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Biomedical subjects

C Schmitz

Publications and source records attributed to C Schmitz.

At least 91 records · Page 5Linked to original sources
PubMed1999

Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study.

The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the PlA2 polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR-based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and ADP were determined. Allele frequencies of PlA1 and PlA2 were 0.84 and 0.16, respectively. The presence of 1 or 2 PlA2 alleles was associated with increased platelet aggregability as indicated by incrementally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 micromol/L (0.9 to 1.0) for homozygous PlA1, 0.7 mmol/L (0.7 to 0.9) for the heterozygous PlA1/PlA2, and 0.6 micromol/L (0.4 to 1.0) for homozygous PlA2 individuals, P=0.009. The increase in aggregability induced by epinephrine remained highly significant (P=0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 micromol/L (3.0 to 3.2), 3.0 micromol/L (2.9 to 3.2), and 2.8 micromol/L (2.4 to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GP IIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the PlA2 allotype with increased risk for cardiovascular disease.

Adenosine Diphosphate↗
PubMed1999

Hypertension-induced end-organ damage : A new transgenic approach to an old problem.

Angiotensin (Ang) II-induced organ damage has fascinated students of hypertension since the work of Wilson and Byrom. We are investigating a double transgenic rat (dTGR) model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1) are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, and VEGF expression. The expression of TGF-beta and deposition of extracellular matrix proteins follows, which is accompanied by fibrinoid vasculitis in small vessels of the heart and kidneys. Angiotensin-converting enzyme inhibitors and AT1 receptor blockers each lowered blood pressure and shifted pressure natriuresis partially leftward by different mechanisms. When combined, they normalized blood pressure, pressure natriuresis, and protected from vasculopathy completely. Renin inhibition lowered blood pressure partially, but protected from vasculopathy completely. Endothelin receptor blockade had no influence on blood pressure but protected from vasculopathy and improved survival. We show evidence that Ang II stimulates oxidative stress directly or indirectly via endothelin 1 and that NFkappaB is upregulated in this model. We speculate that the transcription factors NFkappaB and AP-1 are involved with initiating chemokine and cytokine expression, leading to the above cascade. The unique model and our pharmacological probes will enable us to test these hypotheses.

Angiotensin II↗
PubMed1998

Disruption of endothelial microfilaments selectively reduces the transendothelial migration of monocytes.

The transendothelial migration of leukocytes (diapedesis) is a central event in inflammatory and immunological processes. Although leukocyte-endothelium interactions occurring during diapedesis have been investigated intensively, little is known about the actual transmigration and the molecular mechanisms involved. Toward this end we analyzed whether the endothelial cytoskeleton plays a direct role during the transendothelial migration of monocytes. Filter-grown monolayers of human microvascular endothelial cells (HMEC-1) were treated with cytoskeleton stabilizing or destabilizing drugs and the effect of this treatment on the transmigration of peripheral blood monocytes was analyzed in a two-chamber assay. Our results show that taxol-induced stabilization of microtubules causes a reduction of leukocyte transmigration through HMEC-1, while the opposite effect is induced by the destabilization of microtubules with colchicine or nocodazol. Disruption of microfilaments with cytochalasin B or latrunculin A, on the other hand, significantly reduces the transendothelial migration although monocyte adhesion and endothelial permeability for macromolecules are slightly increased. An active participation of the endothelial microfilament system with a direct role of unconventional, calmodulin-regulated myosins is suggested by the finding that monocyte transmigration is decreased upon treatment of the endothelial cells with the Ca2+/CaM antagonist triflouperazine.

Actin Cytoskeleton↗
PubMed1998

Angiotensinogen gene and hypertension in Chinese.

