Point-of-care testing compared to gold-standard laboratory methods in the measurement of serum lipids.

BACKGROUND: Cardiovascular disease is the leading cause of mortality worldwide, with dyslipidaemia being one of the major risk factors. Point-of-care testing (POCT) allows for the rapid measurement of serum lipids. The aim of this study was to assess the accuracy of serum lipid measurement by the Fujifilm™ NX700 POCT compared to a gold-standard clinical laboratory method (Medpace, Leuven, Belgium). METHODS: This was a prospective, observational study conducted at the Lipid Clinic at Charlotte Maxeke Johannesburg Academic Hospital from July to September 2022. Participants were known to have a lipid disorder, most commonly, familial hypercholesterolaemia. Samples sent for lipid measurement by standard laboratory methods were simultaneously measured by the Fujifilm™ NX700 POCT. RESULTS: Lipograms evaluating total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and calculated low-density lipoprotein cholesterol (LDL-C) were obtained from 115 participants. No statistically significant difference was noted between the parameters tested on the different platforms. The Fujifilm™ NX700 POCT correctly identified > 91% of serum lipid results as normal or abnormal, as defined by NCEP-ATP III criteria, and exhibited good sensitivity and specificity for each parameter. Lin's concordance correlation coefficient demonstrated a strong correlation for all parameters; TC (ρc = 0.9861), HDL-C (ρc = 0.95919), LDL-C (ρc = 0.98134) and TG (ρc = 0.92775). Bland-Altman plots identified low bias and a good level of agreement between the two test methods. CONCLUSION: The Fujifilm™ NX700 POCT compared favourably with gold-standard laboratory methods in the determination of serum lipid measurements, allowing for rapid screening at the primary healthcare level.

Cascade Screening for Familial Hypercholesterolemia in South Africa: The Wits FIND-FH Program.

OBJECTIVE: Due to gene founder effects, familial hypercholesterolemia (FH) has a prevalence of ≈1:80 in populations of Afrikaner ancestry and is a major contributor to premature atherosclerotic cardiovascular disease in South Africans of Jewish and Indian descent. No systematic program exists to identify these families. Furthermore, information regarding FH prevalence in Black Africans is sparse. The Wits FIND-FH program was initiated in late 2016 to address these issues. Approach and Results: Based on index subjects with definite or probable FH, first-degree relatives were contacted, informed consent obtained, and targeted medical history, physical examination, and blood samples collected. In patients with likely FH using the Simon Broome criteria, DNA analysis for LDLR (low-density lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase subtilisin/kexin type 9), and LDLRAP1 (LDLR adaptor protein 1) variants was analyzed by next-generation sequencing. Of the initial 700 subjects screened of whom 295 (42%) were index cases, 479 (68.4%) were clinically diagnosed with probable or definite FH. Genetic analysis confirmed 285 of 479 (59.5%) as having variants consistent with FH. Three subjects met the clinical diagnosis for homozygous FH, but DNA analysis revealed a further 34 patients, including 4 Black African subjects, with ≥2 FH-causing variants. CONCLUSIONS: Using phenotype cascade screening, the Wits FIND-FH program has screened an average of 30 subjects monthly of whom 68% had a clinical diagnosis of FH with ≈60% genetically confirmed. The program is identifying a small but growing number of Black South Africans with FH. Interestingly, 37 subjects (7.7%) who underwent DNA testing were found to have ≥2 FH-causing variants.

Complementary Impact of Carotid Intima-Media Thickness With Plaque in Associations With Noncardiac Arterial Vascular Events.

The ability of carotid intima-media thickness (IMT) to predict risk beyond plaque is controversial. In 952 participants (critical limb ischemia [CLI] or stroke, n = 473; community, n = 479), we assessed whether relationships with events for IMT complement the impact of plaque in young patients depending on the extent of thrombotic versus atherosclerotic disease. The extent of atherosclerotic versus thrombotic occlusion was determined in 54 patients with CLI requiring amputations. Thrombotic occlusion in CLI was associated with younger age (P < .0001) and less plaque (P = .02). Independent relations between plaque and CLI were noted in older (>50 years; P < .005 to <.0001) but not younger (P > .38) participants, while independent relations between plaque and stroke (P < .005 to <.0001) and between IMT and CLI (P < .0001) were noted in younger participants. Although in performance (area under the receiver operating curve) for event detection, IMT thresholds failed to add to plaque alone in older patients (0.680 ± 0.020 vs 0.664 ± 0.017, P = .27), IMT improved performance for combined stroke and CLI detection when added to plaque in younger patients (0.719 ± 0.023 vs 0.631 ± 0.026, P < .0001). Because in younger participants the high prevalence of thrombotic occlusion in CLI is associated with less plaque, IMT adds information in associations with arterial vascular events.

The carotid artery atherosclerosis burden and its relation to cardiovascular risk factors in black and white Africans with established rheumatoid arthritis: a cross-sectional study.

