Effect of endurance training on blood pressure regulation, biomarkers and the heart in subjects at a higher age.

We reported previously that two otherwise identical training programs at lower (LI) and higher intensity (HI) similarly reduced resting systolic blood pressure (BP) by approximately 4-6 mmHg. Here, we determined the effects of both programs on BP-regulating mechanisms, on biomarkers of systemic inflammation and prothrombotic state and on the heart. In this cross-over study (3 × 10 weeks), healthy participants exercised three times 1 h/week at, respectively, 33% and 66% of the heart rate (HR) reserve, in a random order, with a sedentary period in between. Measurements, performed at baseline and at the end of each period, involved blood sampling, HR variability, systolic BP variability (SBPV) and cardiac magnetic resonance imaging. Thirty-nine participants (18 men; mean age 59 years) completed the study. Responses were not different between both programs (P>0.05). Pooled data from LI and HI showed a reduction in HR (-4.3 ± 8.1%) and an increase in stroke volume (+11 ± 23.1%). No significant effect was seen on SBPV, plasma renin activity, basal nitric oxide and left ventricular mass. Our results suggest that the BP reduction observed appears to be due to a decrease in systemic vascular resistance; training intensity does not significantly affect the results on mechanisms, biomarkers and the heart.

Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial.

OBJECTIVE: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure. DESIGN: Single centre double-blind randomized placebo controlled trial. SETTING: Cardiac rehabilitation centre. SUBJECTS AND INTERVENTION: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation. MAIN MEASURES: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed. RESULTS: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P<0.05 for all). However, changes after training were similar between placebo group and creatine group (P>0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects. CONCLUSION: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone.

Identification of a novel p53-dependent activation pathway of STAT1 by antitumour genotoxic agents.

Chemotherapeutic drugs such as fludarabine*, doxorubicin or cisplatin are very potent activators of the anti-oncogene p53. Convergent studies suggest that p53 and STAT1 (signal transducer and activator of transcription 1) cooperate in the induction of cell death. We show that these drugs are also activators of STAT1 in p53-expressing cells, but not in p53-null cells. STAT1 activation was obtained in the presence of both the secretion inhibitor brefeldine A and the inhibitor of RNA synthesis, actinomycin D. p53-dependent STAT1 activation was reversed by overexpression of MDM2 and siRNAs against p53. Genetic analysis of p53 showed that expression of transcriptionally inactive p53 punctual mutants markedly increased Y701-STAT1 phosphorylation, and suggests that the p53 DNA-binding domain was alternatively involved in STAT1 activation or p53 multimerization. Immunoprecipitation experiments showed that ataxia telangiectasia mutated, p53, STAT1 and c-Abl1 (Abelson murine leukaemia viral oncogene homologue 1) were associated together. Treatment of cells with the c-Abl1 tyrosine kinase inhibitor STI571 decreased STAT1 activation by genotoxic drugs. Finally, genotoxic agents sensitized cells in response to very low doses of both interferon alpha and gamma (IFNalpha and gamma). These results show that genotoxic drugs induce STAT1 activation, an effect that depends on p53 protein but not on p53 transcriptional activity, and point to a novel pathway of STAT1 activation by genotoxic drugs, with involvement of c-Abl1 tyrosine kinase in sensitizing cells to IFN response.

Parent-of-origin specific linkage and association of the IGF2 gene region with birth weight and adult metabolic risk factors.

OBJECTIVE: The maternally imprinted insulin-like growth factor 2 (IGF2) gene is an important fetal growth factor and is also suggested to have postnatal metabolic effects. In this study, we examined whether common polymorphisms in IGF2 (6815_6819delAGGGC, 1156T>C and 820G>A (ApaI)) and a microsatellite marker in the close vicinity of IGF2 were linked to or associated with birth weight and adult metabolic risk factors. DESIGN AND PARTICIPANTS: Polymorphisms were genotyped in 199 monozygotic complete twin pairs, 109 dizygotic complete twin pairs, 15 single twins, 231 mothers and 228 fathers recruited from the East Flanders Prospective Twin Survey. Conventional and parent-of-origin specific linkage and association analyses were carried out with birth weight, adult body height and parameters quantifying obesity, insulin sensitivity and dyslipidaemia measured at adult age (mean age 25 years). RESULTS: In the parent-of-origin specific association analysis, in which only the paternally inherited allele was incorporated, the 1156T>C SNP (single nucleotide polymorphism) showed significant association with IGF-binding protein 1 (IGFBP1) levels (T and C (mean (95% CI)): 13.2 (12.1-14.3) and 16.2 (14.6-18.0) ng ml(-1), P=0.002). No linkage was observed in either the conventional or in the parent-of-origin specific linkage analysis. CONCLUSION: This study suggests that paternally inherited alleles of a common polymorphism in the IGF2 gene affect IGFBP1 levels.

