Ascending aortic blood pressure-derived indices are not correlated with the extent of coronary artery disease in patients with impaired left ventricular function

BACKGROUND: Ascending aortic blood pressure-derived indices were shown to be related to coronary atherosclerosis. Unfortunately, most studies published so far included patients with preserved left ventricular function. Therefore, the aim of the present study was to investigate the relation between ascending aortic blood pressure-derived indices and the extent of coronary atherosclerosis in patients with impaired left ventricular function. METHODS: The study group consisted of 375 patients (302 men and 73 women; mean age: 59.0+/-10.1 years) with angiographically confirmed coronary artery disease and ejection fraction < or =55%. Invasive ascending aortic blood pressure during catheterization and conventional sphygmomanometer measurements were taken. RESULTS: None of the brachial or aortic blood pressure-derived indices differed between patients with one-, two- and three-vessel coronary artery disease. They were not independently related to the risk of having three-vessel coronary artery disease in none of the constructed models in logistic regression analysis. Moreover, none of the studied indices was correlated with Gensini or severity scores. We also did not find any significant correlation between blood pressure-derived indices and extent of coronary atherosclerosis in patients with ejection fraction < or =25%, 25-40% or >40%. CONCLUSION: Ascending aortic blood pressure-derived indices are not correlated with the severity of coronary atherosclerosis in patients with coronary artery disease and impaired left ventricular function.     

Ascending aortic blood pressure waveform may be related to the risk of coronary artery disease in women, but not in men

Recent studies have demonstrated that fractional pulse pressure and fractional diastolic pressure are related to the risk of coronary artery disease. However, the effect of the ascending aortic pressure waveform on the risk of coronary artery disease in men and women analyzed separately has not been reported. The objective of the study was to assess the relation between ascending aortic blood pressure waveform and the presence of coronary artery disease in men and in women. The study group consisted of 447 patients (302 men and 145 women; mean age: 57.6+/-9.8 years) with preserved left ventricular function who were undergoing first diagnostic coronary angiography. After multivariate stepwise adjustments, the odds ratio (OR) and confidence interval (CI) of having coronary artery disease in women was (OR are reported for standard deviation increase in each variable): pulse pressure OR 1.61 (95% CI 1.06-2.46); fractional systolic pressure OR 1.72 (95% CI 1.08-2.71); fractional diastolic pressure OR 0.58 (95% CI 0.37-0.92); fractional pulse pressure OR 1.72 (95% CI 1.08-2.71); and pulsatility index OR 1.74 (95% CI 1.09-2.78). None of the studied variables was independently related to the presence of coronary artery disease in men. In conclusion, fractional systolic and diastolic pressure, pulse pressure, fractional pulse pressure and the ratio of pulse pressure to diastolic pressure may be independently related to the risk of coronary artery disease in women, but not in men.     

Ascending aortic blood pressure waveform is related to coronary atherosclerosis in hypertensive as well as in normotensive subjects

Ascending aortic blood pressure-derived indices were shown to be related to coronary atherosclerosis. However, no study so far has analyzed the relation between ascending aortic pulsatility and the extent of coronary atherosclerosis in normotensives. Therefore, the aim of the present analysis was to assess the relation between central blood pressure-derived indices and the presence and extent of coronary artery disease in patients with and without hypertension. The study group consisted of 821 patients (590 men and 231 women; mean age: 57.3 +/- 10.0 years) with preserved left ventricular function (ejection fraction>50%) undergoing coronary angiography. Hypertension was diagnosed in 639 (77.8%) patients. Ascending aortic blood pressure during catheterization was measured. After multivariate stepwise adjustment the odds ratio (OR) and confidence interval (CI) of coronary artery disease was: pulsatility per standard deviation (SD) OR 1.36 (95% CI 1.01-1.82) in hypertensives and OR 3.96 (1.95-8.07) in normotensives; pulsatility index per SD OR 1.36 (95% CI 1.01-1.85) in hypertensives and OR 4.41 (2.03-9.56) in normotensives. Stepwise linear regression analysis revealed that pulsatility is related to the mean stenosis in the coronary tree in hypertensives (beta = 0.0862, SE = 0.0448, p<0.05) as well as in normotensives (beta = 0.1704, SE = 0.0718, p<0.05). In conclusion, ascending aortic pulsatility is related to the extent of coronary atherosclerosis irrespectively of the presence of hypertension.     

