Attia Statins

However, like all lipids (fats), cholesterol is insoluble in water-based plasma and needs a hydrophilic peptide (a so-called apoprotein) to enwrap and transport the lipids in particles called lipoproteins. Though various classes of lipoproteins exist, only those containing apoB, short for apolipoprotein B, can enter, aggregate, and be oxidized within an arterial wall, which in turn promotes an inflammatory response, the development of plaques, and thus, ASCVD.

Low-density lipoproteins (LDLs), each of which has a single apoB molecule, make up 90-95% of all apoB-containing lipoprotein particles due to their prolonged plasma residence time relative to other apoB particles, and therefore, LDL cholesterol (LDL-C) is frequently used to estimate apoB.

How do statins help?

LDL-C concentration of <100 mg/dL is considered “optimal”

Statins reduce the amount of circulating apoB through the inhibition of hepatic (liver) cholesterol synthesis

Seven statin medications currently have approval from the Food and Drug Administration for LDL reduction: 
  atorvastatin
  fluvastatin
  lovastatin
  pitavastatin
  pravastatin
  rosuvastatin
  simvastatin.



An individual who achieves an LDL-C of 75 mg/dL after decades of creeping up to a peak of 160 mg/dL is still at far greater ASCVD risk than an individual who has always been at 75 mg/dL. Why? Because the progression of ASCVD is a function of both apoB concentration and duration of exposure.

It's like smoking

SIDE EFFECTS

Like any medication, statins are not completely without possible adverse effects, including gastrointestinal distress, brain fog, and dose-related muscle pain. The most common side effect, muscle pain, has a variety of causes, and in a meta-analysis of randomized controlled trials, there was around a 7% relative increase in this symptom between the control and intervention groups during the first year, corresponding to an absolute additional rate of muscle pain or weakness of 11 events per 1000 person-years. After the first year, the statin groups showed no increase in muscle-related symptoms compared to the control groups. More potent statins, such as atorvastatin or rosuvastatin, had slightly higher rates compared to more moderate or less potent statins. Depending on the severity of symptoms, switching to a nonstatin therapy, a statin with lower rates of adverse effects, or a lower dose statin (with a combination of other LDL-lowering medications) may be an option. Several alternative therapeutic options to statins – such as PCSK-9 inhibitors or bempedoic acid – are also effective in combatting high LDL.

Other more serious side effects include rhabdomyolysis, elevated liver enzymes, and the development of type 2 diabetes. Rhabdomyolysis is a severe condition that causes skeletal muscle breakdown, and in such cases, statin use should be discontinued.  Less than 0.05% of patients on statins develop rhabdomyolysis, but concurrent use of certain antibiotics or other drugs such as fibrates increases this risk. Statin therapy is associated with elevated hepatic transaminases in anywhere from 1-3% of patients. Most of these cases are asymptomatic and do not require discontinuation of therapy; however, statin use in patients with acute liver disease is contraindicated for this reason.

Elevated blood glucose is another possible side effect of statin use, and the onset or progression of type 2 diabetes is another reported effect of statins. The exact mechanism for this development is not currently known, but there are several pathways of glucose metabolism that may be affected. The excess risk of new-onset type 2 diabetes from any statin is estimated to be 9-12% higher when compared to placebo, and in large meta-analyses, this outcome is a moderate effect. However, the risk of new-onset diabetes is statin-specific: atorvastatin, rosuvastatin, and simvastatin have reported dose-dependent excess risks from 10% to upwards of 40% depending on the study. Some of the variability between risks reported is due to heterogeneity in statin dose and duration of treatment, as well as the population itself – one of the strongest risk factors for a new diagnosis was metabolic syndrome or pre-diabetes at baseline. In other words, those most likely to be pushed over the edge already had some degree of metabolic dysfunction.