The protein tyrosine kinase p56lck inhibits CD4 endocytosis by preventing entry of CD4 into coated pits.

The lymphocyte glycoprotein CD4 is constitutively internalized and recycled in nonlymphoid cells, but is excluded from the endocytic pathway in lymphocytic cells (Pelchen-Matthews, A., J. E. Armes, G. Griffiths, and M. Marsh. 1991. J. Exp. Med. 173: 575-587). Inhibition of CD4 endocytosis is dependent on CD4 expressing an intact cytoplasmic domain and is only observed in cells where CD4 can interact with the protein tyrosine kinase p56lck, a member of the src gene family. We have expressed p56lck, p60c-src, or chimeras of the two proteins in CD4-transfected NIH-3T3 or HeLa cells. Immunoprecipitation of CD4 and in vitro kinase assays showed that p56lck and the lck/src chimera, which contains the NH2 terminus of p56lck, can associate with CD4. In contrast, p60c-src and the src/lck chimera, which has the NH2 terminus of p60c-src, do not associate with CD4. Endocytosis assays using radioiodinated anti-CD4 monoclonal antibodies demonstrated that coexpression of CD4 with p56lck, but not with p60c-src, inhibited CD4 endocytosis, and that the extent of the inhibition depended directly on the relative levels of CD4 and p56lck expressed. The uptake of mutant CD4 molecules which cannot interact with p56lck was not affected. Measurement of the fluid-phase endocytosis of HRP or the internalization of transferrin indicated that the effect of p56lck was specific for CD4, and did not extend to other receptor-mediated or fluid-phase endocytic processes. Immunogold labeling of CD4 at the cell surface and observation by electron microscopy demonstrated directly that p56lck inhibits CD4 endocytosis by preventing its entry into coated pits.

Arterial properties in relation to genetic variation in alpha-adducin and the renin-angiotensin system in a White population.

Earlier studies have demonstrated the interaction between ADD1 and ACE in relation to arterial properties. We investigated whether arterial characteristics might also be related to interactions of ADD1 with other renin-angiotensin system genes. Using a family-based sampling frame, we randomly recruited 1064 Flemish subjects (mean age, 43.6 years; 50.4% women). By means of a wall-tracking ultrasound system, we measured the properties of the carotid, femoral and brachial arteries. In multivariate-adjusted analyses, we assessed the multiple gene effects of ADD1 (Gly460Trp), AGT (C-532T and G-6A) and AT1R (A1166C). In ADD1 Trp allele carriers, but not in ADD1 GlyGly homozygotes (P-value for interaction < or =0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm(2) kPa(-1); P=0.020) in carriers of the AT1R C allele than in AT1R AA homozygotes, with a similar trend for femoral distensibility (11.3 vs 10.2 x 10(-3) kPa(-1); P=0.055). These associations were independent of potential confounding factors, including age. Family-based analyses confirmed these results. Brachial diameter (4.35 vs 4.18 mm) and plasma renin activity (PRA) (0.23 vs 0.14 ng ml(-1) h(-1)) were increased (P< or =0.005) in AGT CG haplotype homozygotes compared with non-carriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 x 10(-3) kPa(-1); P=0.011). There was no interaction between AGT and any other gene in relation to the measured phenotypes. ADD1 and AT1R interactively determine the elastic properties of the femoral artery. There is a single-gene effect of the AGT promoter haplotypes on brachial properties and PRA.

[The good use of home blood pressure monitoring. Consensus document]. / Document de consensus. Du bon usage de l'automesure tensionnelle.

Self or home blood pressure measurement (HBPM) is increasingly popular. Its prognostic value and clinical interest in the diagnosis and follow-up of hypertension are well established. In addition, experts widely agree on the fact that it improves hypertension management and therapeutic compliance. In particular, HBPM often allows to detect white coat hypertension (to be confirmed by 24-hour ambulatory blood pressure measurement). Unfortunately, a large part of HBPM devices in the European Union have not fulfilled independent validation criteria. Furthermore, many patients buy and use such devices without medical supervision. This consensus document summarizes the advantages and disadvantages of HBPM and the conditions of a proper use, in agreement with the recent European and American guidelines.

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins.

