline (1995) and 10-year follow-up data.
MAIN OUTCOME MEASURES: Proportions of PBS-eligible and PBS-ineligible participants who had CVD events during the study period; sensitivity and specificity of the criteria. RESULTS: Of 42 participants who had CVD events during the study period, 35 were PBS-eligible (incidence, 1130/100 000 person-years; relative risk compared with PBS-ineligible population, 4.87 [95% CI, 2.19-10.80]) and seven were PBS-ineligible. PBS eligibility was associated with older mean age (37 v 32 years) and male sex (48% v 37%), with 50.7% of participants (334/659) meeting eligibility criteria. The mean high-density lipoprotein cholesterol level at baseline was very low in both groups (0.81 v 0.87 mmol/L). The current PBS guidelines have low specificity (52%) in this population, which was found to improve (to 71%-82%) by incorporating additional non-lipid criteria (age and multiple non-lipid risk factors).
CONCLUSION: The current PBS lipid treatment criteria, which include any Aboriginal person with diabetes and less stringent cholesterol thresholds than the previous version, identify a group at very high risk of CVD. Global risk assessment may better identify those at risk.
Onemda VicHealth Koori Health Unit, Centre for Health and Society, School of Population Health, University of Melbourne, Melbourne, VIC, Australia
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