The Power of Low Lifelong LDL-C

A high-impact genetic association study found that people with certain genetic variants were 50% less likely to develop coronary heart disease. The findings reveal the importance of maintaining low LDL-C (or “bad” cholesterol) levels over a lifetime.

Pharmacological LDL-C management may reduce the risk of developing CHD by 22%, but this study found that people who had variations in either APOB or PCSK9 (two genes known to be associated with LDL-C) were even more protected against CHD. 

The authors combined genetic and clinical data from more than 200,000 participants from 5 NHLBI prospective cohorts and the UK Biobank. Of these, 139 (0.7%) carried a truncating mutation in either APOB or PCSK9–switching these genes off. 

Over a median of 21.5 years…

  • A CHD event (like a heart attack or death) was far less likely in APOB or PCSK9 variation carriers than noncarriers (8.6% vs. 16%), corresponding to a 49% reduced CHD risk (HR: 0.51). 
  • Carriers had a 45 to 49 mg/dL lower average untreated LDL-C level. 

To put the magnitude of the 49% reduced CHD risk into perspective, here is how traditional risk factors affected the likelihood of developing CHD. 

  • No diabetes reduced risk by 53%
  • No hypertension reduced risk by 25%
  • Not smoking reduced risk by 43%. 

That’s right: a APOB or PCSK9 variation carrier who smokes is more protected against CHD than a noncarrier who does not smoke. 

The Takeaway
Analysis of DNA variants that turn off APOB or PCSK9 revealed the power of lifelong low LDL-C. For LDL, it’s not only about how low the levels are, but for how long those levels have stayed low.

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