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PostPosted: 08 Dec 2020 03:05 
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Published:November 10, 2020DOI:https://doi.org/10.1016/S0140-6736(20)32332-1
Gencer et al

Elevated LDL cholesterol and increased risk of myocardial …
Summary

The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients.
Methods

In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2015, and Aug 14, 2020, without any language restrictions. We included randomised controlled trials of cardiovascular outcomes of an LDL cholesterol-lowering drug recommended by the 2018 American College of Cardiology and American Heart Association guidelines, with a median follow-up of at least 2 years and data on older patients (aged ≥75 years).
We excluded trials that exclusively enrolled participants with heart failure or on dialysis because guidelines do not recommend lipid-lowering therapy in such patients who do not have another indication. We extracted data for older patients using a standardised data form for aggregated study-level data.
We meta-analysed the risk ratio (RR) for major vascular events (a composite of cardiovascular death, myocardial infarction or other acute coronary syndrome, stroke, or coronary revascularisation) per 1 mmol/L reduction in LDL cholesterol.
Findings

Data from six articles were included in the systematic review and meta-analysis, which included 24 trials from the Cholesterol Treatment Trialists' Collaboration meta-analysis plus five individual trials.
Among 244 090 patients from 29 trials, 21 492 (8·8%) were aged at least 75 years, of whom 11 750 (54·7%) were from statin trials, 6209 (28·9%) from ezetimibe trials, and 3533 (16·4%) from PCSK9 inhibitor trials.
Median follow-up ranged from 2·2 years to 6·0 years. LDL cholesterol lowering significantly reduced the risk of major vascular events (n=3519) in older patients by 26% per 1 mmol/L reduction in LDL cholesterol (RR 0·74 [95% CI 0·61–0·89]; p=0·0019), with no statistically significant difference with the risk reduction in patients younger than 75 years (0·85 [0·78–0·92]; pinteraction=0·37).

Among older patients, RRs were not statistically different for statin (0·82 [0·73–0·91]) and non-statin treatment (0·67 [0·47–0·95]; pinteraction=0·64). The benefit of LDL cholesterol lowering in older patients was observed for each component of the composite, including cardiovascular death (0·85 [0·74–0·98]), myocardial infarction (0·80 [0·71–0·90]), stroke (0·73 [0·61–0·87]), and coronary revascularisation (0·80 [0·66–0·96]).
Interpretation

In patients aged 75 years and older, lipid lowering was as effective in reducing cardiovascular events as it was in patients younger than 75 years. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients.


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PostPosted: 05 Jan 2021 14:27 
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Hi Mohan
Though it is a well-known fact that lowering of LDL has a definite positive effect on the cardiovascular disease profile, the present study which you have posted further confirms the earlier findings. But when one deals with a lipid profile, we hardly talk about Triglycerides. It is an established fact that the relationship of TG to MI risk is independent of LDL-C levels. That means even if the LDL has come down to the targeted level, cardiovascular risk is still there if the triglycerides remain at higher level. This is so even though it is established that triglycerides do not contribute directly to the plaque formation. Compared with cholesterol, TG is readily metabolized to free fatty acids which apart from being a source of energy, also activates proinflammatory pathways which possibly contribute to insulin resistance and atherogenicity. Data from randomized trials have consistently shown that individuals with mixed hyperlipidaemia (defined as Lipid Triad --elevated LDL-C, elevated TG and low HDL-C) carried the highest risk of CHD events. It has been repeatedly shown in various studies that increased levels TGs are associated with increased mortality. It has been noted that those who had high TG and a low HDL-C had more CHD events and stroke than those with normal TG and normal HDL-C levels. The plasma TG level represents the concentration of TG-rich VLDL. In addition, hypertriglyceridemia produces changes in composition of LDL and HDL particles. The large buoyant LDL does not usually penetrate arterial walls but TG treated LDL becomes small and dense which easily penetrates and causes atherosclerosis, thus TG concentration produces a shift LDL from a safe subclass pattern to another lethal pattern. The HDL cholesterol is known to be anti-atherosclerotic in that they remove the fat from artery level to liver where they are metabolised. But the TG enriched HDL becomes less efficient in reverse cholesterol transport via scavenger receptors. (j.Biol chem 2001; 276-480)

TG stimulates the production of proinflammatory cytokines, fibrinogen and coagulation factors and impairs fibrinolysis. So, it can be concluded that a combination of TG and elevated LDL contributes to elevated CHD risk than an elevated LDL alone.

UA Mohammed


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PostPosted: 10 Jan 2021 03:11 
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excellent explanation dear Mohammed.

best reagards.


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