Framingham Heart Study shows that HDL Cholesterol Levels should not be interpreted in a vacuum!

High-density lipoprotein (HDL cholesterol) has long been nicknamed the ‘good cholesterol.’ It is well-known that high blood levels of HDL are associated with a decreased risk from cardiovascular disease (CVD). Recently, researchers have been trying to determine whether or not HDL by itself is a strong independent predictor of CVD. In other words, how well do HDL levels predict CVD risk when other factors such as blood triglycerides and LDL (the bad cholesterol) are considered?

To try to answer this important question, 3590 men and women enrolled in the Framingham Heart Study were examined between 1987 and 1991. During this baseline exam, blood levels of total cholesterol, HDL, LDL, and triglycerides were measured after an overnight fast. These four components comprise what is known as a blood lipid profile. In addition age, sex, body mass index (BMI), smoking status, hypertension, and diabetes mellitus were also carefully taken into consideration.

‍Participants were then divided into eight groups based on their blood HDL, triglyceride, and LDL values:‍Group 1:Isolated low HDL. This was defined as having an HDL value <40 mg/dL in men or <50 mg/dL in women, with optimal levels of both LDL and triglycerides (<100 mg/dL for each).Group 2:Low HDL with optimal triglycerides and elevated LDL (>100 mg/dL)Group 3:Low HDL with elevated triglycerides (>100 mg/dL) and optimal LDLGroup 4:Low HDL with elevated levels of both triglycerides and LDL (>100 mg/dL)Group 5:High HDL (>40 mg/dL in men or >50 mg/dL in women) with optimal levels of both triglycerides and LDLGroup 6:High HDL with optimal triglycerides and elevated LDLGroup 7:High HDL with elevated triglycerides and optimal LDLGroup 8:High HDL with elevated levels of both triglycerides and LDL (>100 mg/dL)Participants were followed through 2011. During the follow-up period, the researchers were primarily interested in fatal or nonfatal cardiovascular events (heart attack and stroke). In the Figure below, the risk of these events in the eight groups is shown.

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In the Figure, we are using Group 1 (low HDL, optimal triglycerides, and optimal LDL) as the reference group. The novel finding in this study was that among participants with low HDL, the risk of CVD was significantly greater when elevated triglycerides (30% higher risk), elevated LDL (30% higher risk), or elevations in both (60% higher risk) were present.This finding tells us that CVD risk in people with low HDL varies considerably, depending on their blood triglyceride and LDL values. On the other hand, individuals with high levels of HDL clearly had a significantly decreased risk of CVD events, particularly when both triglyceride and LDL levels were optimal (40% lower risk), or when just one or the other was elevated (30% lower risk). Individuals with high HDL who also had elevated triglycerides and LDL did not see much of a benefit, with a non-statistically significant 10% reduction in risk when compared to the reference group.This study tells us a couple of important things. First, HDL levels are still a key factor in determining CVD risk, but these levels must be considered along with blood triglyceride and LDL levels. Secondly, when optimal levels of triglycerides and LDL are present, CVD risk is considerably lower when HDL levels are high rather than low. Finally, having high rather than low HDL is protective when either triglyceride or LDL levels are high. It is often said that the seeds of cardiovascular disease are planted during the childhood and adolescent years. Therefore, the American Heart Association and other world-renowned groups recommend a baseline blood lipid profile for everyone at age 20. This should be done at a younger age if a strong family history of CVD is present!

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‍ReferenceBartlett, J., Predazzi, I., Williams, S., Bush, W., Kim, Y., Havas, S.,...Miller, M.  Is isolated low high-density lipoprotein cholesterol a cardiovascular disease risk factor? New insights from the Framingham offspring study. (2016). Circ Cardiovasc Qual Outcomes, 9:206-212. DOI: 10.1161/CIRCOUTCOMES.115.002436