The renin-angiotensin system plays a major role in regulating blood pressure and maintaining electrolyte and volume homeostasis. Previously, the angiotensinogen gene, which encodes the key substrate for renin within this system, has been reported linked to and associated with essential hypertension in White Europeans, African-Caribbeans, and Japanese. Therefore, we investigated whether the angiotensinogen gene might be similarly implicated in the pathogenesis of essential hypertension in Chinese by carrying out linkage analysis in 310 hypertensive sibling pairs. Genotypes for two diallelic DNA polymorphisms observed at amino acid residues 174 (T174M) and 235 (M235T) within the coding sequence and for two highly informative dinucleotide (GT)-repeat sequences (one in the 3' flanking region, and one at a distance of 6.1 cM from the gene) were determined. Affected sibpair analysis conducted according to three different algorithms (S.A.G.E./SIBPAL, MAPMAKER/ SIBS, and APM methods) revealed no evidence for linkage of the angiotensinogen gene to hypertension. Our data indicate that molecular variants of this gene do not appear to contribute materially to the pathogenesis of primary hypertension among Chinese (a notion supported by concomitant, direct estimates of power), and that the disease relevance of this gene may vary therefore depending on ethnicity.

Alleles↗
PubMed1998

Variation of fractionator estimates and its prediction.

Over the last decade the so-called 'fractionator' has become widespread in anatomical and pathological research for obtaining unbiased estimates of total numbers of particles in biological specimens. Several methods have been proposed for predicting the precision (i.e., the variation) of the estimated total numbers of particles using the fractionator (i.e., for predicting the precision of fractionator estimates). However, the validity of these predicting methods has not been tested so far. As it is impossible to do so with biological experiments, it was carried out here by using a computer simulation. Specimens containing particles, with various particle distributional patterns, were modeled, and the total number of particles in the specimens was estimated repeatedly with various modeled sampling schemes. It could be shown that the empirically estimated precision of the modeled fractionator estimates depend on both the particle distributional pattern in a modeled specimen as well as on the applied sampling scheme. Furthermore, considerable differences between the predicted and the empirically estimated precision of the modeled fractionator estimates were found. This was due partly to an incorrect assumption, which serves as the basis for one of the proposed predicting methods, partly to the fact that for some of the proposed predicting methods important contributions to the variation of fractionator estimates have not been considered, and partly to the fact that the mathematical theory, which serves as the basis for all predicting methods proposed so far, can in principle not be the optimum basis for predicting the precision of fractionator estimates. Based on the results of the computer simulation, a new, simple method is proposed for predicting the precision of fractionator estimates.

Cell Count↗
PubMed1998

Minimally invasive coronary artery bypass grafting: port-access approach versus off-pump techniques.

BACKGROUND: Within the past 5 years several surgical techniques have been developed for less invasive surgical treatment of coronary artery disease. The aim of this study was to define specific indications for the various minimally invasive coronary artery surgical procedures. METHODS: Minimally invasive direct coronary artery bypass grafting through a minithoracotomy was performed in 67 patients. The left internal mammary artery was anastomosed on the beating heart with the use of a pressure or suction stabilizer without the use of extracorporeal circulation. In 58 other patients with multivessel disease, the off-pump coronary artery bypass grafting technique through a sternotomy was applied with a left internal mammary artery to left anterior descending artery and additional vein grafts without extracorporeal circulation. In a third group, Port-Access (Heartport Inc, Redwood City, CA) coronary artery bypass grafting was performed through a left minithoracotomy with the use of an endovascular extracorporeal circulation system and cardioplegic arrest. Angiographic follow-up was complete in 64% of the patients. RESULTS: There was minimal perioperative or postoperative mortality (0.5%). The medium surgical procedure time for all minimally invasive and off-pump procedures was 2.5 hours; it was 4.5 hours for Port-Access procedures. The median postoperative intensive care unit stay was 1.0 days, and the median hospitalization was 5.0 days. Overall graft patency was 97.3%; in 8 patients (4.1%) a stenosis either at or distal to the graft anastomosis was dilated with coronary angioplasty. CONCLUSIONS: For single-vessel disease of the left anterior descending artery, the minimally invasive coronary artery bypass grafting procedure can be performed safely without the use of extracorporeal circulation. In case of hemodynamic instability or anatomic variation, the Port-Access procedure can be applied without additional necessity for sternotomy. For multivessel disease, the off-pump bypass grafting procedure with sternotomy can be recommended depending on the coronary arteries involved. In case of necessary grafts to the lateral marginal or circumflex branches, Port-Access grafting can be recommended and may play an important role in the future for the development of fully endoscopic robot-assisted coronary artery bypass grafting.