OBJECTIVE: Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G>A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins. DESIGN: SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models. RESULTS: The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465-2557), 2575 (2516-2635) and 2726 (2606-2845) gram; P(additive)=0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431-2554), 2545 (2495-2595) and 2655 (2571-2740) gram; P(additive)=0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P=0.014). G allele carriers of the LEP 19G>A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58-1.66) vs 1.49 (1.40-1.58) mmol l(-1); P(recessive)=0.013). CONCLUSIONS: This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G>A SNP affect HDL cholesterol levels.

Intra-erythrocyte cation concentrations in relation to the C1797T beta-adducin polymorphism in a general population.

Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na(+) [iNa], K(+) [iK] and Mg(2+) [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy-Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R(2)=0.128) increased with age and serum Na(+), but decreased with serum total calcium and the daily intake of alcohol. iMg (R(2)=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P

Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer.

BACKGROUND: Microsatelite instability (MSI) is the consequence of the inactivation of a mismatch repair gene and is observed in approximately 15% of colon cancer cases. Patients with MSI colon cancer do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5-FU and oxaliplatin (FOLFOX). The aim of this study was to determine the efficiency of the FOLFOX treatment in patients with metastatic MSI colon cancer. PATIENTS AND METHODS: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX 4 modified or FOLFOX 6; these two regimens are based on 85 mg/m2 and 100 mg/m2 oxaliplatin, respectively. The MSI status was assessed by measuring the length of five monomorphic mononucleotide markers. The FOLFOX regimen was evaluated as a first-line treatment according to WHO criteria. RESULTS: Forty patients (22 men, 18 women), median age 63.5 years (27-83 years) were treated with FOLFOX 4 or 6. Nine patients had tumours exhibiting high MSI (MSI group) and 31 patients had tumours exhibiting microsatellite stability (MSS group). In the MSS group, 11 partial responses (36%) were observed, while there were only two in the MSI group (22%) (no significant difference). The two patients who were responders in the MSI group were treated with FOLFOX 6. The overall survival was not significantly different for MSI and MSS patients. CONCLUSION: No significant differences in the overall response rate or overall survival between the two groups of patients were observed. However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.

Elevated level of p60c-src in virus-transformed murine megakaryocytic cell lines.

Megakaryocytic cell lines derived from mouse bone marrow cells transformed by the Myeloproliferative Leukemia Virus (MPLV) contain elevated levels of p60c-src. Northern blot analysis revealed the presence of a 4 kb normal sized c-src transcript only in MPLV-transformed megakaryocytic cell lines containing a high percentage of acetylcholinesterase positive cells (AChE+ greater than 10%), but not in MPLV-transformed erythroblastic or myeloblastic cell lines. The p60c-src protein was identified in lysates from in vivo labelled cells and in in vitro labelled membrane extracts by immunoblotting analysis and by immunoprecipitations with specific anti-src antibodies. In dimethylsulfoxide (DMSO) treated cells, the number of AChE+ cells increased together with p60c-src kinase activity indicating a possible correlation between p60c-src expression/activity and megakaryocytic differentiation.

Birth weight and blood pressure in young adults: a prospective twin study.

BACKGROUND: The intrauterine environment may be a critical period for the development of hypertension in later life. In the present study, we applied the twin approach to estimate the contribution of genetic and environmental causes that may underlie the birth weight-adult blood pressure association. METHODS AND RESULTS: Birth weights of 418 twin pairs were obtained prospectively, and resting and 24-hour ambulatory blood pressures were obtained at the age of 18 to 34 years. In women, resting systolic blood pressure decreased 4.27 mm Hg (P<0.001) and diastolic pressure decreased 2.18 mm Hg (P=0.02) per kilogram increase in birth weight. Similar associations were found for ambulatory measurements, although these were somewhat less pronounced. Pair-wise analysis confirmed these findings: twin pairs of whom both members had a low birth weight (<2500 g) had a higher systolic blood pressure compared with twins who both had a high birth weight (>/=2500 g). Systolic blood pressure of the lightest of a low-birth-weight pair was >/=4.7 mm Hg (P=0.02) higher and of the heaviest >/=2.4 mm Hg higher (P=0.2) than similar measurements in high-birth-weight pairs. Intrapair differences in blood pressure between the lightest and the heaviest at birth were only present in low-birth-weight pairs. The results were similar for monozygotic and dizygotic twin pairs. In men, no associations were found between birth weight and adult blood pressure. CONCLUSIONS: These findings suggest that prenatal programming of adult blood pressure occurs at least in female twins. We suggest that particularly maternal influences, experienced by both twin members, may underlie the association between birth weight and blood pressure. The fetoplacental unit seems to influence blood pressure only when both fetuses had low birth weight.

