Phytosterols supplementation decreases plasma small and dense LDL levels in metabolic syndrome patients on a westernized type diet.

BACKGROUND AND AIMS: Several studies have observed a hypocholesterolemic effect of plant sterols in hypercholesterolemic patients on a balanced diet. The aim of this study was to examine the effect of phytosterol supplementation on risk factors of coronary artery disease in metabolic syndrome patients on a Westernized type diet. METHODS AND RESULTS: In a randomized placebo-controlled design 108 patients with metabolic syndrome were assigned to consume either 2 plant sterol-enriched yogurt mini drink which provided 4 g phytosterols per day, or a yogurt beverage without phytosterols (control). The duration of the study was 2 months and the patients in both groups followed their habitual westernized type diet and recording it on food diaries. Blood samples were drawn at baseline and after 2 months of intervention. After 2 months supplementation with phytosterols, a significant reduction in total cholesterol, LDL-cholesterol, small and dense LDL (sdLDL) levels, as well as, apoB and triglycerides concentrations were observed in the intervention group (P < 0.05) compared to the control group. In addition, phytosterol supplementation lowered serum total cholesterol by 15.9%, LDL-cholesterol by 20.3% and triglyceride levels by 19.1% (P = 0.02, P < 0.001 and P < 0.001, respectively), although the patients kept their habitual westernized type diet. No differences were observed in HDL cholesterol, apoA1, glucose, C-reactive protein, fibrinogen levels and blood pressure. CONCLUSIONS: Phytosterol supplementation improves risk factors of coronary artery disease even if the diet is a westernized type.

Linkage disequilibrium in the human genome.

With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting 'haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1-3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000-53,000 years ago.

In-hospital mortality of habitual cigarette smokers after acute myocardial infarction; the "smoker's paradox" in a countrywide study.

AIMS: Habitual cigarette smokers, paradoxically, present improved short-term prognosis after acute myocardial infarction, a phenomenon often termed "smoker's paradox". We sought to examine cigarette smokers' post-infarction survival advantage in a countrywide survey of unselected, consecutive patients presenting with acute myocardial infarction. METHODS AND RESULTS: The study population was derived from the registry of the Hellenic study of acute myocardial infarction, which recruited 7433 consecutive patients with acute myocardial infarction from 76, out of a total of 86, hospitals countrywide. Cigarette smokers presented with lower unadjusted mortality rates (7.4% vs 14.5%, P<0.001), were younger, predominantly of male gender and were less likely to suffer from diabetes mellitus and arterial hypertension. When all univariate predictors of poor outcome were included as covariates in multivariate analysis, smoking status was not significantly associated with inhospital mortality (relative risk=1.12, 95% CI=0.86-1.44, P=0.399). The beneficial effect of thrombolytic therapy was independent of the smoking status in both univariate and multivariate analysis. CONCLUSION: Unadjusted mortality rates are significantly lower in smokers, but age accounted for much of their seemingly improved outcome. When a number of additional clinical variables were taken into consideration, no significant influence of habitual smoking on early outcome following acute myocardial infarction was observed.

Increased variance of P wave duration on the electrocardiogram distinguishes patients with idiopathic paroxysmal atrial fibrillation.

We hypothesized that the variance of P wave duration (P variance) in the 12-lead ECG could reflect the spatial dispersion of P wave duration due to inhomogeneous and delayed propagation of sinus impulses in the atria, and moreover could present better reproducibility than maximum P wave duration and P wave dispersion that have already been used for the prediction of idiopathic paroxysmal AF. We also tested a semiautomated PC-based method to improve the accuracy and reproducibility of P wave measurements. A 12-lead ECG was obtained from 60 patients with idiopathic paroxysmal AF and from 50 healthy controls. All ECGs were analyzed manually using magnifying lens and calipers, while 20 randomly selected ones were scanned and analyzed on screen using common commercial software. P maximum, P dispersion, and P variance were all significantly higher in patients with paroxysmal AF than in controls. A P maximum value of 110 ms, a P dispersion value of 40 ms, and a P variance value of 120 ms2 separated patients from controls with a sensitivity of 88%, 83%, and 80%, respectively and a specificity of 75%, 85%, and 74%, respectively. The reproducibility of P variance was higher compared to P dispersion and P maximum. Finally, the PC-based method significantly increased accuracy and reproducibility of P wave measurements. Thus, the variance of P wave duration could be a useful ECG marker for the prediction of paroxysmal idiopathic AF and the use of PC-based methods may enhance the accurate measuring of P wave duration on the ECG.

