Mechanisms
Oral hormone therapy lowers Lp(a) more than transdermal, and kidney disease raises it while liver disease lowers it, a review of non-genetic influences (Atherosclerosis 2022)
Original title: Non-genetic influences on lipoprotein(a) concentrations
This review by Enkhmaa and Berglund surveys non-genetic factors that influence Lp(a) levels beyond the strong genetic control already established, covering diet, physical activity, hormones and pathological conditions. Randomised trials show diets lower in saturated fat modestly influence Lp(a), often in the opposite direction to LDL cholesterol, while exercise studies show inconsistent effects depending on age, intensity and duration. Hormone replacement therapy lowers Lp(a) in postmenopausal women, with oral oestradiol more effective than transdermal, regardless of hormone type, dose or added progestogen. Kidney disease markedly raises Lp(a), depending on disease stage, dialysis modality and apo(a) phenotype, while liver disease lowers Lp(a) as it progresses, though population studies on non-alcoholic fatty liver disease specifically remain conflicting. The findings support a meaningful, modifiable role for diet, hormones and organ disease alongside genetics in shaping individual Lp(a) levels.
Original abstract
An elevated level of lipoprotein(a) [Lp(a)] is a genetically regulated, independent, causal risk factor for cardiovascular disease. However, the extensive variability in Lp(a) levels between individuals and population groups cannot be fully explained by genetic factors, emphasizing a potential role for non-genetic factors. In this review, we provide an overview of current evidence on non-genetic factors influencing Lp(a) levels with a particular focus on diet, physical activity, hormones and certain pathological conditions. Findings from randomized controlled clinical trials show that diets lower in saturated fats modestly influence Lp(a) levels and often in the opposing direction to LDL cholesterol. Results from studies on physical activity/exercise have been inconsistent, ranging from no to minimal or moderate change in Lp(a) levels, potentially modulated by age and the type, intensity, and duration of exercise modality. Hormone replacement therapy (HRT) in postmenopausal women lowers Lp(a) levels with oral being more effective than transdermal estradiol; the type of HRT, dose of estrogen and addition of progestogen do not modify the Lp(a)-lowering effect of HRT. Kidney diseases result in marked elevations in Lp(a) levels, albeit dependent on disease stages, dialysis modalities and apolipoprotein(a) phenotypes. In contrast, Lp(a) levels are reduced in liver diseases in parallel with the disease progression, although population studies have yielded conflicting results on the associations between Lp(a) levels and non-alcoholic fatty liver disease. Overall, current evidence supports a role for diet, hormones and related conditions, and liver and kidney diseases in modifying Lp(a) levels.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.