🌋Statins: WTF (Why The Fascination)?
Statins; Why, What, How
🩺 Understanding Statins and Cholesterol Management
✅ Benefits of Statins
Statins offer two primary benefits aimed at enhancing longevity and quality of life (help us towards our goal of dying less soon and less miserably):
📉 Lower Cholesterol Levels: Primarily aimed at reducing LDL cholesterol.
🔬 Pleiotropic Effects: which involve benefits beyond cholesterol reduction.
💡 LDL and HDL Cholesterol
👎 LDL ("Lousy") Cholesterol: The "bad" cholesterol you want low.
👍 HDL ("Happy") Cholesterol: The "good" cholesterol you want high. Statins' effects here are minimal or variable—sometimes increasing slightly, minimally decreasing, or remaining unchanged.
Lowering cholesterol with statins primarily aims to reduce LDL (Low-Density Lipoprotein) cholesterol, which can be remembered as "L for Lousy", and is the stuff you want low. Statins' effects on HDL (High-Density Lipoprotein) cholesterol, "H for Happy", the stuff you want high, are minimal or variable; statins may slightly increase HDL, minimally decrease it, or leave it largely unchanged.
🛡️ Beyond Numbers: Plaque Stabilization
Statins also significantly lower heart attack and stroke risks through:
🔒 Stabilizing Existing Plaques: Strengthens plaque structure.
🔥 Reducing Arterial Inflammation: Minimizes inflammation within arteries.
While improving lab numbers for LDL cholesterol is crucial for reducing future plaque build-up, statins also significantly reduce the risk of heart attacks and strokes through additional benefits known as pleiotropic effects. These include stabilizing existing plaques and reducing inflammation within arteries. Although medications like 💉 PCSK9 inhibitors have shown to offer additional benefits beyond LDL reduction, current evidence does not support their role in plaque stabilization as strongly as statins.
⚠️ Plaque Inflammation and Rupture
Cholesterol build-ups, or plaques, within arteries can cause inflammation. Sometimes these plaques can crack or rupture, prompting the body to respond as it would to any injury: by forming a clot. However, clot formation inside an artery can block blood flow, resulting in a heart attack or stroke, depending on the location and severity of the clotting event.
Statins reduce inflammation and stabilize plaques, making them less likely to rupture.
🔎 Types of Plaque
Plaques vary significantly in severity:
🦴 Calcified Plaques: Visible on scans due to calcium deposits.
☁️ Soft Plaques: Invisible on imaging, yet are likely more prone to rupture.
Plaque presence ranges widely in size and severity; from insignificant (a few molecules briefly holding hands as they pass by) to severe blockages (akin to a hippopotamus stuck in your bathroom doorway).
Calcified plaques are older cholesterol deposits that have absorbed calcium over time, making them visible on imaging scans due to their ability to block x-rays, similar to bones. These look to be a stronger predictor of heart attack risk.
Soft plaques are early-stage deposits without calcium, making them invisible on standard imaging scans. Despite their invisibility, soft plaques are more prone to rupture, though there is some debate on if they really are more vulnerable.
🌟 Unique Advantage of Statins
the caps over plaques and reduce inflammation, rupture risk. Other medications
Statins uniquely strengthen and help toughen the fibrous caps over cholesterol deposits and limit or reduce inflammation, markedly lowering the likelihood of rupture. Other cholesterol-lowering medications primarily improve cholesterol numbers without strongly influencing plaque stability and therefore have a less robust link to directly lowering the risk of heart attacks and strokes.
🔬 Emerging Treatments: Small Molecules
Innovative treatments, recent and still under investigation, include:
💉 PCSK9 inhibitors: Injectable therapy significantly reducing LDL by targeting PCSK9.
💊 Bempedoic Acid: Oral medication working upstream of statins, approved as adjunct therapy.
LP(a): Lipoprotein (a) or “big L little a”, is a particle that carries cholesterol in the blood and is a risk factor for cardiovascular disease.
Research continues to investigate new small molecule treatments that lower cholesterol and potentially offer additional heart benefits:
Inclisiran, an injectable small interfering RNA (siRNA) therapy, significantly reduces LDL by targeting PCSK9 production. Its role in plaque stabilization continues to be evaluated.
Bempedoic Acid, a newer oral medication, acts upstream of statins in cholesterol synthesis and is approved as an adjunct therapy. Ongoing studies are evaluating its potential cardiovascular benefits, including possible effects on plaque stability.
