A comprehensive recent review clarifies the significant, genetically-driven risk posed by high Lipoprotein(a), a particle that promotes atherosclerosis and inflammation PMID:40272827. Unlike traditional risk factors like LDL cholesterol, Lp(a) levels are largely fixed from birth and resistant to diet, exercise, and other lifestyle changes. This positions Lp(a) as a critical, non-modifiable risk factor that, once identified, necessitates a more aggressive strategy for managing overall cardiovascular health. ### Key Findings Analysis of large-scale human observational and genetic data reveals the direct causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD). - **Significant Risk Increase:** Individuals with Lp(a) levels of 50 mg/dL or higher—representing the top 20% of the population—have an approximately **40% higher relative risk of ASCVD** compared to those with median levels (around 7 mg/dL) PMID:40272827. - **Quantified Event Rate:** In one large study, those with Lp(a) of 50 mg/dL or higher had about 8 heart-related events for every 100 people over ten years, compared with about 5 events for every 100 people who had low Lp(a) levels PMID:40272827. - **Genetically Determined:** Lp(a) levels are primarily set by the *LPA* gene and remain stable throughout life. Lifestyle interventions such as diet, exercise, and smoking cessation have minimal to no effect on its concentration. - **No Safe Threshold:** ASCVD risk increases continuously with rising Lp(a) levels, with no evidence of a threshold below which there is no risk. The association is independent of other major risk factors like LDL cholesterol and blood pressure. ### The Longevity Context Understanding your Lp(a) level is a cornerstone of personalized medicine and proactive longevity. While we cannot change our genes, we can change how we manage their downstream effects. Lp(a) serves as a potent 'risk intensifier'; its presence demands more rigorous control of all modifiable factors contributing to ASCVD, the leading cause of death globally. The evidence for Lp(a) as a causal factor is robust, supported by Mendelian randomization studies which use genetic variants as a natural randomized trial, confirming that lifelong higher Lp(a) directly causes ASCVD PMID:40272827. This genetic insight shifts the preventative strategy from a generalized approach to a highly individualized one. Knowing you have high Lp(a) means that achieving 'normal' levels for LDL cholesterol or blood pressure may not be sufficient. Instead, you must aim for 'optimal' levels to counteract the fixed genetic risk you carry. This principle of managing non-modifiable risk by optimizing modifiable inputs is fundamental to extending healthspan. While novel mRNA-based therapies that can lower Lp(a) by over 90% are in late-stage trials, their impact on clinical outcomes is not yet proven, making aggressive management of other factors the only current evidence-based strategy PMID:40272827. ### Actionable Protocol Given that Lp(a) is a stable, genetic risk factor, the following protocol is recommended for all adults focused on health optimization. 1. **Test Once:** Obtain a one-time Lipoprotein(a) blood test. European and Canadian guidelines recommend this for all adults at least once in their lifetime. Since levels are stable, a single test is typically sufficient. 2. **Quantify Risk:** If your level is high (defined as ≥ 50 mg/dL or ≥ 125 nmol/L), recognize this as a significant, independent, and lifelong risk factor for cardiovascular events like heart attack and stroke. 3. **Aggressively Mitigate Modifiable Risk:** In consultation with your physician, implement a strategy to minimize all other cardiovascular risk factors to counteract the risk from Lp(a): * **LDL Cholesterol/ApoB:** Target aggressively low levels, often well below standard guidelines. * **Blood Pressure:** Maintain optimal blood pressure (e.g., <120/80 mmHg). * **Lifestyle:** Adhere strictly to a heart-healthy diet (e.g., Mediterranean), maintain a healthy weight, engage in regular physical activity, and completely avoid smoking. * **Aspirin:** Consider low-dose aspirin for primary prevention *only* after a thorough discussion with your doctor to weigh the cardiovascular benefits against the increased risk of bleeding.