Cardiovascular disease remains the leading cause of death worldwide resulting in 16% of death annually. Coronary artery disease accounts for over 600,000 deaths annually and is the leading cause of mortality in the US.
Modifiable risk factors that include a healthy lifestyle (diet, exercise, and smoking cessation), dyslipidemia, hyperglycemia, and hypertension can prevent 4 out of 5 coronary events and 80% of medical expenditure. LDL-C is the primary target to reduce coronary events in dyslipidemic patients.
Clinical trials of LDL-C lowering therapies had demonstrated a dose-dependent linear association between the magnitude of exposure to LDL particles and an increased risk of cardiovascular disease. Over the last four decades, multiple clinical studies have demonstrated a decreased risk of cardiovascular morbidity and mortality in patients on statin therapy. The yearly event rate observed is strongly associated with the absolute LDL-C level achieved.
OVERALL ADULT POPULATION: WHO SHOULD BE TREATED WITH STATIN?
In the overall adult population of 40-75 yrs, the calculation of the atherosclerotic cardiovascular disease (ASCVD) risk allows the identification of patients at sufficient risk to merit treatment with a high likelihood of net benefit. The 10-yr risk can be calculated using the pooled equation. In adults with borderline and intermediate risk (5 to <20% 10-yr risk) it is reasonable to use additional risk-enhancing factors to guide decisions about starting statin treatment. Among those is a family history of premature ASCVD ( women <60 yrs. and men <50 yrs.), South Asian ancestry, chronic inflammatory disease (Rheumatoid arthritis, Lupus, long COVID), early menopause, eclampsia and preeclampsia, metabolic syndrome, and chronic kidney disease).
In patients with cholesterol between 70 and 189 mg/dL, it is recommended to start with a healthy lifestyle that includes exercise and eating a diet rich in fruits and vegetables as well as a Mediterranean diet. When elevated cholesterol persists, a low to medium-intensity statin is recommended.
The data on a statin for primary prevention is quite compelling. The US Preventive Services Task Force (USPSTF) recently reviewed 22 trials of moderate-statin intensity in patients 40-75 years of age and no coronary disease or symptoms of ASCVD and moderate risk (7.5-20% 10 yr-risk). In the pooled analysis, statin decreased all-cause mortality by 8%, fatal or non-fatal stroke by 22%, and fatal or non-fatal myocardial infarction (MI) by 33%. In the landmark, WOSCOPS study of pravastatin 40 mg, cardiovascular mortality, and non-fatal MI was reduced by 31% at 6 yrs. Twenty years later, a reduced total burden of disease is evident with a reduction in cardiac admissions for coronary interventions by 18%, MI by 24%, and heart failure by 35%. For these reasons, the majority of countries are much more likely to use a statin.
The magnitude of statin benefit is proportional to a person’s ASCVD risk: a patient with borderline 10-yr risk of 5-7.5% will have a smaller benefit compared to a patient with an intermediate risk of >10%, but both groups benefit. Several mechanisms are involved and include atherosclerotic plaque stabilization, decrease inflammation of the coronary arteries, and regression of atherosclerosis reducing new plaque formation and reduction of narrowing in the arteries.
ADULTS WITH FAMILIAL HYPERCHOLESTEROLEMIA (FH) SHOULD BE TREATED WITH A STATIN.
FH is characterized by lifelong exposure to very high levels of LDL cholesterol resulting in an increased risk of premature ASCVD and death. If left untreated, it increases the risk of early CAD by 20-fold. It accelerates ASCVD by 20-30 yrs in women and 10-20 yrs in men. In other words, women at 30 years of age have the same risk of CAD as if they were 60 years old.
FH can be diagnosed when LDL-C >190 mg/dL in combination with premature ASCVD or similar LDL-C in a first-degree relative.
Early initiation of therapy does lower the risk significantly. High-intensity statin constitutes the first-line treatment for patients with FH and has been demonstrated to lower the risk of cardiovascular death and all-cause mortality. Atorvastatin 80 mg or rosuvastatin 40 mg can provide a modest reduction in LDL-C (10-25%). The addition of ezetimibe can add an additional 10-15% reduction in LDL when combined with a healthy lifestyle. Monoclonal antibodies to PCSK9 have produced an average of 20-30% reduction in LDL-C when added to statin. Inclisiran, a small interfering RNA molecule acts at the level of the liver cell and reduces the production of PCSK9 through gene silencing. It is being studied in patients with FH.
ADULTS WITH DIABETES MELLITUS AND HYPERCHOLESTEROLEMIA SHOULD BE TREATED WITH A STATIN.
Type 2 diabetes or adult-onset diabetes is a chronic disease characterized by high levels of blood sugar, usually 126 mg/dL or A1C >6.5. This is the result of the body becoming resistant to insulin and cannot use insulin properly.
The prevalence of diabetes mellitus continues to grow and coronary artery disease constitutes the major cause of morbidity and mortality in diabetic patients. Previous case-control studies have found that, compared to non-diabetics, diabetic subjects have more severe coronary artery disease, more extensive coronary calcifications, a higher prevalence of left main coronary lesions (widowmaker lesion), and fewer coronary collaterals. The overall mortality is 4 to 5 times higher for women and twice as high in men with diabetes when compared to non-diabetics.
Several studies have demonstrated that moderate-intensity statin can reduce coronary events and stroke but there remain significant residual risks (8.5% in a little over 3 yrs). When multiple risk factors are present (hypertension, smoking combined with hyperlipidemia), a high-intensity statin is recommended with the goal of reducing the LDL-C by 50% or more.