Statin-Associated Myopathy is the Most Likely Cause
A CK of 526 U/L in a patient on chronic statin therapy with normal BNP is most consistent with statin-associated myopathy rather than cardiac strain from pulmonary hypertension. Cardiac injury from right ventricular strain would be expected to elevate BNP and typically produces much smaller CK elevations, whereas statin myopathy commonly presents with chronic, modest CK elevations in the range you describe 1, 2.
Why This is Statin-Related, Not Cardiac
The normal BNP essentially rules out significant cardiac strain as the cause. Severe pulmonary hypertension causing right ventricular dysfunction sufficient to release CK would invariably elevate BNP 2. The dissociation between elevated CK and normal BNP strongly points away from a cardiac source 2, 3.
CK elevations from cardiac sources are typically much lower than skeletal muscle sources. The cardiac isoform (CK-MB) represents only a small fraction of total CK even in acute myocardial injury, and chronic cardiac strain produces minimal CK elevation 3. A CK of 526 U/L suggests skeletal muscle origin 1.
The chronicity you describe is characteristic of statin myopathy. Statin-associated muscle injury can persist asymptomatically for months to years with modest CK elevations (typically 2-5 times upper limit of normal), which fits your clinical picture 1, 4.
Clinical Context Supporting Statin Etiology
Statin myopathy occurs in 5-10% of patients in clinical practice, making it a common finding. Most cases present as asymptomatic CK elevation or mild myalgias with CK levels in the range of 2-5 times the upper limit of normal 5, 4. Assuming an upper limit of normal around 200 U/L, your patient's CK of 526 U/L represents approximately 2.6 times the upper limit—squarely in the typical range for statin myopathy 1.
All statins carry equivalent risk for myopathy when used at equipotent doses. The ACC/AHA/NHLBI advisory confirms no clinically important differences in myopathy rates among currently available statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, rosuvastatin) 1. This is a class effect, not specific to any particular agent 4, 6.
Management Algorithm for This Patient
Do not discontinue the statin immediately if the patient is asymptomatic. The 2016 ESC/EAS guidelines specify that for CK <4 times ULN without symptoms, you should continue therapy and recheck CK in 4-6 weeks 1. The ACC/AHA advisory similarly states that modest CK elevations without symptoms do not require statin discontinuation 1.
Obtain thyroid-stimulating hormone (TSH) immediately. Hypothyroidism predisposes to myopathy and exacerbates statin-related muscle injury, making it a critical reversible factor to identify 1, 2, 3. This should be checked in any patient with elevated CK on statins, regardless of symptoms 2.
Monitor for symptoms and serial CK levels. Instruct the patient to report any muscle pain, tenderness, weakness, or dark urine immediately 1, 7. Recheck CK in 4-6 weeks; if rising or if symptoms develop, discontinue the statin 1, 3.
Critical Thresholds Requiring Action
Discontinue the statin immediately if CK rises above 10 times the upper limit of normal (approximately >2000 U/L) or if muscle symptoms develop. This threshold indicates significant myopathy risk and potential progression to rhabdomyolysis 1, 7. Check renal function and monitor CK every 2 weeks until normalization 1.
For CK between 4-10 times ULN with symptoms, stop the statin and monitor weekly. Once CK normalizes and symptoms resolve (typically 2-6 weeks), consider rechallenge with a lower dose of the same statin or switch to an alternative agent 1, 3, 5.
Common Pitfalls to Avoid
Do not assume cardiac origin without elevated BNP or troponin. The combination of elevated CK with normal BNP makes cardiac strain extremely unlikely 2, 3.
Do not ignore asymptomatic CK elevations entirely. While routine CK monitoring in asymptomatic patients is not recommended, once an elevation is discovered, it requires follow-up to ensure it doesn't progress 1, 3.
Do not attribute all CK elevations to statins without excluding other causes. Check TSH, review for other myopathic medications, assess for recent strenuous exercise, and consider other muscle diseases if CK continues rising despite statin discontinuation 1, 2, 3.
Rare but Important Consideration
If CK elevation and weakness persist after statin discontinuation, consider statin-associated autoimmune myopathy (anti-HMGCR antibody-positive). This immune-mediated necrotizing myopathy occurs in rare cases, presents with proximal weakness and very high CK (mean ~6800 U/L), and requires immunosuppressive therapy rather than simple statin discontinuation 1, 2, 8. This entity would be characterized by failure of CK to normalize within 6-8 weeks after stopping the statin 8.