Adult↗
PubMed1998

Pharmacologic heart rate reduction: effect of a novel, specific bradycardic agent on the heart.

Because heart rate (HR) is a major determinant of myocardial oxygen consumption (MVO2) a decrease in HR could prevent ischemia or reduce its consequences. We examined the effects of a novel bradycardic agent of the benzazepinone type, DK-AH 269 (DK), on ventricular function and perfusion in 12 isolated, blood-perfused rabbit hearts. HR was significantly reduced by 1mumol/L DK (160 +/- 28 vs. 124 +/- 23 min-1); diastole lengthened from 235 +/- 69 to 334 +/- 85 ms. Aortic flow tended to fall after DK (50.0 +/- 29.6 vs. 35.6 +/- 21.5 ml/min), but stroke volume remained unchanged (0.29 +/- 0.16 vs. 0.28 +/- 0.17 ml) following DK. Peak left-ventricular pressure (LVPmax) (106 +/- 29 vs. 92 +/- 35 mmHg) and dp/dtmax (1482 +/- 582 vs. 1247 +/- 644 mmHg/s) were decreased. dp/dtmin, as a measure of early relaxation, was also decreased (-1361 +/- 362 vs, -1125 +/- 488 mmHg/s), whereas the end-diastolic pressure (LVPed) was increased (20 +/- 12 vs. 25 +/- 17 mmHg). Coronary blood flow (CBF) per beat was not affected by DK: 0.07 +/- 0.02 vs. 0.07 +/- 0.02 ml. However, the coronary resistance increased with DK from 0.76 +/- 0.29 to 1.13 +/- 0.66 mmHg/(ml/min/100 g). The MVO2 was decreased (6.8 +/- 3.4 vs. 5.9 +/- 2.8 ml/min/100 g). The relation between subendocardial and subepicardial flow (colored microspheres) was unchanged after DK (1.12 +/- 0.22 vs. 1.13 +/- 0.16). Using electrical pacing to restore the control HR, dp/dtmax, LVPed, and MVO2 were nearly restored to predrug levels. In contrast, stroke volume, LVPmax, dp/dtmin and CBF per beat were less than control. In summary: DK effectively reduces heart rate and increases diastole. In parallel with the moderately reduced contractile function, MVO2 is reduced whereas CBF per beat is preserved. These results suggest that this novel bradycardic agent could be useful in treating unwanted tachycardia in the experimental setting, postoperative tachycardia in patients with heart disease or be useful even in treating coronary heart disease.

Animals↗
PubMed1998

Procalcitonin as a marker of systemic inflammation after conventional or minimally invasive coronary artery bypass grafting.

Cardiac surgery using cardiopulmonary bypass (CPB) often induces a systemic inflammatory response syndrome (SIRS). The concept of minimally invasive direct coronary artery bypass (MIDCAB) eliminates cardiopulmonary bypass. We evaluated the perioperative time course of procalcitonin (PCT) to compare the inflammatory response due to these two different surgical procedures. 57 patients were studied: CABG with CPB (n = 30), MIDCAB without CPB (n = 27). The following data were measured preoperatively, after induction of anesthesia, after separation from CPB in the CABG group or after left internal mammary artery (LIMA)-to-left anterior descending artery (LAD) anastomosis in MIDCAB group, and every 3 hours for the first 42 hours in the ICU: PCT, C-reactive protein (CRP), body temperature, hemodynamic parameters, and the need for catecholamines. Leucocyte counts were measured daily. For statistical analyses the Friedmann, Wilcoxon, or Mann-Whitney U tests were used. PCT in the CABG group rose to a maximum of 2.0 ng/ml (median) at 15 hrs postoperatively. In the MIDCAB group maximal PCT concentration was 0.7ng/ml (median) (p < 0.05). CRP was elevated to 17.1 mg/dl in the CABG and 18.5mg/dl in the MIDCAB group (n.s.). The leucocyte counts were increased on day 2 in the CABG group (p < 0.05). In the CABG group about 25% of the patients needed noradrenaline, but in the MIDCAB group none (p < 0.05). Body temperature did not differ between both groups. The increase in PCT concentration was more pronounced after CABG, indicating a reduced inflammatory response after MIDCAB. CRP was increased after both procedures. PCT reflects the inflammatory response after cardiac bypass surgery with or without CPB.

