Magdalena Krintus

Background: Despite its growing impact, advanced liver fibrosis (ALF) remains substantially underdiagnosed in both primary and specialized care settings. Since liver cirrhosis is typically preceded by a prolonged phase of asymptomatic fibrosis, early detection of ALF, particularly in high-risk individuals, represents a public health priority. From a laboratory medicine perspective, this prolonged subclinical phase offers an interesting opportunity for early detection of ALF using blood-based noninvasive tests (NITs) that can be implemented in primary and nonhepatology care settings before overt disease develops. Content: By critically appraising the evidence sources in the available literature, this paper provides an overview of blood-based NITs useful for the detection of ALF, with particular emphasis on the aspects and problems related to their implementation in daily laboratory practice. We explore the feasibility of different scenarios using strategies based on routine biochemical parameters and more specialized NITs that incorporate measurements of direct markers of fibrosis activity. Moreover, we highlight discrepancies existing among clinical practice guideline (CPG) recommendations that may hamper their widespread implementation in medical laboratories. Summary: Advances in understanding and increase in prevalence of ALF require earlier detection and more accurate risk assessment of this condition. Blood-based NITs may provide a widely accessible diagnostic aid, especially in primary care and resource-limited settings. Multidisciplinary collaboration focusing on their integration into clinical pathways to optimize patient evaluation and specialist referral is required. Harmonization of recommendations in international CPGs will certainly contribute to their more effective use.

Background: The diagnosis of hypercholesterolemia relies on the laboratory assessment of lipid parameters. This study aimed to evaluate differences in the distribution of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) concentrations according to the presence and type of lipid-lowering therapy (LLT). Methods: This retrospective analysis included consecutive patients who had at least one measurement of LDL-C, apoB, and non-HDL-C between March and November 2024 in a high-volume tertiary hospital. All lipid fractions were expressed as the percentages of measurements above or below cut-off values established by the recent ESC guidelines. Subgroup analysis based on LLT type was performed, with patients categorized as receiving either single or combined LLT. Results: A total of 5048 patients were included in the analysis. Among patients receiving LLT, most were on statin monotherapy (77.3%), predominantly atorvastatin. Combined therapy, primarily statin plus ezetimibe, was used in 22.7% of treated patients. Discordance between on-target apoB levels and elevated LDL-C concentrations occurred in 26.6% of untreated and 13.6% of all treated patients, and in 15.1% and 8.6% of single and combined-LLT patients, respectively. Similarly, discordance between on-target non-HDL-C and elevated LDL-C levels was observed in 13.5% of untreated and 7.5% of all treated patients, and in 8.4% and 4.8% of single and combined-LLT patients, respectively. Conclusions: Classification of hyperlipidemia based on LDL-C, non-HDL-C, and apoB concentrations reveals significant discrepancies between these markers, especially between LDL-C and apoB. LLT reduces these discrepancies with combined LLT being particularly effective.

Background: Recent studies have indicated that serum calprotectin, a marker of inflammation, is associated with obesity and disorders of glucose and lipid metabolism. The aim of this study was to evaluate the relationship between serum calprotectin and cardiometabolic risk factors in presumably healthy young adults. Methods: The study enrolled 118 (61 females, 57 males) non-obese, normoglycemic, subjects aged 25–40 years, selected from the general population among participants of the diabetes preventive screening program in 2014–2015. Basic anthropometric measurements and the following laboratory tests were performed on all participants: glucose, glycated hemoglobin (HbA1c), lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), calprotectin and adiponectin. Results: The serum calprotectin concentration was significantly higher in men compared to women (p = 0.016), and in overweight subjects (p < 0.001) and those with abdominal obesity (p < 0.001), compared to lean individuals. Serum calprotectin was positively correlated with body mass index (BMI), waist circumference, HbA1c, hs-CRP, insulin, HOMA-IR and triglycerides, and negatively with HDL-cholesterol and adiponectin. In the univariable logistic regression analysis, overweight (OR = 2.529; p = 0.015), abdominal obesity (OR = 3.217; p = 0.006), hs-CRP > 1 mg/L (OR = 5.00; p < 0.001), HOMA-IR > 2.0 (OR = 4.394; p < 0.001), and HbA1c > 32 mmol/mol (OR = 2.166; p = 0.021) were significant predictors of increased calprotectin concentration (≥540.8 ng/mL; ≥median). However, in models adjusted for sex, BMI and hs-CRP, the significant association remained only for increased HbA1c and HOMA-IR values. Conclusions: Association of serum calprotectin with overweight, hs-CRP and laboratory indicators of glucose metabolism and insulin resistance suggest its significance as a laboratory biomarker of initial metabolic impairment.

