In FH, Lp(a) levels comparable to LDL in risk for premature poor outcomes
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Lipoprotein(a) levels of 67 mg/dL or more may be indicative of similar risk for premature MI as LDL of 180 mg/dL or more in patients with familial hypercholesterolemia, researchers reported.
In addition, in familial hypercholesterolemia (FH), Lp(a) of 130 mg/dL or more may also indicate similar atherosclerotic CVD risk as LDL of 175 mg/dL, according to a study published in the Journal of the American College of Cardiology.
“The 2019 European, 2020 Indian, 2021 Canadian, and 2021 Chinese lipid guidelines recommend that plasma lipoprotein(a) should be measured once in an adult’s lifetime to identify individuals at genetically high risk of ASCVD,” Berit Storgaard Hedegaard, RN, of the department of cardiology at Viborg Regional Hospital, Regional Hospital Central Jutland in Viborg, Denmark, and colleagues wrote. “The present direct comparison of conventionally diagnosed elevated plasma lipoprotein(a) with clinical and genetic FH in the same population provides for the first time the levels of plasma lipoprotein(a) that are equivalent to LDL cholesterol in FH on risk of MI and ASCVD.”
Researchers in Denmark utilized data from the Copenhagen General Population Study to ascertain the Lp(a) level equivalent to the LDL level in clinical and genetic FH associated with risk for MI and ASCVD.
Lipid levels were measured using blood samples drawn in the non-fasting state.
Lipid levels indicative of MI and ASCVD risk were defined using several metrics, including Make Early Diagnosis to Prevent Early Death (MEDPED), Simon Broome criteria and the Dutch Lipid Clinic Network (DLCN).
Lp(a) level comparable to LDL in FH for CVD risk
The analysis included 69,644 patients with FH who were followed for 42 years, during which time, 4,166 had MI and 11,464 developed ASCVD.
Researchers found that, in patients with FH, a plasma Lp(a) level of 67 mg/dL to 402 mg/dL was equivalent to an LDL of 180 mg/dL in risk for MI, whereas a Lp(a) level of 130 mg/dL to 391 mg/dL was equivalent to an LDL of 175 mg/dL in risk for ASCVD.
Moreover, people with both elevated Lp(a) and either FH or a family history of premature MI had greater risk for MI and ASCVD compared with those with either genetic risk factor alone, according to the study. In people with either FH or a family history of premature MI, those with Lp(a) in the upper 20% had the highest risk for MI (HR = 14; 95% CI, 9.15-21.3) and ASCVD (HR = 5.05; 95% CI, 3.41-7.48) compared with those with Lp(a) in the lower 50% ( 10 mg/dL).
“The present study also found that the risk of MI and ASCVD were highest in individuals with both FH and elevated lipoprotein(a), in accordance with previous studies,” the researchers wrote. “This emphasizes the importance of measuring lipoprotein(a) in patients with FH as well as the importance of evaluating patients with elevated lipoprotein(a) for FH.”
Actual LDL ‘most robust’ measure of CV risk
In a related editorial, Pamela B. Morris, MD, FACC, FAHA, FASPC, FNLA, director of preventive cardiology, co-director of women’s heart care at the Medical University of South Carolina, and colleagues discussed the use of Lp(a) in assessing CV risk alongside periodic lipid panels.
“Ultimately, the most robust measurement appears to be the actual LDL-C level, irrespective of the clinical diagnosis, particularly because this is the main driver of risk, rather than the underlying FH genetics. Perhaps a more robust analysis in understanding the relative risk of FH and Lp(a) is to consider comparison of risk by similar changes in LDL-C and Lp(a),” Morris and colleagues wrote. “The weight of evidence strongly supports that both genetic lipid disorders, elevated Lp(a) levels and FH, are causally associated with an increased risk of premature ASCVD and should be carefully considered in risk assessment and management for ASCVD risk reduction. In addition to performing a lipid panel periodically according to evidence-based guidelines, measurement of Lp(a) levels should also be performed at least once in an individual’s lifetime for ASCVD risk assessment.”
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