Aged↗
PubMed1998

Continuous, less invasive, hemodynamic monitoring in intensive care after cardiac surgery.

A pulse-contour-based method for continuous measurement of cardiac output (CO) and systemic vascular resistance (SVR) was tested and arterial thermodilution, used for calibration, was compared to pulmonary artery thermodilution. In 30 patients CO and SVR were measured by pulse contour analysis (COpc, SVRpc) 270 times in 24 h and compared to arterial (COart, SVRart) and pulmonary arterial (COpa, SVRpa) thermodilution measurements. The mean difference between COpa and COart was 0.26 L/min (3.6%) with a standard deviation (SD) of 0.7 L/min, the correlation coefficient was 0.96, and the coefficient of variation was 5.0% and 5.9% respectively. COpc did differ from COpa by 0.11 L/min (1.5%, SD = 0.6 L/min) and from COart by 0.15 L/min (2.1%, SD = 0.7 L/min). Correlation of COpc with COpa was 0.91, correlation of COpc with COart was 0.90. SVRpc did correlate with SVRpa, a coefficient of 0.94, and with SVRart, a coefficient of 0.92. Mean COpc and SVRpc did not differ significantly from COpa or COart and SVRpa or SVRart during the 24 h study period. It is concluded that COart correlates well with COpa and can be used to calibrate COpc. COpc and SVRpc agree with thermodilution-based CO and SVR without recalibration for 24 hours.

Adult↗
PubMed1998

High sensitivity of Deinococcus radiodurans to photodynamically-produced singlet oxygen.

PURPOSE: To study the sensitivity of two bacterial cell systems to photodynamic treatment and X-ray irradiation as part of a project to establish efficient procedures for waste water disinfection. MATERIALS AND METHODS: Stationary-phase cells of Deinococcus radiodurans (Gram-positive) and Escherichia coli (Gram-negative) were exposed to visible light in a buffer solution containing up to 5 microg/ml sensitizer rose bengal (RB) and to X-rays at dose rates of 32.8 Gy/min or 14.6 Gy/min, respectively. RESULTS: Survival of both cell types decreased with increasing exposure time to visible light and increasing concentration of RB, and therefore with an increase in singlet oxygen production. Surprisingly, D. radiodurans, the most resistant cell system to ionizing radiation, was more sensitive to photodynamic treatment than E. coli by about a factor of 100. CONCLUSIONS: The main target of singlet oxygen reaction is the cell membrane. The repair of such damage in D. radiodurans is less effective than in E. coli.

Animals↗
PubMed1998

Is cardiac surgery justified in patients in the ninth decade of life?

BACKGROUND: Due to aging of the population the upper-age limit for cardiac operations has constantly been extended. In the current era of health care reform the ability to provide appropriate care for geriatric patients at acceptable costs is a major individual and societal concern. The objective of this study was to evaluate the results of cardiac surgery in octogenarians regarding overall morbidity and mortality as well as to quality of life. METHODS: Between February 1992 and August 1995, 101 consecutive octogenarians underwent several types of cardiac operations. Operative procedures consisted of coronary artery bypass grafting (CABG) in 45 patients, valve replacement or repair in 33 patients, and combined CABG and combined procedures in 19 patients. All surviving patients were mailed a questionnaire 3 to 62 months (22.1+/-15.4 months) postoperatively concerning the postoperative course and quality of life (97.5% follow-up). RESULTS: The early mortality was 15.5% in the CABG group, 3.0% in the valve group, and 21.7% in the combined procedure group; 5-year actuarial survival was 79.1% in the CABG group, 86.9% in the valve group, and 58.8% in the combined procedure group, respectively. The questionnaire sent to the survivors revealed that 81.0% of patients considered their functional status better or much better than before surgery. Of the survivors, 97.3% stated that according to their opinion the operation was worthwhile. CONCLUSION: Cardiac surgery is justified for carefully selected patients in the ninth decade of life. Although these patients are at increased risk of operative death and surgical complications compared with younger patients, the majority regain a life expectancy in the range of that of the global population. Furthermore, they are presented the chance to retain or maintain an independent lifestyle.

