Measuring apoB levels is a more accurate indicator of cardiovascular disease risk than traditional measurements like LDL-C.
Non-HDL-C and HDL-C alone do not provide a complete picture of cardiovascular disease risk, and lipid levels may overlook crucial factors that contribute to disease development.
Hypertension and smoking are significant factors in cardiovascular disease risk, although the direct link to atherosclerosis is not fully understood.
Coronary artery calcium scores should be interpreted in conjunction with other risk factors to make informed treatment decisions, as their usefulness varies based on age and other factors.
Deep dives
The importance of p o b in predicting risk of athroscrosis
Measuring a person's apo b (p o b) level, which represents the total number of atherogenic particles in the blood, is a more accurate indicator of cardiovascular disease risk than traditional measurements like l d l c. People with high p o b levels are at a higher risk of heart attacks and strokes. The number of atherogenic particles is a more significant factor than individual lipid levels when it comes to predicting risk. Mendelian randomization studies have also shown p o b to be a causal factor in atherosclerosis, further supporting its importance in risk assessment.
The limitations of using non h d l clestral and h d l clestral as risk indicators
While non h d l c and h d l c are commonly used to assess cardiovascular disease risk, they do not provide a complete picture. Non h d l c does not account for the total number of atherogenic particles, while h d l c has been shown to be less predictive. Treating patients based solely on these measurements may not accurately address their risk. Additionally, the complexity of lipoprotein phenotypes can make risk assessment challenging, and relying solely on lipid levels may overlook crucial factors that contribute to disease development.
The impact of hypertension and smoking on cardiovascular risk
Hypertension and smoking are both significant factors in cardiovascular disease risk. However, the direct link between these factors and atherosclerosis is not fully understood. Hypertension, in particular, plays a role in the development of arterial stiffness and increased pressure within the arterial wall. Smoking, on the other hand, raises overall risk and may exacerbate the trapping of atherogenic particles within the arterial wall. While these factors are important to consider in risk assessment, they should not override the assessment of other crucial indicators like p o b levels.
The role and limitations of coronary artery calcium scores
Coronary artery calcium scores provide valuable information about the extent of calcium deposits in the coronary arteries, indicating advanced atherosclerosis. However, the usefulness of these scores varies depending on age and other risk factors. In older patients, a positive calcium score may not provide significant additional information, while in younger patients, a positive score suggests a higher risk of future cardiovascular events. A negative calcium score does not guarantee the absence of disease, especially in individuals with high p o b levels. Therefore, while calcium scores can be a useful tool, they should be interpreted in conjunction with other risk factors to make informed treatment decisions.
Importance of Long-Term Perspective on Health
It is crucial to consider long-term health outcomes beyond a specific time horizon, such as 10 years. Thinking about the future and the potential impact on one's career, family, and overall enjoyment of life is essential. By shifting the focus to longer timeframes, individuals can better understand the significance of certain health risks and make more informed decisions. For instance, a 30% chance of developing a health condition in one's lifetime is a meaningful number, whereas a 7.8% risk may be more difficult to comprehend. Understanding the long-term implications helps individuals appreciate the importance of managing higher-risk factors.
The Value of Small Probabilities
Even small probabilities of adverse events can have considerable consequences, and they should not be underestimated. Just as a 5% chance of dying on a commercial plane over the next decade would impact someone's behavior, a 5% risk of developing a health condition should also be taken seriously. It's crucial to consider the potential consequences and the burden of treatment. Comparing different risks and their potential impact on one's life and lifestyle can provide a clearer perspective on the importance of managing risks effectively.
The Role of Uncertainty and Confidence Intervals
The uncertainty associated with risk prediction should be taken into account when making decisions. Confidence intervals provide a range of possible outcomes, indicating the accuracy of a prediction. However, confidence intervals are often not mentioned in guidelines or recommendations. By incorporating a range of viewpoints and considering the uncertainty in the predictions, decision-making processes can become more robust and better reflect the complexity of scientific understanding. It is crucial to acknowledge the limitations of knowledge and to be open to questioning and challenging prevailing consensus.
Allan Sniderman is a highly acclaimed Professor of Cardiology and Medicine at McGill University and a foremost expert in cardiovascular disease (CVD). In this episode, Allan explains the many risk factors used to predict atherosclerosis, including triglycerides, cholesterol, and lipoproteins, and he makes the case for apoB as a superior metric that is currently being underutilized. Allan expresses his frustration with the current scientific climate and its emphasis on consensus and unanimity over encouraging multiple viewpoints, thus holding back the advancement of metrics like apoB for assessing CVD risk, treatment, and prevention strategies. Finally, Allan illuminates his research that led to his 30-year causal model of risk and explains the potentially life-saving advantages of early intervention for the prevention of future disease. We discuss:
Problems with the current 10-year risk assessment of cardiovascular disease (CVD) and the implications for prevention [4:30];
A primer on cholesterol, apoB, and plasma lipoproteins [16:30];
Pathophysiology of CVD and the impact of particle cholesterol concentration vs. number of particles [23:45];
Limitations of standard blood panels [29:00];
Remnant type III hyperlipoproteinemia—high cholesterol, low Apo B, high triglyceride [32:15];
Using apoB to estimate risk of CVD [37:30];
How Mendelian randomization is bolstering the case for ApoB as the superior metric for risk prediction [40:45];
Hypertension and CVD risk [49:15];
Factors influencing the decision to begin preventative intervention for CVD [58:30];
Using the coronary artery calcium (CAC) score as a predictive tool [1:03:15];
The challenge of motivating individuals to take early interventions [1:12:30];
How medical advancement is hindered by the lack of critical thinking once a “consensus” is reached [1:15:15];
PSK9 inhibitors and familial hypercholesterolemia: two examples of complex topics with differing interpretations of the science [1:20:45];
Defining risk and uncertainty in the guidelines [1:26:00];
Making clinical decisions in the face of uncertainty [1:31:00];
How the emphasis on consensus and unanimity has become a crucial weakness for science and medicine [1:35:45];
Factors holding back the advancement of apoB for assessing CVD risk, treatment, and prevention strategies [1:41:45];
Advantages of a 30-year risk assessment and early intervention [1:50:30];