OBJECTIVE: Black Africans currently experience a distinctly low frequency of atherosclerotic cardiovascular disease. Whether this protection persists in those with rheumatoid arthritis (RA) is unknown. We compared the carotid atherosclerosis burden and its relationships with cardiovascular (CV) risk factors between Africans with RA from a developing black and developed CV population. METHODS: We performed high resolution B-mode ultrasonography and assessed CV risk factors in 243 patients with established RA, of whom 121 were black and 122 white. Data were analyzed in age, sex, and healthcare center-adjusted regression models. RESULTS: The mean±SD common carotid intima-media thickness (cIMT) was 0.694±0.097 mm in black and 0.712±0.136 mm in white patients (adjusted p=0.8). Plaque prevalence was also similar in black compared to white cases (35.5% and 44.3%, respectively; adjusted OR 0.83, 95% CI 0.32-2.20, p=0.7). Interactions between population grouping and several CV risk factors were independently associated with cIMT and plaque. In stratified analysis, that is, in each population group separately, risk factors associated with cIMT or/and plaque comprised the systolic blood pressure (p=0.02), serum cholesterol/high-density lipoprotein cholesterol ratio (p=0.004), C-reactive protein concentrations (p=0.01), and the presence of extraarticular manifestations (p=0.01) in whites but, contrastingly, the Arthritis Impact Measurement Scales tension score (p=0.04) and use of nonsteroidal antiinflammatory agent (p=0.03) in black patients. The Framingham score was significantly associated with atherosclerosis only in whites (p<0.0001). CONCLUSION: The carotid atherosclerosis burden is similar in black compared to white Africans with RA, but relationships between modifiable CV risk factors and atherosclerosis vary substantially among Africans with RA.

Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis.

OBJECTIVE: To determine the association between cardiovascular (CV) risk factors and atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: The common carotid artery intima-media thickness (IMT) and plaque were evaluated by high resolution B-mode ultrasound in 74 consecutive patients with RA. Patients with an IMT > or = 0.60 mm and plaque were considered to have atherosclerosis and advanced atherosclerosis, respectively. Traditional risk factors as well as an extensive range of other clinical and laboratory variables were recorded. Methods used to analyze the data included logistic regression, classification and regression tree (CART), and factor analyses. RESULTS: Fifty-three (72%) patients had atherosclerosis, 23 (31%) had plaque, and 21 (28%) were free of atherosclerosis. In multivariable analysis, age and hypertension were independently associated with atherosclerosis and plaque (p < or = 0.04). Radiographic scores and polymorphonuclear cell counts were also strongly associated with plaque (p < or = 0.008). Uric acid concentrations were associated with atherosclerosis, and hypothyroidism was associated with plaque, both with borderline significance (p = 0.078 and 0.052, respectively). In CART analysis, age, polymorphonuclear cell counts, and joint space narrowing in the hands were considered to be the most important determinants of plaque, and 62% of patients could be classified correctly after cross-validation. Factor analysis (varimax rotation) revealed that age and uric acid levels were related to low glomerular filtration rates, polymorphonuclear cell counts to disease activity, and radiographic scores to disease duration, and hypertension was associated with high cholesterol levels. The 10-year risk for a coronary event estimated using the Framingham risk equation (calculated from traditional risk factors) was only 7% in patients with plaque. CONCLUSION: Atherosclerosis in RA is associated with the traditional CV risk factors age and hypertension, as well as nontraditional risk factors comprising current inflammation as reflected by polymorphonuclear cell counts, cumulative inflammation as disclosed by radiographic scores, and, to a lesser extent, with uric acid levels and hypothyroidism. Multiple risk factor assessment equations that are based on traditional risk factors only are likely to be insufficient to capture CV risk extent in RA.

High-dose atorvastatin therapy is required for significant improvement of endothelial function in heterozygous familial hypercholesterolaemic patients.

This study evaluated endothelial dysfunction (ED) by measuring flow-mediated vasodilation (FMD) and for six months documented changes in ED, LDL-C levels and serum concentrations of inflammatory markers with high- and low-dose atorvastatin therapy. In 23 heterozygous familial hypercholesterolaemic (FH) patients, FMD, LDL-C and inflammatory markers (sVCAM-1, sICAM-1, E-selectin and highly sensitive C-reactive protein) were measured at baseline (untreated) and on atorvastatin 20 and 80 mg/day. In untreated patients, FMD was significantly reduced (mean +/- SD = 3.09 +/- 0.91%) compared with 10 normocholesterolaemic controls (8.71 +/- 2.41%; p < 0.01). FMD improved non-significantly with atorvastatin 20 mg/day (5.60 +/- 1.17%), but showed a significant improvement (8.54 +/- 1.11%; p < 0.01) with atorvastatin 80 mg/day. LDL-C decreased markedly (-42.4%; p < 0.0001) on 20 mg/day and decreased further (-48.6%; p < 0.05) on 80 mg/day. FMD improvement, however, did not correlate with LDL-C reduction. No significant changes occurred in any inflammatory markers. We concluded that ED was present in untreated FH patients and improved significantly on high-dose atorvastatin. There was no correlation between the changes in FMD and LDL-C, suggesting either a LDLC-independent effect on ED, or that a marked reduction in LDL-C is required to normalise ED in FH.