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Does Lifelong Low LDL-Cholesterol (Genetic) Reduce Heart Risk? YES!

By February 4, 2023Kahn Longevity Center
LDL cholesterol control
Importance  There are genetic variants that are inherited at birth and are associated with significantly lower low-density lipoprotein cholesterol (LDL-C) concentrations for life. These genetic “experiments” permit asking the question whether a lifelong lower LDL-C lowers the risks of coronary heart disease (CHD) like heart attacks. I published data like this in 2012 and showed with my co-authors that there was a large reduction in the risk of CHD in those born with genetic variants leading to a lifelong low LDL-C. A new study using a large, multiracial prospective population adds to this data.

STUDY: This studied included participants from 5 National Heart, Lung, and Blood Institute (NHLBI) studies and the UK Biobank. NHLBI study participants aged 5 to 84 years were recruited between 1971 and 2002 across the US and underwent whole-genome sequencing. UK Biobank participants aged 40 to 69 years were recruited between 2006 and 2010 in the UK and underwent whole-exome sequencing. Data were analyzed from June 2021 to October 2022.

RESULTS  Among 19 073 NHLBI participants in the USA, only 139 (0.7%) carried the genetic variation that was associated with 49 mg/dL lower LDL-C. Over a follow-up of 21.5 years, incident CHD was observed in 8.6% vs  16.0% of the “non-inherited” group, or a 50% favorable reduction in CHD.

Among 190 464 UK Biobank participants, 0.4% carried a favorable genetic pattern associated with 45 mg/dL lower LDL-C. Estimated CHD risk by age 75 years was 3.7% vs 7.0% in noncarriers, corresponding to a 50 % reduction in CHD.


Among 209 537 individuals in this study, 0.4% carried a favorable genetic variaton that was associated with less exposure to LDL-C over there whole life. There was a 49% lower risk of CHD. This supports the Cholesterol Hypothesis that lowering LDL-C throughout life using lifestyle, and if needed, supplements and medication, favor the avoidance of heart disease and heart events like heart attacks.


Dr. Joel Kahn