Aged↗
PubMed1998

Mitochondrial DNA synthesis studied autoradiographically in various cell types in vivo.

It is generally accepted that mitochondria are able to proliferate even in postmitotic cells due to their natural turnover and also to satisfy increased cell energy requirements. However, no detailed studies are available, particularly with respect to specific cell types. Since [3H]-thymidine is incorporated not only into nuclear (n) DNA but also into the DNA of cytoplasmic mitochondria, an autoradiographic approach was developed at the light microscopy level in order to study basic questions of mitochondrial (mt) proliferation in organs of rodents in situ via the cytoplasmic incorporation of [3H]-thymidine injected into the animals 1 h before sacrifice. Experiments carried out on mice after X-irradiation showed that cytoplasmic labeling was not due to a process such as unscheduled nuclear DNA synthesis (nUDS). Furthermore, half-lives of mitochondria between 8-23 days were deduced specifically in relation to cell types. The phase of mtDNA synthesis was about 75 min. Finally, mt proliferation was measured in brain cells of mice as a function of age. While all neurons showed a decreasing extent of mtDNA synthesis during old age, nUDS decreased only in distinct cell types of the cortex and hippocampus. We conclude that the leading theories explaining the phenomenon of aging are closely related, i.e., aging is due to a decreasing capacity of nDNA repair, which leads to unrepaired nDNA damage, or to an accumulation of mitochondria with damaged mtDNA, which leads to a deficit of cellular energy production.

Aging↗
PubMed1998

Preoperative 3D-reconstructions of ultrafast-CT images for the planning of minimally invasive direct coronary artery bypass operation (MIDCAB).

BACKGROUND: The direct left internal mammary artery (LIMA) bypass to the left anterior descending (LAD) without the use of extracorporal circulation through a small anterolateral thoracotomy has become established among the minimally invasive techniques in cardiac surgery. Technical difficulties may occur in patients with an enlarged left ventricle and subsequent lateral positioning of the LAD, a small LAD, or a small LIMA. We used electron beam tomography (EBT) for preoperative visualization of the topographical structures to seek out patients with potential technical difficulties. METHODS: Eighteen patients, mean age 62 +/- 13 years, were entered in this study; in all cases the indication for revascularization was a significant stenosis of the LAD. Preoperatively an ECG-triggered EBT was performed. Following the image acquisition, a three-dimensional reconstruction of the data was performed. The LIMA, LAD, first diagonal branch, and chest wall were stained different colors for better visualization. Surgery was performed using a left anterolateral mini-thoracotomy and through this access, the LIMA was dissected and anastomosed using a stabilizer without the use of extracorporal circulation. RESULTS: In all but one of the 18 patients who had a preoperative EBT, the minimally invasive direct coronary artery bypass (MIDCAB) procedure was successfully performed using an anterolateral mini-thoracotomy. Based on the results of the EBT, the 5 centimeter incision was done parasternally in six patients, and more laterally (2-4 cm parasternally) in the other eleven cases. In 13 patients the access penetrated the fourth intercostal space; in four cases the fifth intercostal space was used. In one patient EBT revealed a very laterally positioned and diffusely arteriosclerotic LAD so the patient was operated using a median sternotomy, but without the use of extracorporal circulation. In all 18 patients the preoperatively acquired information of the anatomical topography was confirmed intraoperatively. One case without a preoperative EBT had to be converted to a conventional procedure due to a small, intramyocardial LAD and a very small LIMA. Postoperative angiography revealed patent LIMA grafts and uneventful anastomoses. CONCLUSIONS: For minimally invasive direct coronary artery bypass (MIDCAB) the topography of the LIMA, LAD and intercostal spaces is of major importance. Using the ECG-triggered EBT with subsequent three-dimensional reconstruction these relationships can be visualized. This enables an individual planning of the operation and a minimalization of the skin incision.

