Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What is LDL cholesterol? What blood level of LDL cholesterol is considered optimal and why are high levels of LDL cholesterol a key marker of death risk from heart disease?
Cholesterol is a lipid that is both produced in the liver and gained through food intake. Some amount of cholesterol, which is transported through the bloodstream in lipoproteins, is essential for normal body function.
There are different types of lipids or fats, including low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.
While HDL (“good”) cholesterol is carried from parts of the body to the liver, which removes the cholesterol from the body, high levels of LDL (“bad”) cholesterol remain in the bloodstream and can cause arterial clogging, increasing the risk of stroke and heart disease.
Blood lipid levels are the primary biomarkers for cardiovascular disease, which accounts for one in every three deaths in America.
Every 10 mg/dL decline in LDL cholesterol is associated with an approximately 5-13% decline in major vascular disease events, such as strokes and mortality.
LDL cholesterol levels of 100 mg/dL or lower are considered optimal by the American Heart Association, while LDL cholesterol levels of 100-129 mg/dL are considered near or above optimal, 130 to 159 mg/dL is borderline high, 160 to 189 mg/dL is high, and 190 mg/dL is considered very high.
To support heart health, it is very important to maintain the optimal LDL cholesterol levels. Treatments typically include lifestyle modification and may include therapy with lipid-lowering medications such as statins.
How have LDL cholesterol blood levels changed over the past several decades?
Average blood cholesterol values, the primary cardiovascular disease biomarker, have declined in the United States since at least 1960.
Results of three National Health and Nutrition Examination Surveys (NHANES) of nearly 40,000 patients for the years 1988 to 2010 demonstrated that LDL cholesterol levels have declined in the United States while the use of lipid-lowering medications has increased.
These trends are also reflected in the mortality rates attributable to cardiovascular disease, which declined by approximately 60% from 1970 through 2000, and by 30% from 2000 through 2009.
These improvements are due largely to increased use of evidence-based medical therapies, such as statins, which lower lipid levels, as well as lifestyle changes, such as diet and exercise.
Based on these factors, the American Heart Association (AHA) 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health for all Americans. But as the latest Quest Diagnostics Health Trends’ study suggests, improvements in cholesterol levels may have stalled.
When did it come to your attention that the declines in LDL cholesterol blood levels had come to an end?
We were not aware of this pattern until we produced our latest Quest Diagnostics Health Trends study. These are studies based on analysis of the company’s diagnostic data.
Our study is the first nationally-representative analysis to show that improvements in the United States in LDL cholesterol blood levels, a key marker of death risk from heart disease, abruptly ended in 2008, and may have stalled since.
Specifically, we found a 13% decline in the annual mean LDL cholesterol level of the study population over the 11-year period, similar to the NHANES data. However, we also found the decline ended in 2008, and stalled between 2009 and 2011, the last year we studied.
The peer-reviewed, open access journal PLOS ONE published the study in May 2013.
What sparked researchers at Quest Diagnostics to investigate this sudden end to LDL cholesterol blood level declines?
A team of researchers at Quest Diagnostics was inspired to perform the study after NHANES published its data showing declining blood cholesterol values from 1999 through 2010.
As we began our analysis, we had no pre-existing theories regarding trends in LDL cholesterol levels; in fact, we assumed we might find a continuation of the same trends that had occurred over the last fifty years. The finding that LDL cholesterol levels have plateaued since 2008 is novel.
What did the study involve?
Our study examined de-identified low-density lipoprotein blood-serum cholesterol test results of nearly 105 million individual adult patients of Quest Diagnostics of both genders in all 50 states and the District of Columbia from 2001-2011.
The study is the largest of LDL cholesterol levels in an American population, and the first large-scale analysis to include data from recent years 2009-2011.
Other studies that have examined population trends in LDL cholesterol have been constrained by smaller populations, shorter study periods, and smaller geographical coverage.
Our study reported data annually whereas most recently published studies, such as the NHANES research, report results in time periods that cover multiple years, which may mask the plateau observed in our study.
In addition to finding that LDL levels stalled, did your study provide any other notable insights?
Yes, we found differences between men and women. Specifically, we found a slightly greater decline in LDL cholesterol levels among men compared to women.
These differences may reflect meaningful differences in the prescription rate and effectiveness of lipid-lowering interventions, including statins and lifestyles, between genders.
The differences may also be due in part to under-appreciation of heart disease risk in women. Medical understanding of differences in heart disease risks by gender is relatively new.
For instance, female-specific American Heart Association guidelines for women were introduced only in 1999. More investigation is needed to understand the reasons for the gender differences.
What hypotheses were put forward as the reasons behind this trend?
It’s reasonable to hypothesize that the economic recession, which began at about the same time that LDL cholesterol values flattened in our study, possibly played a role in the plateau of LDL cholesterol levels.
Patients dealing with financial constraints may have been less inclined to visit their physician or use their medications at full dose, limiting access to and effectiveness of treatment.
Individuals may also have experienced changes in stress levels, diet, sleep and other behaviors, due to the poor economy, which in turn may have adversely impacted lipids.
It’s also possible that statins users in the study may have reached the maximum therapeutic-threshold level or that increases in obesity prevalence or other co-morbid factors during the 11 years of the study period contributed to the LDL cholesterol plateau.
Analysis of these theories falls outside the purview of our study, but we believe they warrant additional investigation.
What can be done to reverse this trend?
We hope this new study will encourage additional population research to inform public health efforts. But we also believe the study should prompt individual patients to be vigilant about practicing healthy behaviors and lipid-lowering treatment plans.
The most important lesson to be gleaned from our study is that patients need to remain engaged in their health care and to communicate with their physicians.
Given the high mortality rate from cardiovascular disease, this is especially important with heart health. If economic or other factors will potentially affect the ability of patients to maintain a consistent treatment regimen, they should talk freely, honestly and without embarrassment to their clinician regarding all possible options.
Our hope is physicians and patients will have more productive conversations about the importance of LDL control to cardiovascular health as a result of this study.
What are Quest Diagnostics’ plans for the future?
Quest Diagnostics is focused on developing and offering diagnostic innovations along a continuum of care. We are particularly interested in diagnostics that can help prevent or arrest disease – that is, diagnostic services that can help identify risk factors for disease, thereby potentially helping physicians to prevent its onset, or disease in early treatable stages.
Certainly, this Quest Diagnostics Health Trends study speaks to the need for the medical community and patients to be vigilant in taking steps to identify heart health risks before disease occurs. The prevention of disease is always the optimal outcome.
Where can readers find more information?
Please visit our website at www.QuestDiagnostics.com or access the study at www.QuestDiagnostics.com/HealthTrends
About Dr. Harvey Kaufman
Harvey W. Kaufman, M.D., is Senior Medical Director for Quest Diagnostics and the company’s Medical Director for its General Health and Wellness business.
He is also the principal medical investigator for Quest Diagnostics Health Trends studies, and has served in a variety of roles for the company for more than 20 years.
Dr. Kaufman graduated from Massachusetts Institute of Technology (S.B. and S.M.), Boston University School of Medicine (M.D.), and New York University's Leonard N. Stern School of Business (M.B.A. with Distinction).
Dr. Kaufman is board certified in Anatomic and Clinical Pathology and Chemical Pathology. He serves on various national and local organizations, including the Quest Diagnostics Foundation.