Peak oxygen uptake better predicts outcome than submaximal respiratory data in heart transplant candidates.

BACKGROUND: Many studies have focused on the prognostic power of peak oxygen uptake VO(2) in patients with chronic heart failure, but maximal exercise testing is not without risk. The purpose of the present study was, therefore, to assess the prognostic significance of the steepness of changes in ventilation and carbon dioxide output VO(2) during submaximal exercise in comparison with VO(2). METHODS AND RESULTS: The study population consisted of 284 adult heart transplant candidates who performed a graded maximal bicycle ergometer test with respiratory gas analysis. Using the respiratory data up to a gas exchange ratio of 1.0, 3 submaximal slopes were calculated in each patient. During follow-up (median, 1.33 years), 57 patients died and 149 had >/=1 cardiovascular event. When using Cox proportional hazards analysis, both peak VO(2) and submaximal respiratory slopes predicted outcome before and after accounting for age, sex, and body mass index. However, whereas the prognostic power of peak VO(2) was independent of submaximal respiratory data, the prognostic significance of the slopes was lost after controlling for peak VO(2). Stepwise regression analysis even selected peak VO(2) as an independent prognostic index among the following factors: cause of heart failure, ejection fraction, pulmonary vascular resistance, natremia, and the forced expiratory volume in 1 s. CONCLUSIONS: Respiratory data during submaximal exercise are significant predictors of outcome in patients with chronic heart failure, but their prognostic power is inferior to that of peak VO(2). However, these data may be useful when maximal exercise is contraindicated or not achievable.

Identification of risk factors in hypertensive patients: contribution of randomized controlled trials through an individual patient database.

BACKGROUND: Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. METHODS AND RESULTS: Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor. CONCLUSIONS: Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.

Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. METHODS AND RESULTS: Patients who were >/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (>/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. CONCLUSIONS: Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.

Left ventricular dynamics during exercise in elite marathon runners.

To assess left ventricular structure and function at rest and during exercise in endurance athletes, 10 elite marathon runners, aged 28 to 37 years, and 10 matched nonathletes were studied by echocardiography and supine bicycle ergometry. Each athlete's best marathon time was less than 2 h 16 min. Echocardiography was performed at rest, at a 60 W work load and at an individually adjusted work load, at which heart rate was 110 beats/min (physical working capacity 110 [PWC110]). Oxygen uptake at PWC110 averaged (+/- SD) 1.14 +/- 0.2 liters/min in the nonathletes and 2.0 +/- 0.2 liters/min in the runners (p less than 0.001). The left ventricular internal diameter at end-diastole was similar at the three activity levels in the control subjects but increased significantly from rest to exercise in the runners (p less than 0.001). Left ventricular systolic meridional wall stress remained unchanged during exercise in the nonathletes but was significantly higher at PWC110 in the athletes (p less than 0.05). Both the systolic peak velocity of posterior wall endocardial displacement and fractional shortening of the left ventricular internal diameter increased with exercise; at PWC110 the endocardial peak velocity was higher in the runners than in the control subjects (p less than 0.01). The endocardial peak velocity during relaxation was comparable in athletes and control subjects at rest, increased similarly at a 60 W work load, but was higher in the runners at PWC110 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The pulse pressure-to-stroke index ratio predicts cardiovascular events and death in uncomplicated hypertension.

OBJECTIVES: The goal of this study was to assess the prognostic power of the pulse pressure-to-stroke index (PP-to-SVi) ratio for cardiovascular events and mortality in patients with uncomplicated hypertension. BACKGROUND: The prognostic significance of pulse pressure (PP) has been studied repeatedly, but few data are available on the PP-to-SVi ratio. METHODS: Invasive hemodynamic measurements, including brachial intra-arterial pressure and stroke index by the direct oxygen Fick method, were performed in the period 1972 to 1982 in 192 patients with uncomplicated hypertension; their outcome was ascertained in 1994. RESULTS: Age at baseline averaged 37 +/- 12 years; brachial artery pressure was 165 mm Hg +/- 30/89 +/- 17 mm Hg; PP averaged 76 mm Hg +/- 18 mm Hg, and the PP-to-SVi ratio was 1.67 mm Hg/(ml/m2) +/- 0.73 mm Hg/(ml/m2). During 3,057 patient years of follow-up, 19 patients died, and 44 experienced at least one fatal or nonfatal cardiovascular event. Cox regression analysis revealed that the PP-to-SVi ratio was a significant predictor of fatal and nonfatal cardiovascular events and of all-cause mortality after control for age and gender (p < 0.01). Its predictive power persisted after additional adjustment for mean arterial pressure and heart rate. Each 0.75-mm Hg/(ml/m2) increase in the PP-to-SVi ratio was independently associated with a 79% increase in the risk of a cardiovascular event (p = 0.01) and a 2.05-fold greater risk of all-cause mortality (p = 0.01). CONCLUSIONS: The PP-to-SVi ratio is a significant and independent predictor of cardiovascular events and mortality in selected patients with uncomplicated hypertension.