Lipoprotein (a): Lp(a), or LP little a, is a particle that carries cholesterol in the blood and is a risk factor for cardiovascular disease. There is not currently a specific treatment or medication that lowers Lp(a) but research is in progress on several fronts, looking into niacin (vitamin B3), which can provide reductions in LP(a) though studies have failed to show it reduces heart disease risk, and new medications like short interfering RNA (siRNA) that disrupt formation of Lp(a).
📌 Recommendations
For most patients, continued use of statins is strongly recommended due to their proven benefits in reducing LDL cholesterol and stabilizing plaque. For personalized discussions on risks, benefits, or additional therapies, consult your healthcare provider.
Old Habits Die Hard
There is a long and entrenched history of thinking patients need to be fasting for lipid checks, but we can do either.
Total, HDL, and LDL levels change over a longer timeframe, so fasting is not really needed, however w/ high triglycerides, fasting is still preferred since recent meals can dramatically raise those levels.
Lipids: Testing
Some organizations have adopted a non-fasting lipid panel as the standard, or at least have made it an option, for patients who are unable to fast for the traditional 12 hours.
Reference this article; lipids do not substantially shift after eating, they change over a longer period.
Triglycerides and glucose are more responsive to recent intake and will change over a shorter timeframe.
Fasting for tests cardiology would run is as follows:
Fasting glucose; Recommended: 12 hour fast
Hx of high Triglycerides; Recommended: 12 hour fast along with a 24 hour fast from alcohol.
🧠💊 Statins: Cognitive Concerns and Diabetes Risk
This all boils down to:
The memory concern is unproven but we do have good evidence of the cardiac benefits and feel those outweigh the question of conative risk
There is a statistically valid (though small) increased risk of diabetes associated with long-term statin use.
🤔 Cognitive Concerns: What's Known and Unknown
The way it stands is that there are two open questions on opposite sides of this:
There are observations suggesting statins may produce cognitive impairment.
Some studies suggested they may have a role in the prevention of dementia.
Concerns have arisen regarding statins' potential effects on cognition and memory. Currently, the evidence around this issue remains mixed and inconclusive. While memory-related concerns are unproven, the well-documented cardiovascular benefits of statins generally outweigh these potential cognitive risks.
⚠️ Possible Cognitive Impairment
Some observational reports suggest statins might contribute to short-term memory issues or cognitive impairment. Drug manufacturers even list cognitive impairment as a potential side effect. However, rigorous scientific studies have not consistently supported this concern.
🧩 Potential Dementia Prevention
Interestingly, some research indicates statins might reduce the risk of dementia, including Alzheimer's disease. These findings are preliminary and have not yet established a clear preventive benefit.
🔍 Clarifying Cognitive Impairment vs Dementia
It is also not clear that the cognitive impairment is in the same vein as Alzheimer's. They both certainly can impact memory but may be very different processes impacting the brain in different ways. This remains an active research area.
It is crucial to distinguish between:
🌀 Cognitive Impairment: Typically reversible issues with memory or mental clarity, potentially medication-related.
🧠 Dementia (including Alzheimer's): Progressive and long-term cognitive decline, usually irreversible and associated with different biological processes.
❤️⚖️ Balancing Cardiac Benefits vs Cognitive Concerns
Cardiology specialists emphasize that the well-established cardiovascular benefits of statins, such as significantly reducing heart attack and stroke risk, outweigh the currently uncertain and unproven risks related to cognitive impairment.
An interventional cardiologist summarized this clearly:
Cognitive impairment is a possible but unproven side effect.
Proven cardiovascular protective benefits greatly outweigh uncertain cognitive risks.
📈 Diabetes Risk: A Valid Consideration
Unlike cognitive concerns, the increased risk of diabetes associated with long-term statin use is supported by research. However, this risk, though statistically valid, is relatively small compared to the substantial cardiovascular benefits provided by statins.
👥 Patient-Centered Decision Making
Decisions regarding statin use should consider each patient's unique situation, including:
📌 Individual cardiovascular risk
📌 Family history of dementia or diabetes
📌 Personal health concerns and lifestyle factors
📌 Medication tolerance
Patients are encouraged to discuss their specific concerns with their healthcare provider to make well-informed decisions about statin therapy, however, the implications on either side of these considerations fall on the patient and their unique situation, body, and life, not their healthcare provider, so the patient ultimately has to decide for themselves if they want to take a statin.