The role of carotid atherosclerosis in the distinction between ischaemic and non-ischaemic cardiomyopathy.

AIM: Sometimes ischaemic cardiomyopathy is a result of severe coronary artery disease of an occult course, without typical symptoms or evidence of myocardial infarction. This form of presentation is usually indistinguishable from non-ischaemic dilated cardiomyopathy. Carotid bifurcation atherosclerosis and coronary artery disease have been shown to be strongly associated. We prospectively examined the value of extracranial carotid atherosclerosis in the distinction between ischaemic and non-ischaemic aetiology in patients with clinically unexplained cardiomyopathy. METHODS AND RESULTS: Seventy-eight patients with undetermined dilatation and diffuse impairment of the left ventricular contraction were studied within 28 months. They underwent carotid scan and coronary arteriography. Carotid atherosclerosis was found to be very common in ischaemic and rare in non-ischaemic cardiomyopathy. The presence of at least one abnormal carotid finding (intima-media thickness >1 mm, plaques, severe carotid stenosis) was 96% sensitive and 89% specific for ischaemic cardiomyopathy. CONCLUSION: Carotid scanning may be a useful screening and decision making tool in patients with cardiomyopathy of indecisive cause. Patients with carotid atherosclerosis are likely to suffer from severe coronary artery disease. Coronary angiography and subsequent myocardial viability studies, when indicated, could be considered early during their evaluation. In contrast, a negative carotid scan predicts non-ischaemic cardiomyopathy.

Clinical and electrocardiographic predictors of recurrent atrial fibrillation.

Patients with frequent episodes of paroxysmal atrial fibrillation (AF) are prone to develop permanent AF and have an increased thromboembolic risk. We have previously shown that P wave dispersion (P dispersion), defined as the difference between the maximum and the minimum P wave duration, and maximum P wave duration (P maximum) can distinguish patients with paroxysmal lone AF. The ability of those ECG markers and of other clinical and ECG variables to detect patients at risk for recurrent AF was tested in 88 patients, aged 64 +/- 12 years. All patients had a history of symptomatic episodes of AF during the last 2 years and had not previously received any antiarrhythmic prophylaxis. P maximum and P dispersion were calculated from a 12-lead surface ECG recorded in all patients during sinus rhythm. A computerized ECG system was used and P maximum and P dispersion were calculated on screen from the averaged complexes of all 12 leads. Age (P = 0.01), history of organic heart disease (P = 0.03), P maximum (P < 0.001), minimum P wave duration (P = 0.05), and P dispersion (P < 0.001) were found to be significant univariate predictors of recurrent AF, whereas only P maximum (P < 0.001) and age (P = 0.037) remained significant independent predictors of frequent AF paroxysms in the multivariate analysis. It is concluded that advanced age and prolonged P wave duration may be used as predictors of frequently relapsing AF. Therefore, simple AF predictors exist that could possibly distinguish the patients in whom prophylaxis with antiarrhythmic medicines should be instituted.

Effects of ischemia on P wave dispersion and maximum P wave duration during spontaneous anginal episodes.

