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Biomedical subjects

G E Gilbert

Publications and source records attributed to G E Gilbert.

At least 19 recordsLinked to original sources
PubMed2000

Amphipathic helices support function of blood coagulation factor IXa.

Blood coagulation factor IXa gains proteolytic efficiency upon binding to a phospholipid membrane. We have found that an amphipathic, membrane-binding peptide from the C2 domain of factor VIII, fVIII(2303)(-23), enhances proteolytic efficiency of factor IXa in the absence of phospholipid membranes. This enhancement is the result of a reduction in the K(M) for the substrate, factor X, with little effect on the k(cat). Enhanced function requires interaction of the gamma-carboxyglutamic acid (Gla) domains of factor IXa and factor X since (i) a synthetic peptide comprising the Gla domain of factor IXa and antibodies directed to the Gla domain of factor IXa inhibit this acceleration, (ii) the acceleration is Ca(II) dependent, and (iii) conversion of Gla-domainless factor X is not affected by the presence of fVIII(2303)(-23). The effect of fVIII(2303)(-23) on factor IXa parallels the enhanced function produced by phosphatidylserine-containing bilayers, and fVIII(2303)(-23) does not further enhance function of factor IXa when phospholipid vesicles are present. The critical feature of fVIII(2303)(-23) is apparently its amphipathic helix-forming structure [Gilbert, G. E., and Baleja, J. D. (1995) Biochemistry 34, 3022-3031] because other alpha-helical peptides such as a homologous peptide from the C2 domain of factor V and melittin have similar effects. Diastereomeric analogues of fVIII(2303)(-23) and melittin, which have reduced helical content, do not support factor IXa activity. A truncated peptide of fVIII(2303)(-23) with three C-terminal residues deleted retains alpha-helical content but loses capacity to enhance factor X cleavage, suggesting that a minimum length of alpha-helix is required. Although these results probably do not illuminate the physiologic function of the factor VIII peptide corresponding to fVIII(2303)(-23), they demonstrate a novel, membrane-mimetic role of amphipathic helical peptides in supporting function of factor IXa.

1-Carboxyglutamic Acid↗
PubMed2000

The ability of a medical school admission process to predict clinical performance and patients' satisfaction.

PURPOSE: The authors evaluated the ability of a two-step admission process to predict clinical performance and patients' satisfaction on a third-year objective structured clinical examination (OSCE). METHOD: Subjects were three matriculating classes (1993, 1994, 1995) at one medical school. Data for the classes were analyzed separately. Independent variables were the Academic Profile (AP), an initial ranking of applicants based on grade-point ratio and MCAT scores, and the Selection Profile (SeP), an average of three interview scores. Interviews were offered based on AP rank, and admission was offered based on SeP rank. Dependent variables were total score on the faculty-graded portion of the OSCE and patients' satisfaction scores completed by the OSCE standardized patients. The authors evaluated the correlations between AP and OSCE performance and between SeP and OSCE performance. The authors also compared the OSCE performances of students whose ranks changed after interviews (SeP rank < AP rank or SeP rank > AP rank). The level of significance was adjusted for the number of comparisons (Bonferroni method). RESULTS: Complete data were available for 91% of eligible students (n = 222). No class showed a significant correlation between either AP or SeP rankings and OSCE performance (p > .01). Likewise, there was no difference in OSCE performance for students whose ranks changed after the interview. CONCLUSIONS: The admission ranking and interview process at this medical school did not predict clinical performance or patients' satisfaction on this OSCE.

Achievement↗
PubMed2000

Responding to patients' emotions: important for standardized patient satisfaction.

