ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—HDL molecules have an established role in the regression processes of atherosclerosis as well as a putative role as antiinflammatory agents. Our study investigated whether familial hypoalphalipoproteinemia, a genetic form of dyslipidemia characterized by very low HDL levels, might be associated with increased inflammation markers such as C-reactive protein.Methods and Results—A total of 50 subjects with hypoalphalipoproteinemia (age, 53.1±16.7 years) were compared with 64 healthy controls (age, 51.9±12.4 years). Apart from significantly lower values of HDL cholesterol (30.2±4.0 versus 52.5±12.7 mg/dL,P<0.0001) and apolipoprotein AI (113.3±20.0 versus 155.4±24.9 mg/dL,P<0.0001) and higher levels of triglycerides (141.3±62.9 versus 73.5±39.9 mg/dL,P<0.0001), patients did not show different plasma values of total cholesterol and LDL cholesterol when compared with healthy controls (181.5±36.6 versus 186.3±32.6 mg/dL; 123.0±31.5 versus 119.1±30.3 mg/dL). CRP plasma values were significantly higher in patients than in controls (median 0.34 [range 0.02 to 4.66] versus 0.07 [0.02 to 0.85] mg/dL,P<0.0001). In the patient group, CRP values were significantly higher in subjects with angiographically documented coronary atherosclerotic disease than in those without. Moreover, CRP concentrations were inversely correlated with both HDL cholesterol (r= −0.44,P=0.0006) and apolipoprotein AI (r= −0.45,P=0.0006) values.Conclusions—Elevation of C-reactive protein values in familial hypoalphalipoproteinemia, in the absence of signs and symptoms of local or systemic inflammation or systemic or recurrent disease, may suggest an upregulation of proinflammatory mechanisms, which is further exacerbated by the presence of coronary atherosclerotic disease.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed.Methods and Results—In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus,Hemophilus influenzae,Chlamydia pneumoniae,Mycoplasma pneumoniae, andHelicobacter pyloriwere measured. The extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle-arm index. Elevated IgA antibodies againstC pneumoniae(P<0.04) and IgG antibodies againstH pylori(P<0.02), cytomegalovirus (P<0.05), and herpes simplex virus 2 (P<0.01) were associated with advanced atherosclerosis (≥2 vascular regions), adjusted for age, sex, cardiovascular risk factors, and highly sensitive C-reactive protein. Infectious burden divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities was significantly associated with advanced atherosclerosis, with an odds ratio (95% CI) of 1.8 (1.2 to 2.6) for 4 to 5 (P<0.01) and 2.5 (1.2 to 5.1) for 6 to 8 seropositivities (P<0.02) (adjusted). After a mean follow-up of 3.2 years, cardiovascular mortality rate was 7.0% in patients with advanced atherosclerosis and seropositive for 0 to 3 pathogens compared with 20.0% in those seropositive for 6 to 8 pathogens.Conclusions—Our results support the hypothesis that infectious agents are involved in the development of atherosclerosis. We showed a significant association between infectious burden and the extent of atherosclerosis. Moreover, the risk for future death was increased by the number of infectious pathogens, especially in patients with advanced atherosclerosis.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg/d. High-dose folic acid (5 mg/d) improves endothelial function in CAD, although the mechanism is controversial. It has been proposed that improvement occurs through reduction in total (tHcy) or free (non–protein bound) homocysteine (fHcy). We investigated the effects of folic acid on endothelial function before a change in homocysteine in patients with CAD.Methods and Results—A randomized, placebo-controlled study of folic acid (5 mg/d) for 6 weeks was undertaken in 33 patients. Endothelial function, assessed by flow-mediated dilatation (FMD), was measured before, at 2 and 4 hours after the first dose of folic acid, and after 6 weeks of treatment. Plasma folate increased markedly by 1 hour (200 compared with 25.8 nmol/L;P<0.001). FMD improved at 2 hours (83 compared with 47 &mgr;m;P<0.001) and was largely complete by 4 hours (101 compared with 51 &mgr;m;P<0.001). tHcy did not significantly differ acutely (4-hour tHcy, 9.56 compared with 9.79 &mgr;mol/L;P=NS). fHcy did not differ at 3 hours but was slightly reduced at 4 hours (1.55 compared with 1.78 &mgr;mol/L;P=0.02). FMD improvement did not correlate with reductions in either fHcy or tHcy at any time.Conclusions—These data suggest that folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Left atrial (LA) thrombus is infrequently detected in the presence of sinus rhythm (SR) and, in these cases, is usually associated with additional cardiac pathologies. We sought to determine the clinical and echocardiographic characteristics of patients with LA