P wave dispersion (P dispersion), defined as the difference between the maximum and the minimum P wave duration, and maximum P wave duration (P maximum) are electrocardiographic (ECG) markers that have been used to evaluate the discontinuous propagation of sinus impulses and the prolongation of atrial conduction time, respectively. To study the effects of myocardial ischemia on P dispersion and P maximum, 95 patients with coronary artery disease (CAD) and typical angina pectoris and 15 controls with angina like symptoms underwent 12-lead surface ECG during and after the relief of pain. During pain and during the asymptomatic period, P maximum and P dispersion were calculated from the averaged complexes of all 12 leads. P dispersion increased significantly during spontaneous angina (45+/-17 ms) compared to the asymptomatic period (40+/-15 ms), P < 0.001 only in the patient group. Both P maximum and P dispersion showed higher values during angina in those patients who developed diffuse ischemia, as estimated with ST segment changes in multiple ECG leads. P dispersion showed higher values during the anginal episode in patients with left ventricular dysfunction, independently of the presence of a previous myocardial infarction. Atrial conduction abnormalities, as estimated with P maximum and particularly P dispersion, are significantly influenced by myocardial ischemia in patients with CAD and spontaneous angina.

Detection of hypertensive patients at risk for paroxysmal atrial fibrillation during sinus rhythm by computer-assisted P wave analysis.

OBJECTIVE AND METHODS: To determine whether hypertensive patients at risk for paroxysmal atrial fibrillation (AF) could be detected while in sinus rhythm, a computer-based 12-lead surface electrocardiogram was recorded in 50 hypertensive patients with history of paroxysmal AF (group A) and in 60 hypertensive patients without history of AF (group B). The maximum P-wave duration (P(maximum)), the minimum P-wave duration (P(minimum)), P-wave dispersion (Pdispersion = Pmaximum Pminimum), adjusted P-wave dispersion (APdispersion = Pdispersion/square root of the number of measurable leads), mean P-wave duration (mean P) and the standard deviation of the P-wave duration in all measured leads (SDP) were calculated. RESULTS: Pdispersion, APdispersion and SDP were significantly higher in group A than in group B (Pdispersion, 52 +/- 19 versus 41 +/- 15 ms, P< 0.001; APdispersion, 15.2 +/- 5.5 versus 11.9 +/- 4.6 ms, P< 0.001; SDP, 16 +/- 5 versus 13 +/- 5 ms, P < 0.001). P(minimum), mean P and left ventricle ejection fraction (LVEF) were significantly lower in group A than in group B (Pminimum, 79 +/- 18 versus 91 +/- 13 ms, P < 0.001; mean P, 108 +/- 18 versus 116 +/- 13 ms, P= 0.005; LVEF, 64 +/- 5 versus 69 +/- 8%, P< 0.001). Pminimum, Pdispersion, mean P, SDP, APdispersion and LVEF were found to be significant univariate predictors of paroxysmal AF, whereas only Pminimum (P< 0.001) remained a significant independent predictor of paroxysmal AF in the multivariate analysis. CONCLUSION: Hypertensive patients at risk for paroxysmal AF could be detected while in sinus rhythm by computer-assisted electrocardiographic P-wave analysis.

Significance of exercise-induced simultaneous ST-segment changes in lead aVR and V5.

This study was undertaken to investigate the ability of the exercise-induced ST depression in lead V5 and concomitant ST elevation in lead aVR for the identification of the significantly narrowed coronary artery in patients with single vessel disease. We studied 229 consecutive patients who developed the aforementioned exercise-induced electrocardiographic changes. All underwent Thallium-201 scintigraphy and coronary arteriography. Patients were divided into three groups. In group A, 58 patients with ST depression in V5 and ST elevation in aVR, in group B 149 patients with ST depression in V5 without ST elevation in aVR, and in group C 22 patients with ST elevation in aVR without ST depression in V5 induced with exercise, were included. In group A, 81% of the patients while in group B, 29% and in group C only 18% of the patients had left anterior descending artery disease. According to Thallium-201 scintigraphy, 80% of the group A, 27% of the group B and 12% of the group C patients developed myocardial ischemia in areas supplied by the left anterior descending artery. Thus, exercise-induced ST depression in V5 and concomitant ST elevation in aVR, may detect left anterior descending artery significant stenosis in patients with single vessel disease.

QRS prolongation on the signal-averaged electrocardiogram versus ST-segment changes on the 12-lead electrocardiogram: which is the most sensitive electrocardiographic marker of myocardial ischemia?

