Postprandial chylomicron remnant clearance was studied in six patients with familial combined hyperlipidemia (FCH) and seven control subjects by using an oral retinyl palmitate (RP) fat-loading test The chylomicron remnant clearance (S,< 1,000 fraction), expressed as the area under the RP curve (AUC-RP), was delayed in FCH subjects (65.05 ±12.84 hours x [mg/L]) compared with control subjects (25.1±5.4 hoursx[mg/L]; p=0.01). Postprandial lipoprotein particle size and composition in the Sf> 1,000 fraction were different between FCH and control subjects as analyzed by molecular-sieve chromatography. Fasting high density lipoprotein cholesterol was lower in FCH patients (0.54 ±0.09 mmol/L) than in control subjects (0.89±0.05 mmol/L; p<0.01). Mean plasma postheparin lipoprotein lipase and hepatic lipase activities were similar between FCH patients (94 ±25 and 427 ±57 milliunits/mL, respectively) and control subjects (126±16 and 362±33 milliunits/mL, respectively). In FCH, a 54% reduction (p<0.05) of plasma triglycerides to 2.63±0.41 mmol/L by drug treatment resulted in an enhanced, but not normalized, clearance of chylomicron remnants (39.4±6.0 hours x [mg/L]). Univariate regression analysis revealed that in FCH subjects the changes in fasting plasma apolipoprotein C-III concentrations after therapy were significantly associated with the changes in chylomicron remnant AUC-RP (r=0.87;p=0.02). Delayed elimination of atherogenic chylomicron remnants may contribute to the increased risk of premature atherosclerosis in FCH. ( of premature atherosclerosis in FCH patients has been related to the observed lipoprotein abnormalities. However, neither elevated low density lipoprotein (LDL) concentrations nor decreased high density lipoprotein (HDL) levels are consistently found in all FCH patients. 4 Increased production of VLDL and VLDL remnants in FCH patients may be important, since remnants are atherogenic particles that contribute to premature atherosclerosis.8 " 12 We studied postprandial lipoprotein metabolism in six patients with FCH and seven normolipidemic control subjects. Because postprandial chylomicron metabolism is known to depend on fasting plasma TGs, 10 -13 apo B, 13 and HDL 2 cholesterol, 14 the FCH patients were studied both before and after lipid-lowering medication. We used the oral retinyl palmitate (RP) fat-loading test 1015 in separate studies of the elimination of chylomicrons and chylomicron remnants. Methods FCH PatientsThe six male FCH patients (aged 30-66 years) were on a low-fat, low-cholesterol diet, 16 comparable to the American Heart Association Phase I diet, and did not consume more than four alcoholic beverages per week. Patients were diagnosed as FCH when they had each of the following: 1) hyperlipidemia, defined as cholesterol and/or TG plasma concentrations >6.5 and 2.0 mmol/L, respectively, 2) at least one first-degree relative with a different lipoprotein phenotype than the index patient 5 ; 3) an elevated fasting plasma concentration of apo B (>0.9 by guest on May 9, 2018 http://atvb.ah...

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SummaryLipoprotein(a) [Lp(a)] is recognized as an independent risk factor for atherosclerosis. Lp(a) consists of a LDL-like moiety with an additional glycoprotein, apo(a), linked to apolipoprotein B-100. Apo(a) has a high homology with plasminogen (Pg). In vivo, Pg is activated on a fibrin surface by tissue Pg activator (tPA). We prepared Lp(a) from plasma by sequential ultracentrifugation followed by lysine-sepharose affinity chromatography. We found that a changing (donor dependent) fraction of the Lp(a) did not bind to lysine-sepharose. This fraction, designated Lp(a)lys–, was further purified using gel filtration. Bound Lp(a) [Lp(a)lys+] was eluted with 0.2 M EACA. Apo(a) isoforms in both fractions were identical. In contrast Lp(a)lys+ inhibited Pg activation by tPA in vitro (IC50% 20 mg/1), whereas Lp(a)lys– did not. In addition Lp(a)lys– did not bind to CNBr-digested fibrinogen whereas Lp(a)lys+ did (K d, app = 0.2 nM). Therefore we conclude that a changing donor dependent fraction of human plasma Lp(a) does not inhibit Pg activation in vitro and does not bind to CNBr-digested fibrinogen.

To find out why most patients with the nephrotic syndrome maintain a normal blood volume despite a reduced plasma colloid osmotic pressure (COP), we measured the transcapillary (plasma-tissue fluid) COP difference in 12 patients with the nephrotic syndrome, as well as in 6 patients during complete (n = 3) and partial (n = 3) recovery. Subcutaneous nylon wicks were used to collect tissue fluid. The albumin content was also measured. The albumin content and COP were lowered in both plasma and tissue fluid in the nephrotic phase, and rose gradually during recovery. During these changes the transcapillary COP difference only rose slightly: from 6.2 ± 1.7 mm Hg when the plasma COP was below 10 mm Hg (n = 11) to 8.7 ± 1.5 mm Hg when the plasma COP exceeded 20 mm Hg (n = 12). These observations indicate that in hypoproteinemia preservation of the intravascular volume is strongly dependent on maintenance of the difference in oncotic pressure across the capillary wall.