Eddy Edson
Well-Known Member
- Relationship to Diabetes
- Type 2
A pretty impressive summary of the evidence to date on how LDL acts to screw up arteries: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz962/5735221
Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel
Atherosclerotic cardiovascular disease (ASCVD) starts early, even in childhood.1,2 Non-invasive imaging in the PESA (Progression of Early Subclinical Atherosclerosis) study revealed that 71% and 43% of middle-aged men and women, respectively, have evidence of subclinical atherosclerosis.3 Extensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that low-density lipoprotein (LDL) is causal in this process, as summarized in the first Consensus Statement on this topic.4 What are the key biological mechanisms, however, that underlie the central role of LDL in the complex pathophysiology of ASCVD, a chronic and multifaceted lifelong disease process, ultimately culminating in an atherothrombotic event?
....
Extensive evidence on the pathophysiology of ASCVD presented here supplements and extends our earlier review on the causality of LDL based on epidemiological, GWAS, and Mendelian randomization studies, as well as controlled intervention trials with pharmacological agents targeting the LDL receptor.4 Such evidence, together with the associated molecular mechanisms, has clear implications across the continuum of ASCVD prevention (i.e. primordial, primary, secondary, and tertiary) and is consistent with the central concept derived from genomics that the cumulative arterial burden of LDL-C drives the development and progression of ASCVD and its clinical sequelae.4,334,335
Furthermore, the pathophysiological evidence supports therapeutic strategies aimed at maintaining very low levels of LDL-C (e.g. <1 mmol/L or 40 mg/dL) in patients with established ASCVD at very high risk of recurrent events.336 Such low plasma LDL-C levels are now attainable with the combination of statins and PCSK9 inhibitors (with or without addition of ezetimibe), therapeutic regimens that have proven safety and tolerability.273,337,338 The unequivocal body of evidence for LDL causality in ASCVD will impact on future international recommendations for the management of atherogenic and ASCVD-promoting dyslipidaemias and will guide the rational use of both existing and new therapies.339–342 The success of modern programmes of ASCVD prevention will also rely on the practice of precision medicine and patient-centred approaches.343
Finally, this thesis has highlighted emerging mechanistic features of atherosclerosis that can potentially lead to evaluation of new therapeutic targets integral to arterial wall biology and plaque stability. Prominent amongst these are endothelial transcytosis of atherogenic lipoproteins, monocyte/macrophage and SMC biology, efferocytosis, inflammation, innate and adaptive immune responses to the intimal retention of apoB-containing lipoproteins and calcification (Take home figure). The future holds great promise but will not be lacking in surprises.
My note: This supports my now-achieved goal of getting my LDL down to 0.7 mmol/L, which is not surprising given that it uses the same studies on which I based that goal.
It's maybe a bit interesting that I got down to that very low level without needing one of the new, powerful and expensive PCSK9 inhibitor drugs or ezetimibe, just max dosage statin. I eat a large amount of fibre, 70g+ per day, which probably has at least something to do with that.
Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel
Atherosclerotic cardiovascular disease (ASCVD) starts early, even in childhood.1,2 Non-invasive imaging in the PESA (Progression of Early Subclinical Atherosclerosis) study revealed that 71% and 43% of middle-aged men and women, respectively, have evidence of subclinical atherosclerosis.3 Extensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that low-density lipoprotein (LDL) is causal in this process, as summarized in the first Consensus Statement on this topic.4 What are the key biological mechanisms, however, that underlie the central role of LDL in the complex pathophysiology of ASCVD, a chronic and multifaceted lifelong disease process, ultimately culminating in an atherothrombotic event?
....
Extensive evidence on the pathophysiology of ASCVD presented here supplements and extends our earlier review on the causality of LDL based on epidemiological, GWAS, and Mendelian randomization studies, as well as controlled intervention trials with pharmacological agents targeting the LDL receptor.4 Such evidence, together with the associated molecular mechanisms, has clear implications across the continuum of ASCVD prevention (i.e. primordial, primary, secondary, and tertiary) and is consistent with the central concept derived from genomics that the cumulative arterial burden of LDL-C drives the development and progression of ASCVD and its clinical sequelae.4,334,335
Furthermore, the pathophysiological evidence supports therapeutic strategies aimed at maintaining very low levels of LDL-C (e.g. <1 mmol/L or 40 mg/dL) in patients with established ASCVD at very high risk of recurrent events.336 Such low plasma LDL-C levels are now attainable with the combination of statins and PCSK9 inhibitors (with or without addition of ezetimibe), therapeutic regimens that have proven safety and tolerability.273,337,338 The unequivocal body of evidence for LDL causality in ASCVD will impact on future international recommendations for the management of atherogenic and ASCVD-promoting dyslipidaemias and will guide the rational use of both existing and new therapies.339–342 The success of modern programmes of ASCVD prevention will also rely on the practice of precision medicine and patient-centred approaches.343
Finally, this thesis has highlighted emerging mechanistic features of atherosclerosis that can potentially lead to evaluation of new therapeutic targets integral to arterial wall biology and plaque stability. Prominent amongst these are endothelial transcytosis of atherogenic lipoproteins, monocyte/macrophage and SMC biology, efferocytosis, inflammation, innate and adaptive immune responses to the intimal retention of apoB-containing lipoproteins and calcification (Take home figure). The future holds great promise but will not be lacking in surprises.
My note: This supports my now-achieved goal of getting my LDL down to 0.7 mmol/L, which is not surprising given that it uses the same studies on which I based that goal.
It's maybe a bit interesting that I got down to that very low level without needing one of the new, powerful and expensive PCSK9 inhibitor drugs or ezetimibe, just max dosage statin. I eat a large amount of fibre, 70g+ per day, which probably has at least something to do with that.