BACKGROUND: ST-segment changes and QRS prolongation are electrocardiographic (ECG) markers of myocardial ischemia. HYPOTHESIS: This study was undertaken to investigate the appearance of QRS duration changes with or without concomitant ST-segment changes during a typical anginal episode. METHODS: For this purpose, 126 patients underwent 12-lead surface ECG and signal-averaged electrocardiogram (SAECG) during typical anginal pain as well as at the time the patient was asymptomatic. In both periods, QRS duration and ST-segment changes were evaluated. All patients underwent cardiac catheterization. RESULTS: Of the 126 patients, 108 (86%) had coronary artery disease (CAD), whereas the remaining 18 (14%) patients had normal coronary arteriograms. During typical anginal pain, 75 of the 108 (70%) patients with CAD and 2 of the 18 (11%) patients with normal coronary arteriograms developed QRS prolongation, whereas 60 of the 108 (56%) patients with CAD and 2 of the 18 (11%) patients with normal coronary vessels developed ST-segment changes. Thus, the sensitivities of QRS prolongation measured by SAECG and of ST-segment changes on the surface ECG for the detection of myocardial ischemia were found to be 70 and 56%, respectively, (p < 0.01), whereas the specificities were both found to be 89% (p = NS). CONCLUSIONS: During typical anginal pain, QRS prolongation on the SAECG is more sensitive than are ST-segment changes on the ECG for the detection of myocardial ischemia.

Exercise-induced ST-segment changes in lead V1 identify the significantly narrowed coronary artery in patients with single-vessel disease: correlation with thallium-201 scintigraphy and coronary arteriography data.

We investigated the correlation of exercise-induced ST-segment changes in lead V1, with the detection of the significantly narrowed vessel that induced ischemia during exercise in myocardial areas supplied by this vessel. We studied 198 patients who underwent exercise testing, thallium-201 scintigraphy, and coronary arteriography. The patients were divided into three groups. In group 1 (ST-segment elevation in lead V1), 84% had left anterior descending coronary artery disease (P<.001); in group 2 (ST-segment depression in lead V1), 76% had right coronary artery disease (P<.001); and in group 3 (no ST-segment changes in lead V1), there were no significant differences concerning the narrowed vessel. Thallium-201 scintigraphy data confirmed the existence of the reversible perfusion defect(s) in an area(s) of myocardium supplied by the respective coronary arteries (P<.001). Exercise-induced ST-segment elevation or depression in V1 may identify the obstructed vessel in patients with single-vessel disease and without prior myocardial infarction.

Improved detection of coronary artery disease by exercise electrocardiography with the use of right precordial leads.

BACKGROUND: Exercise electrocardiography is an perfect test for the detection of coronary artery disease. We attempted to improve the diagnostic accuracy of exercise testing as a noninvasive method for the detection of coronary artery disease by using a combination of the left and right precordial leads. METHODS: We studied 245 patients (218 men and 27 women) ranging from 32 to 74 years of age (mean [+/-SD], 52+/-8) who underwent treadmill exercise testing, thallium-201 scintigraphy, and coronary arteriography. During exercise testing, each patient had one electrocardiogram recorded with the standard 12 leads and 3 right precordial leads (V3R, V4R, and V5R), with the results for each set of leads recorded and analyzed separately. RESULTS: On the basis of coronary arteriography, 34 patients had normal coronary arteries, 85 had single-vessel disease, 84 had two-vessel disease, and 42 had three-vessel disease. The sensitivities of the standard 12-lead exercise electrocardiogram, exercise electrocardiography incorporating right precordial leads, and thallium-201 scintigraphy were 52 percent, 89 percent, and 87 percent, respectively, for the detection of single-vessel disease; 71 percent, 94 percent, and 96 percent for the detection of two-vessel disease; 83 percent, 95 percent, and 98 percent for the detection of three-vessel disease; and 66 percent, 92 percent, and 93 percent for the detection of any coronary artery disease. The specificities of the three methods for the detection of any coronary artery disease were 88 percent, 88 percent, and 82 percent, respectively. CONCLUSIONS: Use of right precordial leads along with the standard six left precordial leads during exercise electrocardiography greatly improves the sensitivity of exercise testing for the diagnosis of coronary artery disease.