EFT VENTRICULAR HYPERTROphy (LVH) detected by 12lead electrocardiogram (ECG) 1-3 and by echocardiography 4-8 are common manifestations of preclinical cardiovascular (CV) disease that strongly predict CV morbidity and mortality. Antihypertensive therapy aimed at reducing blood pressure (BP) can produce regression of LVH 3,4,9-15 and reduces but does not entirely eliminate the increased risk of major CV events. 16-20 However, whether regression of electrocardiographic LVH per se is associated with improved prognosis independent of improvements in See also pp 2350 and 2396 and Patient Page.

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P2 receptors mediate the actions of the extracellular nucleotides ATP, ADP, UTP, and UDP, regulating several physiologic responses including cardiac function, vascular tone, smooth muscle cell (SMC) proliferation, platelet aggregation, and the release of endothelial factors. P2 receptor characterization has been hampered by the lack of selective antagonists. The aim of the current study was to investigate the mRNA and protein expression of P2X and P2Y receptors in human SMC and in endothelial cells (EC). Smooth muscle cells were obtained from human mammary artery and EC from human umbilical vein. Using real-time PCR, the authors established quantitative mRNA assays. Protein expression was studied using Western blotting with recently developed antibodies. The P2X1 receptor was highly specific for human SMC, while the P2X4 was the highest expressed receptor in EC. The P2Y2 receptor was present in both SMC and EC. UTP-mediated effects in these cells are likely to be mediated by P2Y2 and not P2Y4 receptors since the latter had considerably lower expression. The P2Y6 receptor was expressed in both SMC and EC. The P2Y1 and surprisingly the P2Y11 receptors were the most abundantly expressed P2Y receptors in the endothelium. Overall, Western blotting confirmed the mRNA findings in most aspects, and most interestingly, indicated oligomerization of the P2Y1 receptor that may be important for its function. In conclusion, P2X1, P2Y2, and P2Y6 are the most expressed P2 receptors in SMC and are thus probably mediating the contractile and mitogenic actions of extracellular nucleotides. The P2X4, P2Y11, P2Y1, and P2Y2 are the most expressed P2 receptors in EC, and are most likely mediating release of nitric oxide, endothelium-dependent hyperpolarizing factor (EDHF), and t-PA induced by extracellular nucleotides. These findings will help to direct future cardiovascular drug development against the large P2 receptor family.

Lower Cornell product electrocardiographic LVH during antihypertensive therapy is associated with a lower likelihood of new-onset AF, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may reduce the incidence of new-onset AF.

Previous studies have suggested that plasminogen activator inhibitor 1 (PAI-1) released from platelets convey resistance of platelet-rich blood clots to thrombolysis. However, the majority of PAI-1 in platelets is inactive and therefore its role in clot stabilization is unclear. Because platelets retain mRNA and capacity for synthesis of some proteins, we investigated if platelets can de novo synthesize PAI-1 with an active configuration. PAI-1 mRNA was quantified with real-time polymerase chain reaction and considerable amounts of PAI-1 mRNA were detected in all platelet samples. Over 24 hours, the amount of PAI-1 protein as determined by an enzyme-linked immunosorbent assay increased by 25% (P ‫؍‬ .001). Metabolic radiolabeling with 35 S-methionine followed by immunoprecipitation confirmed an ongoing PAI-1 synthesis, which could be further stimulated by thrombin and inhibited by puromycin. The activity of the newly formed PAI-1 was investigated by incubating platelets in the presence of tissue-type plasminogen activator (tPA).This functional assay showed that the majority of the new protein was in an active configuration and could complexbind tPA. Thus, there is a continuous production of large amounts of active PAI-1 in platelets, which could be a mechanism by which platelets contribute to stabilization of blood clots. (Blood. 2004; 104:3943-3948)

SummaryTo study the effects of standardized mental stress (arithmetic and the Stroop color word test) on plasma coagulation and fibrinolysis, blood samples were obtained before, during, and after 20 minutes of mental stress from 10 healthy, non-smoking young males aged 22 to 30 years. Reactions were compared with those observed during physical exercise and infusion of adrenaline. Both von Willebrand factor antigen and factor VIII coagulant activity increased significantly in response to mental stress (95 ± 28 vs 123 + 56%; p <0.05 and 125 ±54 vs 217 ± 170%; p <0.05, respectively). There was also a significant increase of factor VII coagulant activity (86 ± 31 vs 108 + 51%; p <0.05). Furthermore, mental stress caused an activation of the fibrinolytic system with an elevation of tissue plasminogen activator activity and tissue plasminogen activator antigen (0.80 ± 0.48 vs 1.23 ± 0.96 IU/ml; p = 0.076 and 4.38 ± 1.87 vs 5.78 ± 2.58 IU/ml; p <0.01). Fibrinogen concentration increased during stress (1.95 ± 0.29 vs 2.11 ± 0.27 g/1; p <0.05). Similar but more pronounced responses were observed during exercise and adrenaline infusion. Parallel to the increases in coagulation and fibrinolytic factors there were significant increases in heart rate, and systolic and diastolic blood pressure. It is concluded that mental stress has significant effects on plasma coagulation and fibrinolysis, and that it could thus affect important risk factors for cardiovascular disease.