Background: Recent studies suggest that erythroferrone (ERFE), an iron-regulating protein whose primary role is to inhibit hepcidin synthesis, may affect glucose and lipid metabolism, and its serum concentration is reduced in obese and diabetic individuals. The aim of this study was to evaluate the association of ERFE concentration with selected cardiometabolic risk factors in apparently healthy young adults. Methods: This preliminary study consisted of 122 (63 females, 59 males) normoglycemic, non-smoking subjects aged 25–40 years. In all participants, anthropometric measurements and the following laboratory tests were performed: fasting plasma glucose, glycated hemoglobin (HbA1c) and serum iron, lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), ERFE and hepcidin. Results: The serum ERFE concentration was significantly lower in men compared to women (p = 0.009) and in subjects who were overweight (p < 0.001) and had abdominal obesity (p < 0.001). ERFE showed significant negative correlations with body mass index, waist–hip ratio, HbA1c, CRP, insulin, HOMA-IR and triglycerides. In the logistic regression analysis, ERFE was significantly associated with being overweight (OR = 0.051; p = 0.004), abdominal obesity (OR = 0.372; p < 0.001), HOMA-IR ≥ 2.0 (OR = 0.584; p = 0.013), CRP > 1 mg/L (OR = 0.648; p = 0.020) and triglycerides (OR = 0.521; p = 0.033). A relevant predominance in the prevalence of cardiometabolic risk factors was observed in subjects with ERFE levels in the first tertile (2.19 ng/mL). Conclusions: Serum ERFE is inversely associated with being overweight, increased waist circumference, CRP, and markers of insulin resistance and lipid abnormalities, suggesting its potential relevance as a marker of early cardiometabolic risk in apparently healthy young adults.

Hyperlipidemia is the most prevalent cardiovascular (CV) risk factors. We aimed to analyze the distribution of lipid parameters and clinical variables associated with elevated and non-elevated selected lipid factors in a cohort of all consecutive patients whose lipid profile was assessed at a multi-specialist clinical center. This cross-sectional study analyzed electronic medical records of consecutive patients treated between March and November 2024. Lipid parameters measured included: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (apoB), and lipoprotein (a) [Lp(a)]. Non-high-density lipoprotein cholesterol (non-HDL-C) was calculated as TC–HDL-C. We used multivariate analysis to identify factors associated with LDL-C, TG, and Lp(a) concentrations. A total of 10,597 patients were included in the analysis. The median lipid concentrations (mg/dL) were: TC 162 (IQR 132–198), LDL-C 94 (IQR 69–129), non-HDL-C 112 (IQR 88–146), apoB 78 (IQR 63–99), and Lp(a) 11 (IQR 5–29). Elevated LDL-C > 100 mg/dL was observed in 45.7% of patients, non-HDL-C > 130 mg/dL in 35.1%, and apoB > 100 mg/dL in 23.2%. A discordance between LDL-C and apoB concentrations was present in 23.7% of patients (p < 0.001), while LDL-C/non-HDL-C and apoB/non-HDL-C discordance rates were 13% and 12.6%, respectively (p < 0.001). Patients at very high CV risk had lower TC, LDL-C, non-HDL-C, and apoB concentrations compared to those with low-to-moderate and high CV risk (p < 0.001) and showed the highest median Lp(a) concentration of 13 mg/dL (IQR 5–31; p = 0.01). Goal achievements of LDL-C < 100 mg/dL, TG < 150 mg/dL, and Lp(a) < 30 mg/dL were associated with lipid-lowering treatment [OR 1.32 (95% CI 1.12–1.52)], atrial fibrillation [OR 1.31 (95% CI 1.11–1.54)], chronic coronary syndromes [OR 1.27 (95% CI 1.05–1.52)], smoking [OR 0.78 (95% CI 0.65–0.95)], BMI [OR 0.98 (95% CI 0.96–0.99)], and age [OR 1.006 (95% CI 1.002–1.009)]. The highest proportion of patients with results within the normal range was observed for apoB and the lowest for LDL-C. The highest discordance was observed between apoB/LDL-C, with similar discordance rates between LDL-C/non-HDL-C and apoB/non-HDL-C. Lipid profile control was associated with BMI, atrial fibrillation, age, chronic coronary syndrome, aortic stenosis, diabetes, male gender, lipid-lowering therapy, and smoking. These findings highlight the complexity of lipid management.