BACKGROUND AND OBJECTIVES: Several experts have emphasized the need to respond to a patient's emotions as an essential component of effective medical interviewing. This study examined the relationship of faculty observers' scores of students' performance in standardized patient (SP) interviewing stations in a family medicine clerkship objective structured clinical examination (OSCE) with SP satisfaction measures. METHODS: The faculty observers scored students in the following performance domains: 1) interviewing skills, 2) negotiating the diagnosis or plan, 3) gathering case-specific content information, 4) responding to the patient's emotions, and 5) student's overall performance. Pearson Product-Moment correlations were calculated for each of these domains and the Standardized Patient Satisfaction Questionnaire (SPSQ) scores. RESULTS: There were moderate correlations between the SPSQ score and the overall OSCE score (.45) and the response to patient's emotions skill score (.36). The faculty observer's response to patient's emotion score correlated highly with the student's overall OSCE score (.75). CONCLUSIONS: A student's ability to respond to the patient's emotions appears to be an important skill for successful medical interviewing from both the faculty observer's perspective and the SP's perspective. Results also demonstrate that the SP's perspective is similar, but not identical, to the faculty observer's perspective, suggesting that SPs have an important evaluative role in student assessment.

Emotions↗
PubMed1999

Collagen-bound von Willebrand factor has reduced affinity for factor VIII.

von Willebrand factor (vWf) is a multimeric adhesive glycoprotein that serves as a carrier for factor VIII in plasma. Although each vWf subunit displays a high affinity binding site for factor VIII in vitro, in plasma, only 2% of the vWf sites for factor VIII are occupied. We investigated whether interaction of plasma proteins with vWf or adhesion of vWf to collagen may alter the affinity or availability of factor VIII-binding sites on vWf. When vWf was immobilized on agarose-linked monoclonal antibody, factor VIII bound to vWf with high affinity, and neither the affinity nor binding site availability was influenced by the presence of 50% plasma. Therefore, plasma proteins do not alter the affinity or availability of factor VIII-binding sites. In contrast, when vWf was immobilized on agarose-linked collagen, its affinity for factor VIII was reduced 4-fold, with KD increasing from 0.9 to 3.8 nM. However, one factor VIII-binding site remained available on each vWf subunit. A comparable reduction in affinity for factor VIII was observed when vWf was a constituent of the subendothelial cell matrix and when it was bound to purified type VI collagen. In parallel with the decreased affinity for factor VIII, collagen-bound vWf displayed a 6-fold lower affinity for monoclonal antibody W5-6A, with an epitope composed of residues 78-96 within the factor VIII-binding motif of vWf. We conclude that collagen induces a conformational change within the factor VIII-binding motif of vWf that lowers the affinity for factor VIII.

Animals↗
PubMed1998

Unsaturated phospholipid acyl chains are required to constitute membrane binding sites for factor VIII.

Membranes containing phosphatidyl-L-serine (PS) and phosphatidylethanolamine (PE) greatly enhance the function of the enzymatic cofactor factor VIII. The mechanisms of enhanced function involve condensation of enzyme (factor IXa), activated cofactor (factor VIIIa), and substrate (factor X) at a common location and, most dramatically, activation of the assembled enzyme-cofactor complex. We asked whether unsaturated phospholipid (PL) acyl chains are necessary to constitute factor VIII binding sites or to activate the factor VIIIa-factor IXa complex. We found that membranes composed of saturated, dimyristoyl phospholipids had 20-fold fewer factor VIII binding sites and that these sites supported less than 5% normal activity of the factor VIIIa-factor IXa complex. Thrombin-activated factor VIII bound to a similar number of membrane sites, and thrombin activation did not reduce the affinity for saturated membranes more than 2-fold so that the loss of functional activity is due to a requirement of the factor VIIIa-factor IXa complex for unsaturated acyl chains that exceeds the requirement for factor VIII binding alone. Replacement of dimyristoyl-PS, -PE, or -PC individually with the corresponding unsaturated phospholipid restored 75%, 60%, and 15%, respectively, of factor VIII binding sites but less than 10% of factor VIIIa-factor IXa activating activity. Lyso-PS did not support binding of factor VIII or function of the factor VIIIa-factor IXa complex even when PE and phosphatidylcholine contained unsaturated acyl chains. We conclude that the sn-2 acyl chain of PS and unsaturated phospholipid acyl chains are chemical requirements for constitution of fully functional factor VIII binding sites on phospholipid membranes.