Abstract-The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear.ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol-or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V 5 and/or V 6 and was present in 971 patients (11.0% Key Words: coronary disease Ⅲ electrocardiography Ⅲ hypertension T he classic strain pattern of ST depression and T-wave inversion on the ECG is a well recognized marker of the presence of anatomic left ventricular hypertrophy (LVH), 1-7 independent of the possible relationship of this repolarization abnormality to underlying coronary heart disease. 7 Indeed, the presence of even minimal degrees of ST depression in the lateral precordial leads is associated with increased LV mass and prevalence of anatomic LVH when repolarization is examined quantitatively on digital ECGs. 8 Incorporation of ECG strain into scores that include standard voltage criteria improves ECG detection of LVH. 2,6 ECG strain has also been associated with adverse prognosis in a variety of clinical populations, 9 -15 including patients with hypertension, 9,10 and implicated as the primary marker of untoward outcomes when ECG LVH criteria have been used for risk stratification. 9 -13 However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality after adjusting for the type and effectiveness of antihypertensive therapy is unclear.The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study demonstrated that therapy with losartan was more effective than atenolol in preventing CV morbidity and mortality in the setting of large and nearly identical reductions in systolic and diastolic pressure in both treatment arms. 16 In the prespecified echocardiographic substudy of the LIFE study, strain on the baseline ECG was associated with greater LV mass and a higher prevalence of LVH, 7 suggesting that ECG strain may also be associated with an increased risk of CV morbidity and mortality in LIFE. Therefore, the present study examined the relation of the strain pattern on the baseline ECG to major CV events in the LIFE study, independent of the effects of treatment type, baseline severity of hypertension and ECG LVH, and other potential risk factors. 16

Abstract-Left ventricular hypertrophy is a risk factor for cardiovascular mortality, including sudden cardiac death.Experimentally, left ventricular hypertrophy delays ventricular conduction and prolongs action potential duration. Electrocardiographic QRS duration and QT interval measures reflect these changes, but whether these measures can further stratify risk in patients with electrocardiographic left ventricular hypertrophy is unknown. We measured the QRS duration and QT intervals from the baseline 12-lead electrocardiograms in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, which included hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy randomized to either losartan-based or atenolol-based treatment to lower blood pressure. In the present study, we related study baseline electrocardiographic measures to cardiovascular and all-cause mortality. There were 5429 patients (male 45.8%; mean age 66Ϯ7 years) included in the present analyses. After a mean follow-up of 4.9Ϯ0.8 years, there were 417 deaths from all causes, including 214 cardiovascular deaths. In separate univariate Cox regression analyses, QRS duration and several QT measures were significant predictors of cardiovascular mortality and all-cause mortality. However, in multivariate Cox analyses including all electrocardiographic measures and adjusting for other risk factors as well as treatment strategy, only QRS duration and maximum rate-adjusted QT apex interval remained as significant independent predictors of cardiovascular (Pϭ0.022 and Pϭ0.037, respectively) and all-cause mortality (Pϭ0.038 and Pϭ0.002, respectively). In conclusion, in a hypertensive risk population identified by electrocardiographic left ventricular hypertrophy, increased QRS duration and maximum QT apex interval can further stratify mortality risk even in the setting of effective blood pressure-lowering treatment. Key Words: electrocardiography Ⅲ hypertension Ⅲ mortality Ⅲ hypertrophy L eft ventricular hypertrophy (LVH) is an important indicator of target organ damage in chronic arterial hypertension. Electrocardiographically and echocardiographically detected LVH independently predict increased morbidity and mortality, 1,2 including sudden cardiac death, 3,4 and the relative risk of these events increases with increasing LV mass. The impact of LVH on outcome may in part be mediated by adverse changes in LV mechanical function. However, LVH also induces potentially arrhythmogenic changes in LV electrophysiology. Experimental evidence shows that LVH alters ventricular conduction and repolarization. [5][6][7][8][9][10][11][12][13][14] In the 12-lead ECG, these changes may prolong the QRS and QT interval duration, respectively, and affect T-wave morphology. [15][16][17] In hypertensive patients with ECG LVH, increase in LV mass was associated with prolonged QRS and QT interval duration and measures of QT dispersion. 18 However, it is unknown if these ECG measures can further stratify risk in patients with LVH. T...