Elevated plasma lipoprotein(a) [Lp(a)] is a causal risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, commonly used ASCVD clinical risk-assessment tools in pri Show more
Elevated plasma lipoprotein(a) [Lp(a)] is a causal risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, commonly used ASCVD clinical risk-assessment tools in primary care do not include the measurement of Lp(a) levels, potentially under-estimating individual risk. Here we describe the case of a late-40s, asymptomatic, normotensive, non-smoking veteran athlete with a moderately raised low density lipoprotein cholesterol (LDL-C) level and a calculated 10-year QRISK3 score of 4.1%. Despite his low calculated QRISK3 score, significantly elevated Lp(a) levels led to advanced cardiovascular imaging, which revealed severe stenosis (75%, CAD-RADS 4A) of the left anterior descending coronary artery. This case demonstrates the limitations of conventional cardiovascular risk tools and highlights the importance of Lp(a) measurement for identifying and managing high-risk patients. Show less
Lipoprotein(a) [Lp(a)] is a well recognised contributor in the development of cardiovascular disease. Unlike other lipoproteins, Lp(a) levels are primarily genetically determined, and in most individu Show more
Lipoprotein(a) [Lp(a)] is a well recognised contributor in the development of cardiovascular disease. Unlike other lipoproteins, Lp(a) levels are primarily genetically determined, and in most individuals remain largely stable throughout life. Elevated Lp(a) is common in the general population, and various international guidelines now recommend at least one lifetime measurement of Lp(a) and its inclusion into an individual's cardiovascular risk assessment. Despite this, Lp(a) is still rarely measured, even in patients with known cardiovascular risk factors. Critically, the therapeutic landscape for Lp(a)-lowering medications is rapidly evolving with multiple drugs showing considerable promise in late-stage clinical trials. The strength and consistency of the evidence now cement Lp(a) as an essential biomarker of cardiovascular health. Failure to incorporate measurement of Lp(a) into clinical practice will continue to underestimate an individual's risk of CVD. Now is the time for Lp(a) to move from a neglected biomarker to a widely known and measured essential component of cardiovascular risk assessment. Show less
Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipopr Show more
Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease. Show less