Aged↗
PubMed1997

Disturbed intracoronary hemodynamics in myocardial bridging: early normalization by intracoronary stent placement.

BACKGROUND: The purpose of this study was to evaluate the hemodynamic mechanisms leading to myocardial ischemia in patients with myocardial bridging. Myocardial bridging is known to induce angina and even severe myocardial ischemia. METHODS AND RESULTS: In 12 symptomatic patients with myocardial bridges, quantitative coronary angiography was performed to obtain systolic/diastolic vessel diameters within the bridged segments. Coronary flow velocities, flow reserve, and pressures were determined with a 0.014-in Doppler and a 0.014-in pressure microtransducer. In 3 symptomatic patients, coronary stents were implanted and hemodynamic measurements were repeated immediately and after 7 weeks. An in vitro validation of the pressure measurements was performed. Angiography revealed a systolic diameter reduction of 80.6+/-9.2% and a persistent diastolic reduction of 35.3+/-11% within the bridged segment. Diastolic flow velocities (cm/s) were increased (31.5+/-14.3 within versus 17.3+/-5.7 proximal and 15.2+/-6.3 distal, P<.001). Coronary flow reserve distal to the bridge was 2.5+/-0.5. There was an increased peak systolic pressure within the bridged segment (171+/-48 versus 113+/-10 mm Hg proximal, P<.001). Stent placement abolished the phasic lumen compression, the diastolic flow abnormalities, the intracoronary peak systolic pressure, and clinical symptoms. Coronary flow reserve improved to 3.8+/-0.3. CONCLUSIONS: Coronary hemodynamics in myocardial bridges are characterized by a phasic systolic vessel compression with a localized peak pressure, persistent diastolic diameter reduction, increased blood flow velocities, retrograde flow, and a reduced flow reserve. These alterations may explain the occurrence of symptoms and ischemia in these patients. Intracoronary stent placement abolished all hemodynamic abnormalities and may improve clinical symptoms in otherwise unsuccessfully treated patients with myocardial bridges.

Adult↗
PubMed1997

PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis.

BACKGROUND: The gene encoding the platelet glycoprotein IIIa receptor (GPIIIa), shows polymorphism (PIA1/A2). In a previous study, men with acute coronary ischaemia were more likely than controls to carry the PIA2 allele. This receptor has an important role in acute thrombus formation; these findings therefore raise the possibility of inherited platelet risk factors for both arterial and venous thrombosis. We investigated whether the PIA2 allele is associated with myocardial infarction, stroke, and venous thrombosis in a large prospective cohort of men in the USA. METHODS: 14916 initially healthy men participating in the Physicians Health Study provided baseline blood specimens for DNA analysis and were followed prospectively for a mean of 8.6 years. 374 men had a first myocardial infarction, 209 stroke, and 121 venous thrombosis during follow-up (704 cases). Distribution of the PIA1/A2 polymorphism was investigated by a PCR based on restriction-fragment length polymorphism in these men and in a sample of 704 matched study participants who remained free of thrombosis during follow-up (controls). FINDINGS: The frequency of the PIA2 allele was similar to the control frequency (14.8%) among men who had myocardial infarction (13.5%, p = 0.4), stroke (13.4%, p = 0.5), or venous thrombosis (14.5%, p = 0.9). The relative risk of any vascular event among men homozygous or heterozygous for PIA2 compared with men homozygous for PIA1 was 0.96 (95% CI 0.8-1.2). We found no evidence of association between the PIA2 allele and myocardial infarction (relative risk 0.93 [95 0.7-1.2]), stroke (0.93 [0.7-1.3]), or venous thrombosis (1.07 [0.7-1.6]). There was no evidence of association in subgroup analyses by age, smoking status, and presence of family history of premature coronary disease, hypercholesterolaemia, hypertension, or diabetes. Aspirin use had no effect on these findings. INTERPRETATION: In a large cohort of apparently healthy men, carriage of the GPIIIa PIA2 allele was not associated with any increase in subsequent risk of myocardial infarction, stroke, or venous thrombosis.

Adult↗