Morphologic rather than functional or mechanical sonographic parameters of the brachial artery are related to angiographically evident coronary atherosclerosis

OBJECTIVES: The purpose of this study was to determine the relationship among coronary atherosclerosis and functional, morphologic, and mechanical parameters assessed noninvasively within the brachial artery (BA). BACKGROUND: Flow-mediated vasodilation (FMD) of the BA, intima-media thickness (IMT) of the carotid artery, and distensibility of the aorta have been correlated with the presence of coronary artery disease (CAD). METHODS: The BA was examined with high-resolution ultrasound (13 MHz) in 117 male patients, in whom coronary angiography was performed. Coronary artery disease (> or =30% diameter stenosis in > or =1 major branch) was found in 84 patients, and 33 patients had smooth coronary arteries (non-CAD). Wall cross-sectional area (WCSA) was calculated from resting diameter and IMT. RESULTS: The BA-WCSA (5.3 +/- 1.5 mm(2) vs. 4.4 +/- 1.4 mm(2), p = 0.002) and IMT (0.37 +/- 0.07 mm vs. 0.31 +/- 0.07 mm, p < 0.001) were significantly greater in patients with CAD compared with non-CAD patients. Flow-mediated vasodilation and distensibility were similar among groups. Using logistic regression analyses adjusting for age, positive family history, hypertension, hypercholesterolemia, smoking, FMD, and distensibility, only WCSA (p < 0.01) and IMT (p < 0.001) correlated independently with the presence of CAD. CONCLUSIONS: Morphologic but not functional and mechanical parameters of the BA are associated with the presence of CAD. Among BA sonographic parameters, IMT and WCSA seem to be the most accurate ones for the estimation of coronary atherosclerotic risk.     

颈动脉和股动脉斑块及主动脉弓钙化与冠心病相关

目的 研究颈动脉和股动脉斑块及主动脉弓钙化与冠心病的关系.方法 病人121例,经桡动脉行冠状动脉造影,据造影结果分为正常冠状动脉组及冠心病组,冠心病组又分为1支病变组、2支病变组及3支病变组,分别予体表超声及X胸片检查颈动脉和股动脉斑块及主动脉弓钙化.结果 颈动脉和股动脉斑块及主动脉弓钙化是预测冠心病的有效指标,随斑块及主动脉弓钙化的发生,病变血管数增加.三者相比,颈动脉斑块预测冠心病的敏感性最高,股动脉斑块预测冠心病的特异性最高,而主动脉弓钙化往往与多支病变有关.当三者共存时,冠心病的发生率高达94.8%.结论 颈、股动脉斑块及主动脉弓钙化对冠心病有一定的预测价值.     

Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation, but not to resistance to antihypertensive drug therapy

OBJECTIVES: Most hypertensive patients require two or more drugs to control arterial blood pressure effectively. Although endothelial nitric oxide synthase (eNOS) haplotypes have been associated with hypertension, it is unknown whether eNOS genotypes/haplotypes are associated with resistance to antihypertensive therapy. METHODS: We studied the distribution of three eNOS genetic polymorphisms: single nucleotide polymorphisms in the promoter region (T(-786)C), and in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (b/a). Genotypes were determined for 111 normotensive controls (NT), 116 hypertensive individuals who were well controlled (HT), and 100 hypertensive individuals who were resistant to conventional antihypertensive therapy (RHT). We also compared the distribution of eNOS haplotypes in the three groups of subjects. RESULTS: No differences were found in genotype or allele distribution among the three groups (all P > 0.05). Conversely, the 'C Glu b' haplotype was more commonly found in the NT than in the HT or RHT groups (21 versus 8 and 7%, respectively; both P < 0.00625). In addition, the 'C Asp b' haplotype was more commonly found in the HT or RHT groups than in the NT group (22 and 20%, respectively, versus 8%; both P < 0.00625). The distribution of eNOS haplotypes was not significantly different in the HT and RHT groups (P > 0.05). CONCLUSIONS: Whereas our findings suggest a protective effect for the 'C Glu b' haplotype against hypertension and that the 'C Asp b' haplotype increases the susceptibility to hypertension, our results suggest that eNOS haplotypes are not associated with resistance to antihypertensive therapy.     

