By Deborah Borfitz
January 4, 2021 | Researchers in China have developed a noninvasive skin cholesterol detection system that could be useful in the long-term lipid management of cardiovascular diseases, meeting a critical unmet need. The traditional indicator, low-density lipoprotein cholesterol (LDL-C), is prone to false positives, and lipid levels measured by routine blood cholesterol tests fluctuate based on diet, exercise, and weight, according to Yikun Wang, a researcher engaged in the research, development, and industrialization of medical spectral imaging at the Anhui Institute of Optics and Fine Mechanics within the Chinese Academy of Sciences’ Hefei Institutes of Physical Science.
To get a rapid read on their cholesterol, patients have only to put their hand on the desktop-sized unit. Cholesterol content in the skin varies less in a short period of time and is also closely associated with atherosclerotic cardiovascular diseases, he notes.
The invention examines changes in levels of apolipoprotein B, the main protein in LDL cholesterol. When put to the test in a study that recently published in Lipids in Health and Disease (DOI: 10.1186/s12944-021-01571-0), the approach gave patients with low initial LDL-C more informative data on lipid management than traditional LDL-C readings. It also showed potential to be used independently for lipid management evaluation.
A multi-center clinical trial is now underway in three hospitals in China, says Wang. “For this product, we are also providing information to the China Food and Drug Administration for review, and it is expected that the medical device registration certificate can be obtained as soon as 2023.” After that, certification by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency could potentially be pursued.
The new skin cholesterol test has one close comparison product—Cholesterol 1, 2, 3, which determines patients’ cholesterol in the skin using the palm of their hand. It was approved by the FDA in 2002 specifically for adults with severe coronary artery disease who are already at high risk of heart attack.
Previous studies provide a basis for the optimization of skin cholesterol detection systems, says Wang, referencing a 2013 review published in the Canadian Journal of Cardiology (DOI: 10.1016/j.cjca.2013.04.007) that looked at nine cohorts reported in 11 studies.
The studies suggest skin cholesterol levels do not correlate with traditional markers of cardiovascular disease but have a significant relationship with underlying atherosclerosis. All these studies were performed in Europe using a handheld in-situ test, in contrast to the “no-touch palm measurement device” Wang and his colleagues are proposing.
“Compared to in-situ detection used in the previous clinical research, our device may offer more accurate results for we can avoid the influence of pressure and skin background differences [person to person],” says Wang. Study results offer the first evidence of a relationship between skin cholesterol and atherosclerotic disease in a Chinese population, which “may be of great significance” to researchers around the world.
The novel testing instrument contains detection instruments and a reagent related to a fluorescent group that specifically binds to skin cholesterol at the detection site, explains Wang, noting that the amount of binding reagent on the skin surface is positively correlated with cholesterol content. When the test site gets irradiated with excitation light of a specific wavelength, the fluorescence spectrum can be inverted to indicate skin cholesterol content.
The entire detection process only takes about three or four minutes, he says. But production of the system has been a “highly integrated product of chemistry, optics, medicine, and other disciplines,” and has involved overcoming many technical difficulties.
Design of the skin cholesterol fluorescent probe was the first challenge, continues Wang. Researchers also had to figure out how to extract a weak fluorescent signal, since skin cholesterol content is relatively low.
“Our research found for the first time that after taking lipid-lowering drugs… blood cholesterol and skin cholesterol both showed a [consistent] downward trend,” Wang says. The results suggest that skin cholesterol might be used to replace blood cholesterol testing for cardiovascular disease screening and patient medication evaluation.
“Cholesterol readings produced by the device are not significantly related to traditional blood lipid results,” he continues. “Actually, they are cholesterol in two different states. Blood cholesterol is combined with apolipoprotein, and skin cholesterol is cholesterol deposited in the skin. Both previous reports and our results confirm that these two kinds of cholesterol do not have a strong correlation ... [but are] closely related to the occurrence and development of atherosclerotic cardiovascular disease.”
To date, only preclinical studies have been conducted to determine the indications for formal clinical trials in the future, says Wang. At that later stage, researchers will focus more on “miniaturization, intelligence, and integration of equipment.” Clinical studies will launch after some improvement work on the system and the final product form is determined.
The skin cholesterol detection system as presently designed would mainly be suitable for use as a decision support tool in doctors’ offices, he adds, but it is “very likely” that it will ultimately be turned into a portable device.
As with all diagnostic techniques, device operation determines accuracy of test results, says Wang. “A critical step in the [testing] process that is subject to operator variability is blotting, which requires the operator to remove an unbound detector from the palm before adding the indicator. Excess residual indicator solution can result in falsely increased skin cholesterol levels. Considering this, we are planning to develop a simplified and standardized blotting procedure.”
Frequency of system use will be based on the number of patients in a clinical department, he says. For cardiovascular disease screening, testing once every six months is recommended and, for cardiovascular patient medication evaluation, once every two weeks.
The focus is currently on populations at high risk of arterial sclerosing cardiovascular disease, for screening, and those with cardiovascular disease taking lipid-lowering drugs, for blood lipid management and evaluation of medication effect, Wang adds.
In the process of testing, disposables like cleaning towels, limit pads, and water-absorbing sticks are needed, he says. The approximate cost of these items is less than $16, including the detection reagent.