Animals↗
PubMed1998

Binding of factor VIII to von willebrand factor is enabled by cleavage of the von Willebrand factor propeptide and enhanced by formation of disulfide-linked multimers.

von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor VIII binding site/subunit. Prior reports suggest that posttranslational modifications of vWF, including formation of N-terminal intersubunit disulfide bonds and subsequent cleavage of the propeptide, influence availability and/or affinity of factor VIII binding sites. We found that deletion of the vWF propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold lower affinity than multimeric vWF in an equilibrium flow cytometry assay (approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF with the vWF propeptide in trans yielded multimeric vWF that displayed increased affinity for factor VIII. Insertion of an alanine residue at the N-terminus of the mature vWF subunit destroyed binding to factor VIII, indicating that the native mature N-terminus is required for factor VIII binding. The requirement for vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide cleavage site yielding pro-vWF that was defective in factor VIII binding and (2) correlation between efficiency of intracellular propeptide cleavage and factor VIII binding. Furthermore, in a cell-free system, addition of the propeptide-cleaving enzyme PACE/furin enabled factor VIII binding in parallel with propeptide cleavage. Our results indicate that high-affinity factor VIII binding sites are located on N-terminal disulfide-linked vWF subunits from which the propeptide has been cleaved.

Binding Sites↗
PubMed1998

Structure and topography of the membrane-binding C2 domain of factor VIII in the presence of dodecylphosphocholine micelles.

A 21 residue peptide from the C2 domain of the antihaemophilic factor VIII competes with factor VIII for membrane-binding sites in vitro. Here, we provide the structure and topography of the peptide in solution, on dodecylphosphocholine (DPC) micelles, determined using 1H-NMR spectroscopy. The peptide assumes an amphipathic structure comprising an extended N-terminal region and a C-terminal helix. The average root-mean-square deviation is 0.7+/-0.2 A for the superimposition of the backbone atoms of Ile6 to Arg18 on the lowest energy structure. Whereas the backbone conformation is similar to that in SDS micelles, the Trp11 side-chain orientation is dramatically changed. The indole ring is nearly parallel to the peptide backbone in SDS micelles but perpendicular in DPC micelles. Further, pKa values of the two histidines change by more than 1 pH unit in SDS relative to DPC, which localizes the imidazole rings to the interfacial region. Line-broadening induced by spin-labelled phosphatidylcholine shows that most of the amino acid side-chains that penetrate the DPC micelle are hydrophobic. Thus, the long axis of the peptide lies parallel to the micelle surface and the hydrophobic face of the alpha-helix provides hydrophobic membrane interaction. The large chemical shift changes shown by Trp11 and N-terminal amino acid residues in SDS relative to DPC indicate that this region may be involved in membrane phospholipid recognition. 1H-NMR assignments, CD spectra, one-dimensional 1H-NMR spectra, chemical-shift analysis and nuclear Overhauser effect information are reported in Supplementary Publication SUP 50184 (11 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K, from whom copies can be obtained according to the terms indicated in Biochem. J. (1997) 321, 8.

Amino Acid Sequence↗
PubMed1997

Partial activation of the factor VIIIa-factor IXa enzyme complex by dihexanoic phosphatidylserine at submicellar concentrations.