Inheritability of atherosclerosis and the role of lipoproteins as risk factors in the development of atherosclerosis in WHHL rabbits: risk factors related to coronary atherosclerosis are different from those related to aortic atherosclerosis.

Inheritability of atherosclerosis and the influences of serum lipids on atherosclerosis were examined by following its progression in selectively bred WHHL rabbits. Our studies indicate (1) coronary atherosclerosis is clearly inherited from parents by offspring whereas inheritability of aortic atherosclerosis is uncertain; (2) coronary stenosis is positively correlated to serum cholesterol level, although the correlation coefficient is markedly low: in contrast, no relationship between serum lipid levels and aortic atherosclerosis was observed; (3) cholesterol-rich VLDL showed atherogenicity in aorta, but not in coronary arteries; (4) an unknown lipoprotein detected by 3.6% polyacrylamide gel electrophoresis was related to coronary atherosclerosis, although no relationship between the unknown lipoprotein and aortic atherosclerosis was observed. These findings suggest that there are two types of genetic factors involved in atherosclerosis, one of which is unique to coronary atherosclerosis whereas the other is related to only aortic atherosclerosis.     

Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis

Background

Free fatty acids (FFAs) affect insulin signaling and are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines such as interleukin-6 (IL-6) increase lipolysis and thus levels of FFAs. We hypothesized that increased IL-6 concentrations are associated with increased FFAs resulting in insulin resistance and atherosclerosis in rheumatoid arthritis (RA).

Methods

Clinical variables, serum FFAs and inflammatory cytokines, homeostasis model assessment for insulin resistance (HOMA-IR), and coronary artery calcium were measured in 166 patients with RA and 92 controls. We compared serum FFAs in RA and controls using Wilcoxon rank sum tests and further tested for multivariable association by adjusting for age, race, sex and BMI. Among patients with RA, we assessed the relationship between serum FFAs and inflammatory cytokines, HOMA-IR, and coronary artery calcium scores using Spearman correlation and multivariable regression analyses.

Results

Serum FFAs did not differ significantly in patients with RA and controls (0.56 mmol/L [0.38–0.75] and 0.56 mmol/L [0.45–0.70] respectively, p = 0.75). Presence of metabolic syndrome was associated with significantly increased serum FFAs in both RA and controls (p = 0.035 and p = 0.025). In multivariable regression analysis that adjusted for age, race, sex and BMI, serum FFAs were associated with HOMA-IR (p = 0.011), CRP (p = 0.01), triglycerides (p = 0.005) and Framingham risk score (p = 0.048) in RA, but not with IL-6 (p = 0.48) or coronary artery calcium score (p = 0.62).

Conclusions

Serum FFAs do not differ significantly in patients with RA and controls. FFAs may contribute to insulin resistance, but are not associated with IL-6 and coronary atherosclerosis in RA.     

Whole body nitric oxide production is not decreased in patients with coronary atherosclerosis but is inversely related to plasma homocysteine

