LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics

Tasdighi, Erfan; Adhikari, Rishav; Almaadawy, Omar; Leucker, Thorsten M.; Blaha, Michael J.

doi:10.1146/annurev-pharmtox-031023-100609

Cited by 3 publications

(1 citation statement)

References 119 publications

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“…In recent decades, the epidemiological and pathophysiological link between Lp(a) plasma levels and the risk of ASCVD has been clearly defined [30][31][32]. However, Lp(a) dosage has not been routinely suggested in clinical practice for a long time, because of the lack of therapeutic options able to significantly decrease its plasma levels [33].…”

Section: Discussionmentioning

confidence: 99%

Estimating the Prevalence and Characteristics of Patients Potentially Eligible for Lipoprotein(a)-Lowering Therapies in a Real-World Setting

Cicero,

Fogacci,

Giovannini

et al. 2023

Biomedicines

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High lipoprotein(a) (Lp(a)) plasma levels are significantly associated with an increased risk of developing atherosclerotic cardiovascular diseases (ASCVD). The aim of this analysis was to estimate the prevalence and characteristics of patients potentially eligible for Lp(a)-lowering therapies in a real-world setting (i.e., patients with ASCVD and Lp(a) levels > 70 mg/dL). For this reason, we pooled data from a large cohort of Italian outpatients (N = 5961; men: 2879, women: 3982) with dyslipidemia. A binary logistic regression analysis was used to determine the significant predictors of ASCVD in the cohort, which were age (Odds Ratio (OR): 1.158, 95% Confidence Interval (CI): 1.114 to 1.203, p < 0.001), low-density lipoprotein cholesterol at entry (OR: 1.989, 95% CI: 1.080 to 1.198, p = 0.020) and Lp(a) (OR: 1.090, 95% CI: 1.074 to 1.107, p < 0.001). In our cohort, almost half of patients with ASCVD (44.7%) may be eligible to be treated with Lp(a)-lowering agents. Interestingly, patients who do not meet the treatment criteria despite high Lp(a) (50–70 mg/dL), respectively, account for 4.7% and 7.3% of those in primary and secondary ASCVD prevention. In conclusion, in our large cohort of outpatients with dyslipidemia, the prevalence of individuals with ASCVD and very high Lp(a) plasma levels is quite high, even with a conservative estimation.

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Section: Discussionmentioning

confidence: 99%

Estimating the Prevalence and Characteristics of Patients Potentially Eligible for Lipoprotein(a)-Lowering Therapies in a Real-World Setting

Cicero,

Fogacci,

Giovannini

et al. 2023

Biomedicines

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Introduction to the Theme “Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment”

Meyer,

Amara,

Blaschke

et al. 2024

Annu. Rev. Pharmacol. Toxicol.

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The reviews in Volume 64 of the Annual Review of Pharmacology and Toxicology cover diverse topics. A common theme in many of the reviews is the interindividual variability in the clinical response to drugs. Highlighted areas include emerging developments in pharmacogenomics that can predict the personal risk for drug inefficacy and/or adverse drug reactions. Other reviews focus on the use of circulating biomarkers to define drug metabolism phenotypes and the effect of circadian regulation on drug response. Another emerging technology, digital twins that model individual patients, is used to generate computational simulations of drug effects and identify optimal personalized treatments. Another variable that may affect clinical outcomes, the nocebo response (an adverse reaction to a placebo), complicates clinical trials. These reviews further document that pharmacological individuality is an essential component of the concepts of personalized medicine and precision medicine and will likely have an important impact on patient care. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Causal Relationship between PECAM-1 Level and Cardiovascular Diseases: A Mendelian Randomization Study

Sun,

Zhong,

et al. 2024

CVIA

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Background: Platelet endothelial cell adhesion molecule (PECAM-1) is present in the vascular endothelium and plays important roles in various biological processes. Several recent studies have reported associations between PECAM-1 and certain subtypes of cardiovascular diseases (CVDs). However, further research is necessary to clarify the causal effects of PECAM-1 on CVDs. To determine whether PECAM-1 and CVDs are causally associated, we conducted a two-sample Mendelian randomization (TSMR) study. Methods: Single nucleotide polymorphisms (SNPs) associated with PECAM-1 were used as instrumental variants (IVs) to estimate the causal effects of PECAM-1 on CVDs. Six SNPs were included in our TSMR study. The inverse-variance weighted (IVW) method was applied in the primary analysis. To confirm the initial results, we conducted several complementary analyses and pleiotropy analyses. Results: In the IVW analysis, higher genetically predicted PECAM-1 levels were associated with lower risk of coronary artery disease (CAD) (OR, 0.835; CI, 0.757–0.92; P = 3 × 10−4) and myocardial infarction (MI) (OR, 0.79; CI, 0.709–0.881; P = 2.03 × 10−5). Conclusions: The findings confirmed that elevated PECAM-1 levels may decrease the risk of CAD and MI. These results confirm the causal effect of PECAM-1 on CVDs and may facilitate further investigation of the mechanism of PECAM-1 in CVD pathogenesis.

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LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics

Cited by 3 publications

References 119 publications

Estimating the Prevalence and Characteristics of Patients Potentially Eligible for Lipoprotein(a)-Lowering Therapies in a Real-World Setting

Estimating the Prevalence and Characteristics of Patients Potentially Eligible for Lipoprotein(a)-Lowering Therapies in a Real-World Setting

Introduction to the Theme “Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment”

Causal Relationship between PECAM-1 Level and Cardiovascular Diseases: A Mendelian Randomization Study

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