Phosphatidylserine (PS)-containing membranes increase the kcat of the factor VIIIa-factor IXa enzyme complex by more than 1000-fold. While PS supports specific, high-affinity membrane binding of factor VIIIa and factor IXa, it is not known whether PS is the lipid that activates the membrane-bound complex. It is also not known whether PS or other activating lipids must reside in the two-dimensional membrane matrix for efficacy. We have found that submicellar concentrations of dihexanoic phosphatidylserine (C6PS) increase the activity of the factor VIIIa-factor IXa complex in a biphasic manner with half-maximal concentrations of 0.2 and 1.6 mM while the micelle-forming concentration is 4.0 mM. Increased cleavage of factor X at 0.25 mM C6PS was due to a 25-fold enhancement of the kcat and a 30-fold increase in the affinity of factor VIIIa for factor IXa. C6 phosphatidylethanolamine and C6 phosphatidic acid, but not C6 phosphatidylcholine, also accelerated the Xase complex, indicating that kcat enhancement has less structural specificity than membrane binding. Submicellar C6PS enhanced activity of factor IXa in the absence of factor VIIIa, but the effect was due to a decreased KM rather than an increased kcat. These results suggest that activation of the factor VIIIa-factor IXa complex can result from binding of individual C6PS molecules or small aggregates in the absence of a membrane bilayer. They provide a model system in which the phospholipid-induced activation may be distinguished from membrane-binding of the enzyme complex.

Calcium↗
PubMed1996

Slowed release of thrombin-cleaved factor VIII from von Willebrand factor by a monoclonal and a human antibody is a novel mechanism for factor VIII inhibition.

The anti-factor VIII (fVIII) C2 domain monoclonal antibody ESH8 inhibits fVIII activity only when fVIII is bound to von Willebrand factor (vWf). However, ESH8 binds with similar affinity to fVIII and fVIII.vWf complex, and it does not affect the kinetics of thrombin cleavage at positions 372 and 740 within the fVIII heavy chain and at 1689 within the light chain. The latter is required for fVIII release from vWf. We showed that ESH8 reduced the initial rate of thrombin-activated fVIII (fVIIIa) release from vWf by 4.3-fold compared to that in the absence of antibody. The complex of vWf. fVIII.ESH8 was activated, and the rate constant determined for fVIIIa dissociation from vWf was 4 x 10(-3) s-1. We constructed a mathematical model incorporating the measured rates for fVIIIa release from vWf and for inactivation of heterotrimeric fVIIIa due to the spontaneous loss of the A2 subunit and found that the decreased release rate is sufficient to explain our experimentally observed inhibition of fVIII activity by ESH8. We hypothesize that the slowed rate of fVIIIa release from vWf in the presence of ESH8 allows time for inactivation of unstable fVIIIa prior its participation in the formation of the factor Xase complex. The relevance of these findings is illustrated by our observation that reduction of fVIIIa release from vWf represents an additional mechanism of fVIII inhibition by an anti-C2 domain antibody (epitope 2218-2307) from a hemophilia A patient. This rare antibody binds to a more amino-terminal epitope than other human anti-C2 inhibitors, resulting in its lack of inhibition of fVIII binding to vWf but not to phospholipid. These two fVIII ligands therefore bind to C2 sites which do not overlap completely.

Antibodies, Monoclonal↗
PubMed1996

Activation of the factor VIIIa-factor IXa enzyme complex of blood coagulation by membranes containing phosphatidyl-L-serine.

Factor IXa, a serine protease of blood coagulation, functions at least 100,000 times more efficiently when bound to factor VIIIa on a phospholipid membrane than when free in solution. We have utilized the catalytic activity of the factor VIIIa-factor IXa complex to report the effect of phospholipid membranes on binding of factor IXa to factor VIIIa and on enzymatic cleavage of the product. The apparent affinity of factor IXa for factor VIIIa was 10-fold lower in the absence of phospholipid membranes with a KD of 46 nM versus 4.3 nM with phospholipid membranes. The Km for activation of factor X by the factor VIIIa-factor IXa complex was 1700 nM in solution, 70-fold higher than the value of 28 nM when bound to membranes containing phosphatidyl-L-serine, phosphatidylethanolamine, and phosphatidylcholine at a ratio of 4:20:76. The largest effect of phosphatidyl-L-serine-containing membranes on the factor VIIIa-factor IXa complex was the accelerated rate of peptide bond cleavage, with the k(cat) increased by 1,500-fold from 0.022 to 33 min-1. Membranes in which phosphatidyl-L-serine was replaced by phosphatidyl-D-serine, phosphatidic acid, or phosphatidylglycerol were at least 10-fold less effective for enhancing the k(cat). Thus, while membranes containing phosphatidyl-L-serine enhance condensation of the enzyme with its cofactor and substrate, their largest effect is activation of the assembled factor VIIIa-factor IXa enzyme complex.