ObjectiveVascular endothelial nitric oxide (NO) biosynthesis is reported to be decreased in patients with atherosclerosis. The primary aim of the present study was to determine whether whole body NO production is decreased in patients with established coronary atherosclerosis (CA) as compared to healthy control (HC) subjects. As a secondary aim, we wished to ascertain whether whole body NO biosynthesis is inversely related to plasma homocysteine (Hcy) levels.DesignWhole body NO production was assessed by measuring the amount of [¹⁵N]-nitrate excreted in urine, following intravenous administration of l-[¹⁵N]₂-arginine.Subjects19 CA and 13 HC.ResultsMean urinary [¹⁵N]-nitrate excretion was not different between the CA (113.1 ± 13.9 nmol/mmol creatinine) and HC (129.9 ± 15.4 nmol/mmol creatinine) groups, and was not different in CA subjects taking nitrates as compared to those not taking nitrates. Linear regression analysis revealed a strong inverse correlation between [¹⁵N]-nitrate excretion and plasma Hcy concentration (r = 0.475, p = 0.012). In contrast, no relationship was observed between [¹⁵N]-nitrate excretion and age, blood pressure (systolic or diastolic), plasma cholesterol (including subfractions), triglycerides or glucose.ConclusionsWhole body NO production is inversely related to plasma Hcy, but is not related either to established coronary atherosclerosis or to the presence of other cardiovascular risk factors.     

Clinical manifestations of atherosclerosis in an elderly population are related to plasma neopterin, NGAL and endothelin-1, but not to Chlamydia pneumoniae serology.

BACKGROUND: Inflammatory mediators secreted by leukocytes are implicated in atherogenesis. Chlamydia (C.) pneumoniae infection has been suggested as a trigger of this process. We investigated relationships between C. Pneumoniae serology, inflammatory mediators and symptomatic cardiovascular disease in old age. METHODS: In a cross-sectional study at baseline with a prospective 4 year follow-up, intraplatelet cyclic 3'-5'adenosine monophosphate (cAMP) and cyclic 3'-5'guanosine monophosphate (cGMP), plasma neutrophil gelatinase associated lipocalin (NGAL), plasma soluble tumor necrosis factor receptor-1 (TNFR-1) plasma neopterin and plasma endothelin-1 (ET-1) were analysed together with IgG and IgA antibodies for C. Pneumoniae in an elderly reference population (n=140, median age 71 years, 71 females). Twenty-one subjects had clinical manifestations of cardiovascular disease at baseline and another 21 were diagnosed with cardiovascular disease during follow-up. RESULTS: In age adjusted logistic regression, subjects with cardiovascular disease showed higher plasma levels of neopterin (p=0.02), NGAL (p=0.04), and ET-1 (p<0.01). If subjects with cardiovascular disease at baseline were excluded from the analysis, higher plasma neopterin (p=0.01) and lower serum HDL cholesterol (p=0.03) predicted cardiovascular disease during follow-up. The presence of IgG or IgA against C. pneumoniae was not associated with cardiovascular disease. Neither were there any associations between inflammatory or endothelial parameters and C. pneumoniae serology. CONCLUSIONS: The inflammatory mediators neopterin and NGAL and endothelial derived vasoconstrictive ET-1 were increased in elderly subjects with symptomatic cardiovascular disease. Increased plasma neopterin predicted cardiovascular disease during follow-up. No relationships were found between C. Pneumoniae serology and cardiovascular disease.     

冠心病血管内皮功能、颈动脉硬化与冠脉病变的关系

目的：观察冠心病（CAD）患者内皮依赖性舒张功能及颈动脉粥样硬化的状况及与冠状动脉病变的相关性。方法：选经冠状动脉造影确诊为CAD的患者106例（观察组），冠状动脉造影证实无冠状动脉狭窄的健康者40例（正常对照组），采用二维超声检测肱动脉内皮依赖性和非依赖性舒张功能及颈动脉粥样硬化病变。颈动脉粥样硬化斑块积分采用Sutton法，并与冠状动脉病变程度进行对比分析。结果：CAD组内皮依赖性血管舒缩功能（FMD）比正常对照组明显降低（P〈0．01），内皮非依赖性血管舒缩功能与正常对照组比较无显著性差异（P〉0．05）；CAD组颈动脉内膜中层厚度（IMT），斑块积分显著高于正常对照组（P〈0．01）。FMD与冠脉病变程度呈负相关（r=-0．651，P〈0．001），颈动脉IMI及斑块积分与冠脉病变程度呈正相关（r=0．871，0．702，P〈0．001）。结论：内皮细胞功能障碍和颈动脉粥样硬化与冠状动脉粥样硬化的病变相平行。     