thrombus and SR to define a high-risk group of patients prone to this uncommon clinical presentation.Methods and Results—The institution’s echocardiographic laboratory database was searched to identify patients with LA thrombus, diagnosed by transesophageal echocardiography (TEE), who were in SR during the TEE examination. Of 20 643 consecutive TEE examinations performed during an 11-year period, LA thrombus was detected in 314 patients in 380 TEE examinations. Of these, SR was present in 20 patients (age 69±13 years; 40% men) in 23 examinations (0.1% of all TEE examinations; 6.1% of TEE examinations with LA thrombus). High-risk structural heart disease (severe left ventricular dysfunction or significant left-sided valve disease [predominantly mitral valve disease]), previous documented episodes of atrial fibrillation, or both (structural heart disease and previous atrial fibrillation) were present in 10, 4, and 5 of the 20 patients, respectively. Only 1 patient with LA thrombus and SR did not have high-risk features.Conclusions—LA thrombus is very infrequently detected in the presence of SR. Patients with LA thrombus and SR constitute a high-risk group characterized by specific structural cardiac abnormalities or previous atrial fibrillation, abnormalities that are potentially detectable before TEE.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—Coronary artery disease can develop prematurely and is the leading cause of death among diabetics, making noninvasive risk stratification desirable.Methods and Results—Patients with symptoms of coronary artery disease who were undergoing stress myocardial perfusion imaging (MPI) from 5 centers were prospectively followed (2.5±1.5 years) for the subsequent occurrence of cardiac death, myocardial infarction (MI), and revascularization. Stress MPI results were categorized as normal or abnormal (fixed or ischemic defects and 1, 2, or 3 vessel distribution). Of 4755 patients, 929 (19.5%) were diabetic. Patients with diabetes, despite an increased revascularization rate, had 80 cardiac events (8.6%; 39 deaths and 41 MIs) compared with 172 cardiac events (4.5%; 69 deaths and 103 MIs) in the nondiabetic cohort (P<0.0001). Abnormal stress MPI was an independent predictor of cardiac death and MI in both populations. Diabetics with ischemic defects had an increased number of cardiac events (P<0.001), with the highest MI rates (17.1%) observed with 3-vessel ischemia. Similarly, a multivessel fixed defect was associated with the highest rate of cardiac death (13.6%) among diabetics. The unadjusted cardiac survival rate was lower for diabetic patients (91% versus 97%,P<0.001), but it became comparable once adjusted for the pretest clinical risk and stress MPI results. In multivariable Cox analysis, both ischemic and fixed MPI defects independently predicted cardiac death alone or cardiac death/MI. Diabetic women had the worst outcome for any given extent of myocardial ischemia.Conclusions—In this large cohort of diabetics undergoing stress MPI, the presence and the extent of abnormal stress MPI independently predicted subsequent cardiac events. Using stress MPI in conjunction with clinical information can provide risk stratification of diabetic patients.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background—The SA gene (SAH) has been isolated by differential screening from a genetically hypertensive rat strain as a candidate gene that may contribute to hypertension. Recently, the SA protein has been reported to be highly homologous to bovine xenobiotic–metabolizing medium-chain fatty acid:CoA ligase.Methods and Results—To clarify the pathophysiological significance ofSAH, we searched for polymorphisms of humanSAHand performed association studies using a large cohort (4000 subjects) representing the general population in Japan. We found 2 polymorphisms in the promoter region and single-nucleotide polymorphisms in introns 5, 7, and 12 and exon 8. One of the variants, an A/G polymorphism in intron 12, just 7 bp upstream from exon 13, strongly affected plasma triglyceride, plasma cholesterol, body mass index (BMI), waist-to-hip ratio (W/H), and blood pressure status. The effect of this genotype on blood pressure seems to be conveyed through its effects on BMI and W/H. Transient expression of the SA protein in mammalian cells confirmed that it is expressed in mitochondria and has medium-chain fatty acid:CoA ligase activity. The A/G polymorphism was found to be associated with the expression level of SA mRNA in peripheral mononuclear cells in vivo.Conclusions—The G allele ofSAHwas found to be associated with multiple risk factors, including hypertriglyceridemia, hypercholesterolemia, obesity, and hypertension. This observation should open a new area for future research in multiple-risk-factor syndromes.

ISSN:0009-7322    

出版商:OVID    

年代:2002

数据来源: OVID