LDL Not the Primary Culprit?
Batya Swift Yasgur, MA, LSW
Two new research recommend that low-density lipoprotein LDL cholesterol (LDL-C) perhaps now no longer the primary motive force of atherosclerotic cardiovascular ailment (ASCVD).
The findings in place of implicating remnant LDL cholesterol (remnant-C) and very-low-density lipoprotein (VLDL) LDL cholesterol withinside the improvement of cardiovascular ailment (CVD) and myocardial infarction (MI).
The PREDIMED take a look at, carried out in Spain, tested the affiliation of triglycerides and remnant-C with essential cardiovascular events (MACE) in older people with excessive CVD threat.
It determined that tiers of triglycerides and remnant-C have been related to MACE independently of different threat elements. However, there has been no comparable affiliation with LDL-C.
“These findings lead [clinicians] to do not forget withinside the medical control of dyslipidemias a more manage of the lipid profiles as a whole, along with remnant-LDL cholesterol and/or triglycerides,” Montserrat Fitó Colomer, MD, Ph.D., of the Cardiovascular Risk and Nutrition Research Group, Hospital del Mar Medical Research Institute, Barcelona, Spain, advised theheart.org | Medscape Cardiology.
In a separate analysis, the Copenhagen General Population Study, which centered on 25,000 those now no longer taking the lipid-reducing remedy, check out the position of VLDL and triglycerides in using MI threat from apolipoprotein B (apo B)-containing lipoproteins.
“Elevated VLDL LDL cholesterol defined a bigger fraction of threat than did multiply LDL LDL cholesterol, or multiplied VLDL triglycerides,” Børge G. Nordestgaard, MD, DMSc, professor, University of Copenhagen, Denmark, advised theheart.org | Medscape Cardiology.
Both types of research were posted online on November 30 withinside the Journal of the American College of Cardiology. But in an article accompanying each report, John Burnett, MD, Ph.D., from the University of Western Australia in Perth, and co-workers suggested that it’d be “untimely to discard LDL-C primarily based totally on PREDIMED.”
The findings are “inadequate to offset the mountain of actually loads of research that uphold the price of LDL-C in prediction and intervention of ASCVD,” Burnett and coauthors write. Similarly, the editorialists suggested that even though the findings from the take a look at via way of means of Nordestgaard and co-workers imply that VLDL LDL cholesterol is the “new youngster on the town for prediction, LDL LDL cholesterol keeps predictive power.” Clinical cardiologists ought to now no longer “shelve LDL LDL cholesterol and include VLDL and remnant LDL cholesterol as the brand new oracles of ASCVD threat.” Commenting for theheart.org | Medscape Cardiology, Burnett stated, “The take-domestic message for clinicians in each paper is that LDL-C is the primary lipid size to manual medical decisions; however, the residual threat of atherosclerotic cardiovascular ailment remains, even after LCL-C is treated. “Assessment of residual ASCVD threat with nontraditional lipid biomarkers, along with VLDL LDL cholesterol and remnant LDL cholesterol, in addition to lipoprotein (a) and apoB, may also enhance prognostication and assist manual preventive treatments,” he added.
“Affordable and Inexpensive”
In their report, the PREDIMED take a look at authors to explain that atherogenic dyslipidemia is characterized via way of means of “an extra of serum triglycerides” contained in VLDL, intermediate-density lipoproteins, and their remnants, all of which might be called “triglyceride-wealthy lipoproteins (TRLs).”
TRLs and remnant-C “have the potential to go the arterial wall” and might consequently play a causal position in atherosclerosis improvement, they write. The principal PREDIMED trial compared a low-fat food plan with the Mediterranean Diet to prevent CVD in excessive–threat contributors.
Those enrolled withinside the trial “had an excessive incidence of diabetes, obesity, and metabolic syndrome, situations which are related to insulin resistance, hypertriglyceridemia, and atherogenic dyslipidemia,” the cutting-edge authors write. “Thus, this cohort of topics at excessive cardiovascular threat changed into properly ideal for researching the affiliation of triglycerides and TRLs with cardiovascular outcomes.”
The researchers investigated the position of triglycerides and remnant-C in incident CVD amongst those excessive–threat people, mainly people with continual cardiometabolic disorders (pre-diabetes, kind 2 diabetes, and poorly managed diabetes); obese and obesity; metabolic syndrome; and renal failure.
