Non-HDL may be linked to ASCVD risk
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Non-HDL was strongly linked to long-term risk for atherosclerotic CVD, as shown by a tool for long-term risk assessment, according to a study published in The Lancet.
“Our estimates suggest that halving non-HDL cholesterol levels may be associated with reduced risk of cardiovascular events by the age of 75 years, and that this reduction in risk is larger the sooner cholesterol levels are reduced,” Stefan Blankenberg, MD, professor at the German Center for Cardiovascular Research in Berlin, said in a press release. “The risk scores currently used in the clinic to decide whether a person should have lipid-lowering treatment only assess the risk of cardiovascular disease over 10 years, and so may underestimate lifetime risk, particularly in young people.”
Multinational Cardiovascular Risk Consortium data
Fabian J. Brunner, MD, consultant and scientific assistant at University Heart and Vascular Center Hamburg in Germany, and colleagues analyzed data from 398,846 patients (median age, 51 years; 49% women) from the Multinational Cardiovascular Risk Consortium free from prevalent CVD at baseline, which was defined as a history of CABG, MI, ischemic or hemorrhagic stroke, or PTA.
A derivation (n = 91,786; 48% women) and validation design (n = 199,431; 49% women) were utilized to create an estimation tool to measure the likelihood of a CVD event by age 75 years. This tool was dependent on sex, age and risk factors, in addition to a modeled risk reduction based on a 50% reduction in non-HDL.
The primary composite endpoint was the occurrence of first nonfatal or fatal CHD or ischemic stroke event.
During a median follow-up of 13.5 years, there were 54,542 CVD endpoints.
Based on incidence curve analyses, there were progressively higher 30-year CVD event rates as non-HDL increased. For women, this ranged from 7.7% for non-HDL less than 2.6 mmol/L to 33.7% for non-HDL of 5.7 mmol/L or greater (P < .0001). This was also seen in men, which ranged from 12.8% to 43.6% in the aforementioned non-HDL ranges (P < .0001).
Compared with a non-HDL less than 2.6 mmol/L, there was an increase in CVD with non-HDL between 2.6 mmol/L and less than 3.7 mmol/L (HR = 1.1; 95% CI, 1-1.3) and for levels of 5.7 mmol/L and greater (HR = 1.9; 95% CI, 1.6-2.2) for women. This association was also seen in men with non-HDL between 2.6 mmol/L and less than 3.7 mmol/L (HR = 1.1; 95% CI, 1-1.3) and with levels greater of 5.7 mmol/L or greater (HR = 2.3; 95% CI, 2-2.5).
The tool was effective in estimating CVD event probabilities for non-HDL, and was comparable among the derivation and validation cohorts. The root-mean-square error was lower than 1% for estimates of CVD probability.
The risk for a CVD event was reduced with a 50% reduction in non-HDL concentration, which was greater in patients whose cholesterol concentrations were reduced earlier in the study.
“In young individuals, the long-term risk of cardiovascular disease should constitute the basis of primary prevention,” Brunner and colleagues wrote. “Since the risk factor burden is incorporated as a categorical variable in our model, we cannot provide a weighting among the different risk factors or a quantitative consideration of every single risk factor as do other risk models. Instead, because of its simplicity, our risk circle tool provides an opportunity to estimate lifetime risks based on non-HDL cholesterol in an accessible and easily understood way that can improve physician-patient communication about preventive strategies in clinical practice.”
Potential implications
In a related editorial, Jennifer G. Robinson, MD, professor and director of the Preventive Intervention Center at The University of Iowa College of Public Health in Iowa City, wrote: “The tool developed from the analysis by Brunner and colleagues could facilitate shared decision-making in primary prevention by estimating lifetime risk of atherosclerotic cardiovascular disease up to 75 years of age, as well as the potential for individualized benefit from lowering non-HDL cholesterol or LDL cholesterol concentrations over a lifetime. The investigators should develop an online calculator in addition to the risk circle tools in their article that could facilitate the widespread incorporation of their recommendations into future guidelines for cholesterol lowering in European-ancestry populations.” – by Darlene Dobkowski
Disclosures: Blankenberg reports he received grants from Abbott Laboratories, Bayer, Siemens, Singulex and ThermoFisher Scientific and personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, Medtronic, Pfizer, Roche, Siemens and ThermoFisher Scientific. Brunner reports he received grants from the ASPIRE Cardiovascular grant award, Pfizer. Robinson reports she received grants to her institution from Acasti, Amarin, AstraZeneca, Eisai, Eli Lilly, Esperion, GlaxoSmithKline, The Medicines Company, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron and Sanofi. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Salim S. Virani, MD, PhD, FACC, FAHA
It is well known that non-HDL cholesterol is one of the most important lipid parameters associated with future risk of atherosclerotic CV events as shown in many prior studies. This study extends out the results in primary prevention to a much longer follow-up than what is available from prior studies. Importantly, the study shows that in younger individuals, even modest elevation in non-HDL cholesterol is associated with a much higher risk than older adults.
This has two implications. First, this highlights the importance of primary and primordial prevention at an early age. Second, this highlights the limitations of our current risk estimation algorithms, which mostly assess 10-year ASCVD risk. These results highlight the need to look beyond 10-year and more into 30 years or lifetime ASCVD risk, especially for younger individuals. Even modest elevation in atherogenic lipoproteins (or the cholesterol content of these lipoproteins) over a longer duration can be very harmful at the population level.
Most guidelines already talk about non-HDL cholesterol. What is needed is how to get this information in the hands of practicing clinicians. Some of our prior work has shown that only two-thirds of the clinicians know that non-HDL cholesterol levels can actually be calculated from a standard lipid panel, and about half of the clinicians can calculate non-HDL cholesterol levels when given a lipid panel result. Therefore, clinicians need tools to allow them to better understand what non-HDL cholesterol is and how to calculate it. In that respect, direct reporting of non-HDL cholesterol level results on standard lipid panels (as done by some laboratories) is a welcome change.
Research is needed on how best to provide this information to the clinicians at the point of care.
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