A recent perspective piece published in The American Journal of Clinical Nutrition discussed current dietary recommendations to reduce the intake of saturated fatty acids and modulate the risk of cardiovascular disease while highlighting the impact of lower saturated fatty acid intake on low-density lipoprotein cholesterol (LDL-C) and lipoprotein A.
Study: Lipoprotein(a) and Diet – A Challenge for a Role of Saturated Fat in Cardiovascular Risk Reduction? Image Credit: udra11/Shutterstock.com
Dietary modifications to modulate the risk of cardiovascular diseases are an area that has gained significant attention over the past few decades.
In addition, reducing saturated fatty acids has been proposed to lower LDL-C levels, although choosing an optimal replacement option for saturated fatty acids remains unclear.
Furthermore, recent studies have found that while reduced saturated fatty acid intake lowers LDL-C levels, there is a subsequent increase in lipoprotein A levels following these dietary changes.
Lipoprotein A contains components such as lipoprotein-associated phospholipase A2 and oxidized phospholipids (which have atherogenic properties and elevated lipoprotein A levels) that increase the risk of cardiovascular disease.
Studies also indicate that lipoprotein A plays a role in diabetes mellitus and aortic valve calcification.
Lipoprotein A and cardiovascular disease
Increasing evidence suggests that lipoprotein A is a prevalent and independent risk factor for cardiovascular disease associated with atherosclerosis, and recent guidelines have suggested interventions to reduce the elevated lipoprotein A-associated cardiovascular risk.
Although lipoprotein A levels are primarily regulated by genetic factors, a few non-genetic factors that influence lipoprotein, A levels have been identified. These are broadly categorized as lipoprotein A-increasing and lipoprotein A-decreasing factors.
The lipoprotein A-increasing factors include chronic kidney disease, hypothyroidism, growth hormones, dietary intake of saturated fatty acids, dialysis, and menopause.
A carbohydrate-deficit and saturated fatty acid-rich diet, hormone replacement therapy, hyperthyroidism, and certain liver diseases have been known to decrease lipoprotein A levels.
Although at a population level, these factors have a lower impact on lipoprotein A levels than regulation of gene expression, these dietary and metabolic factors can have a significant impact under some conditions.
Various studies have shown that while replacing saturated fatty acids with carbohydrates or monounsaturated fatty acids does lower LDL-C levels, a subsequent increase in lipoprotein A levels increases.
In a study population of African descent, a dietary replacement of saturated fatty acids with carbohydrates resulted in an approximately 10% decrease in LDL-C levels and a 24% increase in lipoprotein A levels.
Adopting a Mediterranean-style diet, which replaces most saturated fatty acids with monounsaturated fatty acids, also reported a parallel increase in lipoprotein A levels with decreasing LDL-C levels.
Markers for cardiovascular disease risk
Despite the lack of data for conclusive inferences, it appears that the risk of cardiovascular disease depends on a relative balance between the levels of the two atherogenic lipoproteins — LDL-C and lipoprotein A — and the baseline values of both in each individual.
Furthermore, while reducing cardiovascular risk due to high LDL-C levels through the modulation of saturated fatty acid intake remains important, the clinical LDL-C measurements also include the cholesterol component from lipoprotein A.
With a recent study reporting significant heterogeneity (6% to 57%) between individuals in the cholesterol content of lipoprotein-A, it is difficult to interpret the changes in LDL-C levels with certainty.
Therefore, for a precise assessment of cardiovascular disease risk, a measurement of LDL-C independent of the lipoprotein A cholesterol content or an additional assessment of the lipoprotein A cholesterol content is required.
The differential effects of lower saturated fatty acid intake on the LDL-C and lipoprotein A levels also highlight the need for increased research and better clinical practices in monitoring the effect of dietary changes.
With the high variability in lipoprotein A cholesterol levels, and the prevalence of elevated lipoprotein A levels in the population, a standard recommendation for dietary changes to reduce cardiovascular disease risk might not be generally applicable, and a more precise approach to nutritional and dietary recommendations is needed.
Overall, the evidence indicated that the standard recommendations for a heart-healthy diet which includes reduced consumption of saturated fatty acids, might have a negative impact by increasing the lipoprotein A levels despite lowering the LDL-C levels.
Since dietary changes are the most prevalent non-pharmacological form of disease prevention, tailored recommendations for dietary changes after considering individual lipid profiles might be required.
Furthermore, additional cardiac health markers such as lipoprotein A cholesterol content are necessary to assess cardiovascular disease risk accurately.
Law, H. et al. (2023) "Lipoprotein(a) and Diet – A Challenge for a Role of Saturated Fat in Cardiovascular Risk Reduction?", The American Journal of Clinical Nutrition. doi: 10.1016/j.ajcnut.2023.05.017