Background: Low but detectable cardiac troponin (cTn) concentrations may reflect cardiovascular (CV) risk in a primary prevention setting. Using previously described thresholds for CV risk stratification, we assessed the influence of sex and cardiometabolic risk factors on the concentrations of high-sensitivity cTn in presumably healthy subjects. Methods: The prospective study included 597 presumably healthy individuals (313 women, 284 men). In all participants, hs-cTnI, hs-cTnT, lipid profile, C-reactive protein, glycated hemoglobin, estimated GFR (eGFR) and B-type naturetic peptide (BNP) were measured. Subjects were categorized into two groups of CV risk, based on hs-cTn non sex-specific cut-off of 5.0 ng/L. For hs-cTnI, sex-specific cut-off values were also used: ≥4.0 ng/L for females and ≥6.0 ng/L for males. Results: Increased CV risk, indicated by hs-cTn concentrations ≥ 5.0 ng/L, was significantly associated with age > 40 years, male sex, obesity and BNP concentrations ≥ 35 ng/L. Using the same 5.0 ng/L threshold, hs-TnT classified approximately twice as many individuals into the CV subgroup compared to hs-cTnI, particularly in males (31% vs. 13%, respectively). After applying sex-specific cut-offs for hs-cTnI, the proportion of females and males with increased risk became similar (8% vs. 9%, respectively). In contrast, using non-sex-specific cut-offs for hs-cTnI resulted in a proportion of 6% for females and 13% for males. BNP and eGFR had significant impact on CV risk stratification using sex-specific cut-offs for hs-cTnI. Conclusions: Our findings suggest the necessity of using sex-specific cut-offs for hs-cTn as a cardiovascular risk marker, in addition to other cardiometabolic factors, in the general population.

Article Adult reference intervals for serum thyroid‐stimulating hormone using Abbott Alinity i measuring system was published on October 9, 2024 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 0, issue 0).

Background: Elevated lipoprotein (a) [Lp(a)] concentrations are linked mainly to genetic factors. The relationship between Lp(a) and other lipid disorders or cardiovascular (CV) risk factors has been less investigated. The aim of this study was to assess the occurrence of lipid disorders and other CV risk factors according to Lp(a) concentrations. Methods: A cross-sectional analysis of 200 primary-care patients who had not been diagnosed with CV disease was conducted. The following risk factors were assessed: older age, history of hypertension, diabetes mellitus or dyslipidemia, smoking, lack of physical activity, body mass index (BMI), and waist circumference. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and small, dense LDL (sdLDL-C). Patients were divided into two groups based on their Lp(a) concentrations: p = 0.04), with no significant differences regarding the other analyzed lipid disorders (p > 0.05). Both in the low- and high-Lp(a) group, most patients had two other abnormal lipid factors (45.0% and 60.0%, respectively). The distribution of impaired lipid parameters (p = 0.41) and other CV risk factors (p = 0.16) was similar in both groups. There was a lower rate of patients >60 years old (15.0% vs. 32.9%, p = 0.01) and with a BMI ≥ 25 kg/m² (46.7% vs. 63.6%, p = 0.026) in the high-Lp(a) group, and previously diagnosed hyperlipidemia was more prevalent in this group (65.0% vs. 47.1%, p = 0.02). The occurrence of other cardiovascular risk factors did not differ significantly between the Lp(a) groups (p > 0.05). In the high-Lp(a) group, the highest proportion (25.0%) had two CV risk factors, and in the low-Lp(a) group, 31.4% had four CV risk factors. Conclusions: An elevated Lp(a) concentration is not related to the number of conventional CV risk factors or other impairment major lipid parameters.