The use of telemedicine for prehospital diagnosis and triage of patients directly to the catheter laboratory is feasible and allows 89% of patients living up to 95 km from the invasive centre to be treated with PPCI within 120 min of the emergency medical service call. The study confirms that a recommendation of a system delay <60 min is unachievable if the FMC is the emergency medical call.

Background: Studies indicate that human peripheral blood mononuclear cells mirror low‐density lipoprotein (LDL) receptor activity of other cells in the body. To measure LDL receptor activity in patients with heterozygous familial hypercholesterolemia (FH), we prepared peripheral blood mononuclear cells from individuals with molecularly verified LDL receptor defective (Trp66‐Gly mutation, n = 18) or receptor negative (Trp23‐stop mutation, n = 17) heterozygous FH and from healthy individuals (n = 24). Methods: The cells were stimulated to express maximum LDL receptor by preincubation in lipoprotein‐free medium. They were then incubated at 4° or 37°C with fluorescently conjugated LDL (DiI‐LDL). T‐lymphocytes and monocytes were identified by fluorescently conjugated monoclonal antibodies. DiI‐LDL bound (at 4°C) or internalized (at 37°C) by the cells was measured using flow cytometry. Knowing the LDL receptor gene mutation of the FH patients allowed us to compare the diagnostic capability of our functional assay with the DNA diagnosis. Results: The diagnostic accuracy did not allow our assay to be used for diagnosis of individual cases of heterozygous FH. Conclusions: We suggest that our two‐color fluorescence flow cytometry assay can be used to characterize functionally gene mutations causing LDL receptor dysfunction in patients with heterozygous FH. Cytometry 36:52–59, 1999. © 1999 Wiley‐Liss, Inc.

We used a fluorescence flow cytometry assay with a monoclonal low density lipoprotein (LDL) receptor-specific antibody to detect LDL receptor expression on blood T lymphocytes and monocytes. We prepared peripheral blood mononuclear cells from patients with genetically verified LDL receptor-defective (Trp66-Gly mutation, n = 17) or receptor-negative (Trp23-stop mutation, n = 17) heterozygous familial hypercholesterolemia (FH) and from healthy individuals (n = 24). The cells were stimulated to express the maximum amount of LDL receptor by preincubation in lipoprotein-deficient medium. A dual-labeling technique allowed flow cytometric analysis of LDL receptor expression on cells identified by fluorescently conjugated surface marker antibodies. Knowing the LDL receptor gene mutation of the FH patients allowed us to compare the diagnostic capability of this functional assay with the DNA diagnosis and to validate the assay with molecular genetics instead of clinical indices of heterozygous FH. T lymphocytes expressed more LDL receptors and gave better diagnostic results than monocytes, and cells from patients with either the Trp66-Gly or the Trp23-stop mutation had variable but significantly reduced LDL receptor expression. The data indicate that this fluorescence flow cytometry assay is unsuitable for diagnosis of individual cases of heterozygous FH but that it may be useful for functionally characterizing mutations in the LDL receptor gene.

Abstract. Jensen JM, Gerdes LU, Jensen HK, Christiansen TM, Brorholt-Petersen JU, Faergeman O (Aarhus Amtssygehus University Hospital, Aarhus, Denmark). Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia. J Intern Med 2000; 247: 479±484.Objectives. Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD: traditional risk factors of CHD (age, sex, cholesterol, hypertension, smoking and body mass index), cholesterol year score, and aortic as well as coronary calcium measured by spiral computed tomography (CT).Subjects. We invited 88 individuals with molecularly defined FH of whom 80 (91%) decided to participate. Results. Analysis of receiver operating characteristic curves showed that the age-adjusted coronary calcium score was more strongly associated with clinical manifestations of CHD than were traditional risk factors (P , 0.002), cholesterol year score (P ,, 0.0001), and the age-adjusted aortic calcium score (P , 0.0004). Conclusions. Age-adjusted coronary calcium score shows promise as an indicator of CHD in FH patients.

We report a functional characterization of the W23X and W66G low density lipoprotein (LDL) receptor gene mutations. The authors used two-color fluorescence flow cytometry to measure LDL receptor activity in stimulated T-lymphocytes, prepared from patients heterozygous for the W23X or W66G mutation, and compared the results with measurements of LDL receptor activity in stimulated T-lymphocytes prepared from unrelated healthy control subjects. It was found that the W23X mutation significantly reduced LDL receptor expression and LDL binding and internalization, and that the W66G mutation significantly reduced LDL receptor expression and LDL binding. LDL internalization in patients heterozygous for the W66G mutation was not significantly reduced. The data support the concepts that the W23X mutation prevents production of LDL receptors (class I) and that the W66G mutation produces LDL receptors unable to recycle normally in cells (class V).