Animals↗
PubMed1995

Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site.

The finding that human factor VIII (fVIII) inhibitor antibodies with C2 domain epitopes interfere with the binding of fVIII to phosphatidylserine (PS) suggested that this is the mechanism by which they inactivate fVIII. We constructed a recombinant C2 domain polypeptide and demonstrated that it bound to all six human inhibitors with fVIII light chain specificity. Thus, some antibodies within the polyclonal anti-light chain population require only amino acids within C2 for binding. Recombinant C2 also partially or completely neutralized the inhibitor titer of these plasmas, demonstrating that anti-C2 antibodies inhibit fVIII activity. Immunoblotting of a series of C2 deletion polypeptides, expressed in Escherichia coli, with inhibitor plasmas showed that the epitopes for human inhibitors consist of a common core of amino acid residues 2248 through 2312 with differing extensions for individual inhibitors. The epitope of inhibitory monoclonal antibody (MoAb) ESH8 was localized to residues 2248 through 2285. Three human antibodies and anti-C2 MoAb NMC-VIII/5 bound to a synthetic peptide consisting of amino acids 2303 through 2332, a PS-binding site, but MoAb ESH8 did not. These antibodies also inhibited the binding of fVIII to synthetic phospholipid membranes of PS and phosphatidylcholine, confirming that the blocked epitopes contribute to membrane binding as well as binding to PS. In contrast, MoAb ESH8 did not inhibit binding. As the maximal function of activated fVIII in the intrinsic factor Xase complex requires its binding to a phospholipid membrane, we propose that fVIII inhibition by anti-C2 antibodies is related to the overlap of their epitopes with the PS-binding site. MoAb ESH8 did not inhibit fVIII binding to PS-containing membranes, suggesting the existence of a second mechanism of fVIII inhibition by anti-C2 antibodies.

Amino Acid Sequence↗
PubMed1995

Phosphatidylethanolamine induces high affinity binding sites for factor VIII on membranes containing phosphatidyl-L-serine.

Synthetic membranes of phosphatidylcholine require inclusion of at least 5% phosphatidylserine (Ptd-L-Ser) to form binding sites for factor VIII. The relatively high requirement for Ptd-L-Ser suggests that stimulated platelets may contain another membrane constituent that enhances expression of factor VIII-binding sites. We report that phosphatidylethanolamine (PE), which is exposed in concert with Ptd-L-Ser in the course of platelet stimulation, induces high affinity binding sites for factor VIII on synthetic membranes containing 1-15% Ptd-L-Ser. The affinity of factor VIII for binding sites on membranes of Ptd-L-Ser/PE/phosphatidylcholine in a 4:20:76 ratio was 10.2 +/- 3.5 nM with 180 +/- 33 phospholipid molecules/site. PE did not induce binding sites on membranes of 4% Ptd-D-Ser, indicating that the induced binding sites require the correct stereochemistry of Ptd-L-Ser as well as PE. Egg PE and dimyristoyl-PE were equivalent for inducing factor VIII-binding sites, indicating that hexagonal phase-inducing properties of PE are not important. We conclude that PE induces high affinity factor VIII-binding sites on membranes with physiologic mole fractions of Ptd-L-Ser, possibly including those of stimulated platelets.

Binding Sites↗
PubMed1995

Membrane-binding peptide from the C2 domain of factor VIII forms an amphipathic structure as determined by NMR spectroscopy.