Their 6901 contributors (42.6% male, suggest age sixty-seven years, suggest BMI 30. zero kg/m2) had an analysis of kind 2 diabetes or ≥three CVD threat elements along with cutting-edge smoking, hypertension, multiplied LDL-C tiers, low HDL-C tiers, multiplied BMI, or own circle of relatives records of an untimely coronary heart ailment. The number one looks at the endpoint changed into a composite of damaging cardiovascular events (MACE): MI, stroke, or cardiovascular death.
Participants have been accompanied for an average of 4. eight years, for the duration of which there has been a complete of 263 MACE events. Multivariable-adjusted analyses confirmed that tiers of triglycerides and remnant-C had been each related to MACE unbiased of different threat elements (HR, 1.04; 95% CI, 1.02 – 1.06; and HR, 1.21; 95% CI, 1.10 – 1.33 in keeping with 10 mg/dl, respectively, each P < .001). Non-HDL-C changed into additionally related to MACE (HR, 1.05; 95% CI, 1.01 – 1.10 in keeping with 10 mg/dl, P = .026).
In particular, multiplied remnant-C (≥ 30 mg/dL), compared with decreased concentrations, flagged topics at a better threat of MACE, even though their LDL-C tiers have been at target (described as ≤ one hundred mg/dL). Levels of LDL-C and HDL-C have now been no longer related to MACE. “The oblique calculation of remnant-C is a low-cost and cheaper method, that could offer precious information for medical control,” Fitó Colomer stated. “The outcomes of this take a look at recommending that during people at excessive cardiovascular threat with properly–managed LDL-C, triglycerides and in particular remnant-C ought to be taken into consideration as a remedy target,” she proposed.
New Oracles?
Nordestgaard stated their take a look at changed into encouraged via way of means of attention that “in medical practice, the point of interest for lipid-associated threat is sort of totally at the discount of LDL-C for prevention of ASCVD,” so the cutting-edge awareness wishes to be reevaluated due to the fact sufferers with low LDL-C however multiplied VLDL-C and plasma triglycerides “won’t be supplied good enough preventive lipid-reducing remedy as a way to save you destiny MI and ASCVD.”
His group, consequently, examined the speculation that VLDL-C and triglycerides may also explain a part of the MI threat from apoB-containing lipoproteins. They used measurements of plasma apoB and LDL cholesterol and triglyceride content material of VLDL-C, intermediate-density lipoprotein LDL cholesterol (IDL-C), and LDL-C withinside the take a look at contributors (N = 25,480, median age sixty-one years, 53�male), who have been required to be freed from MI and now no longer receiving lipid-reducing remedy at baseline. During a mean 11-yr follow-up period, 1816 contributors skilled an MI.
They tended to be older than folks who now no longer enjoy an MI and are much more likely to be male, smoke, and have better systolic blood pressure. Each 39-mg/dL growth in lipid degree changed determined to be related to better MI threat.
Table. The risk for myocardial infarction by lipid fraction
| Lipid fraction | Adjusted HR (95% CI) with each 39 mg/dL increase |
|---|---|
| VLDL cholesterol | 2.07 (1.81 – 2.36) |
| VLDL triglycerides | 1.19 (1.14 – 1.25) |
| IDL cholesterol | 5.38 (3.73 – 7.75) |
| LDL cholesterol | 1.86 (1.62 – 2.14) |
The researchers checked out the MI-related threat of particular subfractions of apoB-containing lipoproteins.
“VLDL LDL cholesterol defined 1/2 of the MI threat from multiplied apoB-containing lipoproteins, and IDL and LDL-C collectively accounted for the handiest 29% of the threat,” Nordestgaard stated.
“If LDL LDL cholesterol is sufficiently reduced, clinicians want to assess viable multiplied triglyceride-wealthy lipoproteins, both as multiplied plasma triglycerides, remnant LDL cholesterol, or multiplied VLDL LDL cholesterol; and, if multiplied, attention ought to additionally accept to the discount of triglyceride-wealthy lipoproteins,” he advised.
The Copenhagen General Population looks at changes into funded via way of means of the Danish Heart Foundation and the Novo Nordisk Foundation. Nordestgaard discloses consulting for AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Kowa, Denka Seiken, Amarin, Novartis, Novo Nordisk, and Silence Therapy; disclosures for the alternative authors are withinside the report.
PREDIMED changed into supported via way of means of offers from the Instituto de Salud Carlos III- FEDER, Fundació La Marató de TV3, and Agència de Gestió d’Ajuts Universitaris i de Recerca.
Fitó Colomer has disclosed no applicable economic relationships; disclosures for the coauthors are withinside the report. Burnett has disclosed no applicable economic relationships; disclosures for the alternative editorialists are withinside the authentic article. J Am Coll Cardiol. Published online November 30, 2020
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