Assessment of stiffness of the hypertrophied left ventricle of bicyclists using left ventricular inflow Doppler velocimetry.

Sixteen male bicyclists and 16 control subjects were studied to assess whether the left ventricular hypertrophy of athletes is associated with changes in diastolic left ventricular function. The cyclists had a larger left ventricular internal diameter on echocardiography (55.2 versus 47.9 mm; p less than 0.001) and a disproportionate increase in wall thickness relative to the internal diameter (0.48 versus 0.41; p less than 0.01), indicating a mixed eccentric-concentric type of hypertrophy. Left ventricular inflow Doppler velocimetry showed similar results in athletes and control subjects for peak flow velocities in the atrial contraction phase (30 versus 32 cm/s; p = NS) and in the early diastolic rapid filling phase (71 versus 67 cm/s; p = NS). The similar ratio of both velocities, that is, 0.43 in the cyclists and 0.49 in the control subjects, suggests that left ventricular distensibility is unaltered in cyclists. It is concluded that the left ventricular hypertrophy observed in cyclists is not associated with changes in ventricular stiffness, as estimated from left ventricular inflow Doppler velocimetry.

Prognostic significance of peak exercise capacity in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to investigate the prognostic significance of peak oxygen uptake in patients with coronary artery disease who had an exercise test that could be sustained to exhaustion without limiting symptoms. BACKGROUND: Many studies have reported an inverse association between the level of exercise reached during a stress test and mortality or cardiovascular morbidity. These studies have used submaximal or symptom-limited exercise testing in patients with a recent myocardial infarction. METHODS: Peak oxygen uptake was measured in male patients > or = 4 weeks after myocardial infarction (312 patients) or coronary artery surgery (215 patients) by use of a graded uninterrupted exercise test performed to exhaustion. Apart from peak oxygen uptake, several risk factors for cardiovascular disease, patient and exercise characteristics and drug treatment were considered in the Cox proportional hazards model. RESULTS: During the total follow-up period of 3,213 patient-years, 53 patients died. Of these 53 patients, 33 died of cardiovascular causes. All-cause and cardiovascular mortality decreased with increasing peak oxygen uptake, even after adjustment for significant covariates. The relative hazard rates of 0.43 and 0.29 indicate that a hypothetic increase in peak oxygen uptake by 1 liter/min could be associated with decreases in all-cause and cardiovascular mortality of 57% and 71%, respectively. CONCLUSIONS: Exercise capacity is an independent predictor for subsequent all-cause and cardiovascular mortality in patients able to perform an exercise test until exhaustion.

Electrocardiographic changes after physical training in patients with myocardial infarction.

Electrocardiographic voltage measurements were performed in 24 men with an inferior myocardial infarction before and after 14 +/- 0.5 weeks of physical training. Oxygen uptake at peak exercise increased 42% and heart rate at rest was significantly decreased after training. Increases were found in the magnitude of the R waves in leads II, aVF and V4 to V6; of the S wave in leads V1 and V3; of the T waves in V5 and V6; and of the Sokolow index of QRS voltage. Also, the magnitude of the mean electrical vector in the frontal plane was significantly higher after training. These data were compared with those derived from two electrocardiographic tracings, separated by an average of 19 +/- 1.5 weeks, of 20 other patients with an inferior myocardial infarction who were comparable in age, weight, risk factor and delay between infarction and first examination, but who were not trained. When the electrocardiographic changes between the two observations were compared for the two groups, the trained patients show significant increases in the magnitude of the R wave in the left precordial leads, and leads II and aVF and the Sokolow voltage criterion; in the magnitude of the T wave in leads V5 and V6; and in the magnitude of the mean electrical vector in the frontal plane. It is concluded that physical training in patients with myocardial infarction can alter cardiac structure, as evaluated by voltage measurements on the electrocardiogram.