Endogenous oestradiol but not testosterone is related to coronary artery disease in men

Objectives Men die of coronary artery disease (CAD) more often than women. There is evidence that testosterone either is neutral or has a beneficial effect on male cardiovascular disease. The role of oestrogens in male CAD has been less studied. This study was carried out with the purpose of evaluating the relationship between sex hormone levels and CAD. Design Case–control study. Participants Men (aged 40–70) submitted to coronary angiography. A 70% occlusion of at least one major coronary artery defined the cases; subjects with ≤50% occlusion constituted the control group. Measurements Blood samples were collected for total testosterone (TT), oestradiol, luteinizing hormone, follicle‐stimulating hormone, sex hormone‐binding globulin, lipid profile and albumin measurements. Bioavailable and free testosterone, free androgen index (FAI) and free oestrogen index (FEI) were calculated. Oestradiol and TT levels were examined as terciles, based on the whole study population. Results Of the 140 patients included, 72 were cases and 68 were controls. The baseline characteristics of the two groups were similar, except for the older age and lower LDL‐C in the cases. Oestradiol and FEI but not total, bioavailable and free testosterone and FAI correlated positively with CAD. After adjustments for potential confounders, oestradiol remained statistically significant. The prevalence of CAD was significantly higher in the 3rd than in the 1st tercile of oestradiol. Conclusion In this study, men with CAD had higher oestradiol and FEI levels. Additional studies are needed to clarify the direction of causality and possible underlying mechanisms.     

Serum potassium concentrations are inversely related to ventricular, but not to atrial, arrhythmias in acute myocardial infarction

In a study of 1033 consecutive patients with acute myocardialinfarction, serum potassium concentrations were determined onadmission to hospital and studied with respect to the subsequentoccurrence of atrial fibrillation and flutter and of ventriculartachycardia and fibrillation. The study cohort fulfilled theinclusion criteria for the Norwegian timolol trial in whichthey later took part. In multivariate analysis, with serum potassiumconcentrations as a continuous variable, age, the presence ofventricular tachycardia and fibrillation, and maximum levelof aspartate aminotransferase greater than four times the upperlimit of normal were significantly associated with the occurrenceof atrial fibrillation and flutter, while serum potassium concentrationwas not. Serum potassium concentrations and time from onsetof the infarction to hospital admission were significantly negativelyassociated with the occurrence of ventricular tachycardia andfibrillation; while age, cardiomegaly, transient hypotension,pathological Q-waves in the electrocardiogram, atrial fibrillationand flutter, and ventricular premature beats were positivelyrelated to these arrhythmias.     

Epidemiological risk factors of coronary heart disease are not causal in atherosclerosis

Logic dictates that for scientific progress in atherogenesis "cause" must be the sole prequisite without which the disease cannot occur. Nor can it be assumed that statistical associations (risk factors) with coronary heart disease (CHD) are causal for atherosclerosis and extrapolations from correlations with CHD incidence to atherosclerosis are invalid. Any factor considered to play a role in atherogenesis requires pathological and experimental evidence consistent with the logic of Koch's specificity of cause and effect. Current epidemiological misuse and manipulation of cause and risk factors are contrary to the basic precepts of scientific logic and the fundamental need for precision in word usage. The term "risk factor", because of the current deeply entrenched false concept of causality has retarded medical progress and should be abandoned. Its adherents, guilty of a disservice to the tenets of their discipline, have also sullied the scientific integrity of medicine as a whole.     

Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.     

冠状动脉粥样硬化相关生物力学因素的研究进展

冠状动脉是动脉粥样硬化最早发和最好发的部位,严重的冠状动脉粥样硬化可造成心肌缺血、心肌梗死,危害人们健康。相比人体其他部位动脉,冠状动脉具有独特的解剖结构和血流动力学特征,这些特征与其粥样硬化发生具有明显的相关性。文章就冠状动脉粥样硬化相关生物力学因素作一综述。