Factor VIII binds to cell membranes prior to assembling with the serine protease, factor IXa, to form the factor X-activating enzyme complex. In order to better understand the interaction between factor VIII and phosphatidylserine-containing membranes, we have synthesized the membrane-binding peptide from the C2 domain of factor VIII, corresponding to residues 2303-2324. The peptide, fVIII2303-24, with a primary structure of TRYLRIHPQSWVHQIALRMEVL, aggregates at concentrations above 2 microM at pH 7 but is soluble at pH 6. fVIII2303-24 competes with fluorescein-labeled factor VIII (Ki = 3 microM) for binding sites on synthetic phosphatidylserine-containing membranes and for binding sites on stimulated platelets. Circular dichroism spectra indicate that fVIII2303-24 is predominantly a random coil in aqueous solution but adopts a predominantly helical conformation upon interaction with SDS micelles. 1H NMR spectroscopy in the presence of SDS micelles allowed estimation of interproton distances from the nuclear Overhauser effect and estimation of torsion angles from coupling constants indicated by splitting of resonance lines. The distance and angle estimates, processed by distance geometry/simulated annealing software, indicate that fVIII2303-24 has an alpha-helical segment encompassing residues P8-E20 and an extended segment encompassing residues L4-P8. The location of six hydrophobic residues on one face of the structure suggests that hydrophobic interactions contribute to membrane-binding. In addition, two arginines penetrate the hydrophobic plane suggesting that they interact with phosphate moieties in a phospholipid bilayer.

Amino Acid Sequence↗
PubMed1993

Specific membrane binding of factor VIII is mediated by O-phospho-L-serine, a moiety of phosphatidylserine.

Phosphatidylserine, a negatively charged lipid, is exposed on the platelet membrane following cell stimulation, correlating with the expression of factor VIII receptors. We have explored the importance of the negative electrostatic potential of phosphatidylserine vs chemical moieties of phosphatidylserine for specific membrane binding of factor VIII. Fluorescein-labeled factor VIII bound to membranes containing 15% phosphatidic acid, a negatively charged phospholipid, with low affinity compared to phosphatidylserine-containing membranes. Binding was not specific as it was inhibited by other proteins in plasma. Factor VIII bound to membranes containing 10% phosphatidylserine in spite of a varying net charge provided by 0-15% stearylamine, a positively charged lipid. The soluble phosphatidylserine moiety, O-phospho-L-serine, inhibited factor VIII binding to phosphatidylserine-containing membranes with a Ki of 20 mM, but the stereoisomer, O-phospho-D-serine, was 5-fold less effective. Furthermore, binding of factor VIII to membranes containing synthetic phosphatidyl-D-serine was 5-fold less than binding to membranes containing phosphatidyl-L-serine. Membranes containing synthetic phosphatidyl-L-homoserine, differing from phosphatidylserine by a single methylene, supported high-affinity binding, but it was not specific as factor VIII was displaced by other plasma proteins. O-Phospho-L-serine also inhibited the binding of factor VIII to platelet-derived microparticles with a Ki of 20 mM, and the stereoisomer was 4-fold less effective. These results indicate that membrane binding of factor VIII is mediated by a stereoselective recognition O-phospho-L-serine of phosphatidylserine and that negative electrostatic potential is of lesser importance.

Binding Sites↗
PubMed1993

Membrane binding kinetics of factor VIII indicate a complex binding process.

