Illustration of red blood cells moving through clogged artery to indicate cholesterol build up as a result of homozygous familial hypercholesterolemia
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An analysis of more than 460 million lipid test results from 17 countries on five continents has provided evidence that variation in cardiovascular disease risk is based on influences from where a person lives and their sex. The study, performed by researchers at Johns Hopkins University and the Quest Diagnostics-led Global Diagnostics Network (GDN) is believed to be the largest study ever to understand the variability of lipid levels in patients worldwide.

According to the results, variability in the lipid-associated risk of cardiovascular disease  could be attributed in part to differences in genetics, lipid testing, lifestyle habits, pharmacologic treatments. The research, published in the European Heart Journal, found that in five of the 17 countries, people tested exhibited suboptimal total cholesterol levels compared with the World Health Organization’s (WHO) target. The research also showed that dangerous levels of cholesterol were at their highest during middle age in both sexes in most countries, though the cholesterol of males peaked 10 years earlier than in females.

“With nearly half a billion lipid results, this analysis included a huge scale of recent data that was examined across the globe to inform public health,” said lead author Seth S. Martin, MD, professor of medicine at Johns Hopkins University School of Medicine. “As these results inform the conversation that patients and clinicians have when selecting therapy, the distributions observed in our study might be useful to laboratories in refining interpretative ranges and alert values.”

The analysis included medically recognized markers of cardiovascular disease including total cholesterol level, levels of high-density lipoproteins (HDL), low-density lipoprotein (LDL), and triglyceride. While the WHO clinical practice guideline recognizes the clinical value of lipid testing, scant research has been conducted on a global scale to identify geographical differences and how these could help drive public policy in high-risk populations.

Key findings of the analysis that used lipid testing conducted between 2018 and 2020 include:

  • Highest total cholesterol levels in two European countries: Seven countries evaluated had mean total cholesterol levels exceeding the WHO-defined risk threshold of 5.00 mmol/L (193 mg/dL): Japan, Australia, North Macedonia, Switzerland, Germany, Slovakia, and Austria. Of these, the highest mean total cholesterol levels were in Austria (5.40 mmol/L, 208.8 mg/dL) and Germany (5.35 mmol/L, 206.9 mg/dL).
  • Countries with lowest cholesterol levels spanned the Americas, Middle East and Asia: The countries with the lowest mean total cholesterol levels were the Republic of Korea (4.58 mmol/L, 177.1 mg/dL), Turkey (4.74 mmol/L, 183.3 mg/dL), and the United States (4.75 mmol/L, 183.6 mg/dL).
  • The Americas region showed strikingly similar patterns, with age group-based patterns of total cholesterol in females and males remarkably similar among three countries in the Western Hemisphere (Brazil, Canada, and the United States).
  • Differences by sex held steady in most countries, with total cholesterol and LDL cholesterol levels peaking in males between ages 40-49 years and females peaking at ages 50-59 years. Yet, a higher proportion of females than males had rates of LDL cholesterol levels at or above 4.91 mmol/L, a level the WHO considers highly elevated, in all but four countries (Brazil, Saudi Arabia, Spain and United Arab Emirates). In every country except India, total cholesterol levels among females were highest in the 50–59-year age group.

Variation from country to country may be the result of “cultural dietary and physical activity patterns,” the study’s author speculated, and may also include varying economic conditions and access to lipid testing. Difference may also reflect genetic differences between populations the influence of genetics on the development of conditions such as familial hypercholesterolemia.

“The GDN study is important for demonstrating what has long been suspected: that cardiovascular disease is an urgent public health problem in multiple countries, not just the U.S.A., and cultural and genetic factors likely contribute to development of this largely preventable disease,” said co-author Harvey W. Kaufman, MD, senior medical director, Quest Diagnostics. “We hope our study ignites greater focus of public health resources on the global problem of cardiometabolic disorders.”

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