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What if lipoprotein (a) is increased, but the cholesterol is within normal limits?

Lp(a) is highly atherogenic and can be an independent risk factor for CVD, even if statins falsely reduce cholesterol. A dramatic decrease in triglycerides, including blood glucose regulation and diet/nutrition changes, should be investigated.

Although we do not provide specific clinical evaluations or guidance, the information below should be helpful in your assessment of the client.

Lp(a)

Please see the ODX research blog on Lp(a): https://www.optimaldx.com/research-blog/lipoprotein-biomarkers-lipoproteina

Optimal Takeaways

Lipoprotein (a) represents a group of lipoproteins comprising a molecule of Apo(a) attached to a molecule of Apo B. It is considered highly atherogenic, damaging to the vascular endothelium, and may be an independent risk factor for atherosclerosis. Elevations in Lp(a) are closely associated with increased risk of major adverse cardiac and cerebrovascular events. Low levels can be seen with malnutrition, alcoholism, and liver disease.

Although genetic factors are believed to determine Lp(a) levels, a study of newly diagnosed CVD subjects found that levels significantly decreased upon following a defined plant-based diet for four weeks. Items excluded during the study included animal products, cooked foods, oils, soda, coffee, and alcohol. Lp(a) decreased from a mean of 200.7 nmol/L at baseline, to a mean of 168.8 nmol/L after 4 weeks. Levels of total cholesterol, LDL-C, small dense LDL-C, LDL particle number, triglycerides, Apo A-1, Apo B, and markers of inflammation including hs-CRP, IL-6, fibrinogen, and white blood cells decreased significantly as well (Najjar 2018).

High lipoprotein(a) is associated with premature coronary artery disease, cerebral artery stenosis, severe hypothyroidism, uncontrolled diabetes, familial hypercholesterolemia, estrogen depletion, and chronic renal failure (Pagana 2021). Elevated Lp(a) has also been associated with major adverse cardiac and cerebrovascular events, (Mitsuda 2016), and specifically associated with increased risk of myocardial infarction, ischemic stroke (Lansted 2019), calcific aortic valve stenosis, peripheral artery disease (Tsimikas 2017), thin-cap fibroatheroma (Muramatsu 2019), heart failure, peripheral atherosclerotic stenosis, inflammation, endothelial dysfunction, and thrombosis (Madsen 2020) (ODX Lp(a)).

Additional information can be found in these resources:

Aims: Lipoprotein(a) [Lp(a)] is a causal and independent risk factor for cardiovascular disease (CVD). People with elevated Lp(a) are often prescribed statins as they also often show elevated low-density lipoprotein cholesterol (LDL-C) levels. While statins are well-established in lowering LDL-C, their effect on Lp(a) remains unclear. We evaluated the effect of statins compared to placebo on Lp(a) and the effects of different types and intensities of statin therapy on Lp(a).

Conclusion: “Statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for CVD. Our findings suggest that in these patients, statin therapy will not change Lp(a)-associated CVD risk” (de Boer 2022).

Aims: Lipoprotein(a) [Lp(a)] is elevated in 20-30% of people. This study aimed to assess the effect of statins on Lp(a) levels.

Conclusion: This meta-analysis reveals that statins significantly increase plasma Lp(a) levels. Elevations of Lp(a) post-statin therapy should be studied for effects on residual cardiovascular risk. (Tsimikas 2020).

Triglycerides

The dramatic decrease in triglycerides from 130 to 50 mg/dL (now below optimal) should be evaluated further, including the potential causes of such a decrease, and whether elevated blood glucose contributed to the initial higher level.

Please see the ODX research blog articles on ODX Triglycerides: https://www.optimaldx.com/research-blog/lipid-biomarkers-triglycerides

and ODX TyG Index:

https://www.optimaldx.com/research-blog/blood-glucose-regulation-biomarkers-triglyceride-glucose-index

Optimal Takeaways

Triglycerides are concentrated form of fat found in the diet, in adipose tissue, and circulating in the blood. They are composed of a glycerol backbone attached in different combinations to three fatty acid types that include monounsaturated, polyunsaturated, and saturated. Triglycerides increase after a meal but should return to normal fairly quickly.

Persistently elevated triglycerides are a sign of metabolic dysfunction and are associated with obesity, CVD, metabolic syndrome, mitochondrial dysfunction, and pancreatitis. Low triglycerides in the blood can be associated with poor absorption, inadequate intake, and hyperthyroidism.

Low triglycerides are associated with malabsorption, malnutrition, and hyperthyroidism. Drugs that may decrease triglycerides include asparaginase, fibrates, clofibrate, colestipol, and statins, as well as ascorbic acid (Pagana 2021).  

References


de Boer, Lotte M et al. “Statin therapy and lipoprotein(a) levels: a systematic review and meta-analysis.” European journal of preventive cardiology vol. 29,5 (2022): 779-792. doi:10.1093/eurjpc/zwab171 https://academic.oup.com/eurjpc/article/29/5/779/6439180?login=false

Tsimikas, Sotirios et al. “Statin therapy increases lipoprotein(a) levels.” European heart journal vol. 41,24 (2020): 2275-2284. doi:10.1093/eurheartj/ehz310 https://academic.oup.com/eurheartj/article/41/24/2275/5492355