Factor VIII functions as a component of the tenase enzyme complex upon phospholipid membranes. Factor VIII binds to phosphatidylserine-containing membranes and apparently provides high affinity binding sites for factor IXa upon these membranes. We have characterized the binding kinetics of human factor VIII with phosphatidylserine-containing membranes and directly compared the measured properties with those of factor V. The initial phase of association was evaluated in a stopped-flow apparatus by fluorescence energy transfer from aromatic residues in the protein to dansyl-labeled phosphatidylethanolamine in the vesicles. Association proceeded at an apparent second-order rate of 0.12 microM-1 s-1 for extruded phospholipid vesicles and 0.42 microM-1 s-1 for sonicated vesicles under pseudo-first-order conditions in which the phospholipid concentration determined the rate. Increased temperature resulted in more rapid association, and the effect decreased in the order extruded vesicles > sonicated vesicles > extruded vesicles of dioleoylphospholipids, indicating that the structure of the phospholipid membrane contributes to the activation energy of binding. The binding of fluorescein-labeled factor VIII to membranes supported on glass microspheres (lipospheres) was monitored by flow cytometry. Under conditions in which the factor VIII concentration determined the rate there was rapid initial association at 6.9 microM-1 s-1, accounting for half of the bound factor VIII, and a slower component of 0.87 microM-1 s-1, accounting for the other half. Likewise, the dissociation of factor VIII from liposphere membranes was biphasic with a faster component of 0.010 s-1 and a slower component of 0.0012 s-1. Rates of association and dissociation for factor V were similar to those for factor VIII and were biphasic. These results allow estimation of the size of the phospholipid sites that interact with factors VIII and V and suggest that both proteins bind to membranes via a multistep process in which rapid association is followed by a slower step yielding higher affinity binding.

Animals↗
PubMed1993

Serum lipoprotein(a) levels in elderly black and white men in the Charleston Heart Study.

Lipoprotein(a) [Lp(a)] is an important genetic trait associated with cardiovascular disease. While Lp(a) levels have been demonstrated to be approximately twice as high in black adults and children compared with whites, this relationship has not been assessed in the elderly. During the 1987 recall of the Charleston Heart Study cohort, plasma Lp(a) [mg/dl] was measured on 113 white men and 83 black men. The average age of those having Lp(a) measurements was 71 years (+/- 6) for white men and 72 years (+/- 9) for black men. The distribution of Lp(a) was skewed in both whites (mean = 14.8, median = 8.2 mg/dl) and blacks (mean = 18.1, median = 12.8 mg/dl). The skewed distribution in elderly black men was in contrast to the bell-shaped distribution commonly reported for younger blacks. The Charleston Heart Study data suggest a shift to lower values among elderly as compared to younger men, with the greatest shift occurring among the black men. For black men who have survived to the 7th, 8th, and 9th decades of life, Lp(a) levels appear to be approaching the lower levels of white men. Despite this shift in distribution among black men, there remained a statistically significant difference in Lp(a) between racial groups.

Aged↗
PubMed1993

Electrocardiographic abnormalities and 30-year mortality among white and black men of the Charleston Heart Study.

BACKGROUND: The long-term predictive significance of a single ECG tracing for mortality was explored among the white and black men of the Charleston Heart Study. METHODS AND RESULTS: The 1960 baseline tracings of men ages 35 to 74 in the Charleston Heart Study cohort were coded according to the Minnesota classification. Tracings were categorized as being normal or having minor or major abnormalities. The 30-year vital status was ascertained for the cohort, and the association between ECG findings and coronary and all-cause mortality was evaluated. The proportion of black men with major abnormalities at the 1960 baseline examination was almost twice that of white men. Rates of all-cause mortality increased with severity of abnormalities for white and black men. The absolute excess risk for black men with major abnormalities was 23.3 per 1000 person-years and 12.8 for white men. The excess risk for coronary mortality was 7.3 for white men and 6.5 for black men. CONCLUSIONS: Many of the findings in this study confirm earlier associations derived from studies of white populations and extend the observations to black men. However, the magnitude of the relative risk for mortality was different for white and black men. After controlling for traditional coronary disease risk factors and minor abnormalities, white men with major abnormalities were 2.72 (95% confidence interval, 1.47, 5.04) times more likely to die of coronary disease compared with black men, who were 1.95 (95% confidence interval, 0.93, 4.11) times more likely to die of coronary disease.

Adult↗