Changes In Rate-pressure Product Research Articles

Changes in rate-pressure product associated with pregnancy

In nonpregnant individuals, the rate-pressure product, the product of heart rate and systolic blood pressure, is used as a noninvasive surrogate of myocardial O2 consumption during cardiac stress testing. Pregnancy is considered a physiological cardiovascular stress test. Evidence describing the impact of pregnancy on myocardial O2 demand, as assessed by the rate-pressure product, is limited. This study aimed to describe changes in the rate-pressure product for each pregnancy trimester, during labor and delivery, and the postpartum period among low-risk pregnancies. This was a retrospective cohort study that assessed uncomplicated pregnancies delivered vaginally at term. We collected rate-pressure product (heart rate × systolic blood pressure) values preconception, during pregnancy for each trimester (at ≤13 weeks + 6/7 days, at 14 weeks + 0/7 days through 27 weeks + 6/7 days, and at ≥28 weeks + 0/7 days), during the labor and delivery encounter (hospital admission until complete cervical dilation, complete cervical dilation until placental delivery, and after placental delivery until hospital discharge), and during the outpatient postpartum visit at 2 to 6 weeks after delivery. We calculated the percentage change at each time point from the preconception rate-pressure product (delta rate-pressure product). We used a mixed-linear model to analyze differences in the mean delta rate-pressure product over time and the influence of prepregnancy age, prepregnancy body mass index, and neuraxial anesthesia status during labor and delivery on these estimates. Our cohort comprised 316 patients. The mean rate-pressure product increased significantly from preconception starting at the third trimester of pregnancy and during labor and delivery (P≤.05). The mean delta rate-pressure product peaked at 12% and 38% in the third trimester and during labor and delivery, respectively. Prepregnancy body mass index was inversely correlated with the mean delta rate-pressure product changes (estimate, -0.308; 95% confidence interval, -0.536 to -0.80; P=.008). In contrast, neither the prepregnancy age, nor neuraxial anesthesia status during labor had a significant influence on this parameter. This study validates the transient but significant increase in the rate-pressure product, a clinical estimate of myocardial O2 demand, during uncomplicated pregnancies delivered vaginally at term. Pregnant individuals with lower prepregnancy body mass index experienced a sharper increase in this parameter. Patients who receive neuraxial anesthesia during labor and delivery experience similar changes in the rate-pressure product as those who did not.

Comparison Between 6 Minutes Walking Distance (6MWD), Changes in Rate Pressure Product (RPP) and Heart Rate Walking Speed Index (HRWSI) of 6 Minutes Walk Test (6MWT) Pre-Discharge as a Predictor Major Adverse Cardiac Event (MACE) in Patients with Acute Heart Failure

Background: Heart failure (HF) is a significant cause of morbidity and mortality worldwide in middle-aged and older adults. A simple 6MWT assay can provide useful information noninvasively for risk stratification and patient prognosis. A potential parameter is incorporating pulse and blood pressure values ​​into RPP and pulse rate with WS into HRWSI. It is easy to assess the risk of rehospitalization and mortality in HF patients and can be compared with conventional predictors and predictors with expensive biomarker examinations. Aims: To determine the role and comparison of 6MWD, RPP changes and HRWSI in patients with acute heart failure outcomes. Methods: This study was conducted with a prospective observational cohort design. This study is a collaborative study to determine whether 6MWD, changes in RPP and HRWSI at 6MWT pre-discharge can predict MACE events within 90 days after hospital discharge in patients with AHF. Result: The AUC value of 6WMD was 0.338, with a cut-off of 251.0 meters. The sensitivity and specificity of 6MWD were 72% and 63.5%. The AUC value of RPP changes was 0.692 with a cut point 3139.5. The sensitivity and specificity of RPP changes for MACE prediction were 90.0% and 48.0%. HRWSI AUC value was 0.721, with a cut-off of 22.66. The sensitivity and specificity of HRWSI was 80.0% and 64.0%. Low 6MWD had a survival of 54.6%, while patients with GJA who had high 6MWD had an 84.6% survival. Low RPP changes had a survival of 92.3%, and patients with high RPP changes had a survival of 58.8%. Low HRWSI had 88.9% survival, and patients with high RPP changes had 52.5% survival. Conclusion: 6MWD, changes in RPP and HRWSI of 6MWT are potential predictors for MACE within 90 days post hospital discharge in patients with acute heart failure.

Abstract 13149: Mental Stress-Induced Hemodynamic Changes and Cardiovascular Outcomes

Introduction: Hemodynamic responses to mental stress (MS) have been associated with adverse CV outcomes. We investigated if hemodynamic responses during laboratory MS testing are predictive of outcomes. Hypothesis: Lower rate pressure product (RPP) changes during MS testing are predictive of adverse CV events. Methods: Patients recruited into the Mental Stress Ischemia Prognosis Study and Myocardial Infarction and Mental Stress Study 2 studies underwent MS testing with a standardized public speaking stressor and followed for incident CV death, MI rates (primary endpoint) and heart failure hospitalizations (secondary endpoint). Maximum changes in the RPP during MS were calculated. A generalized linear mixed model determined predictors of RPP change, and Prentice, Williams, Peterson model gap time approach was used for analysis of recurrent events after adjustment for demographic and clinical variables. Results: In 919 patients (mean 59.6 years; 65.6% men), the median change in RPP was 5,112 mmHg x beats/minute (IQR, 3,666 - 7,120). Patients with lower RPP changes (<median) during MS were more likely to have a lower resting RPP, be male, and have a history of smoking, obesity, and heart failure. Serum epinephrine levels (22.5 ± 37.3 pg/mL; p<0.001) increased after MS and correlated with RPP changes (r = 0.32; p < 0.001). During a mean follow-up of 4.6 years, there were 135 CV death and MI events (3.2/100 patient-years) and 279 events including HF hospitalizations (6.7 events/100 patient-years). After adjusting for the baseline RPP, demographics, clinical factors, and medication, patients with lower change in RPP during MS had higher primary [HR, 1.7 (95% CI, 1.1 - 2.5); p = 0.009] and secondary events [HR, 1.5 (95% CI, 1.1 - 2.0); p = 0.006]. Conclusions: A reduced change in RPP during MS is independently associated with worse outcomes in patients with CAD. Whether hemodynamic reactivity during MS can be clinically used to identify residual risk needs further evaluation.

Myocardial blood flow during passive heat exposure in healthy young adults

INTRODUCTION Extreme heat events, such as heatwaves, are associated with a greater risk of cardiovascular mortality. However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. Upon exposure to a hot environment, cardiac contractility and heart rate increase thereby presumably increasing myocardial metabolism. Although greater oxygen extraction contributes, an increase in myocardial metabolism is primarily met by greater myocardial blood flow. It is therefore conceivable that the required myocardial blood flow during heat exposure exceeds the capacity for myocardial blood flow to increase in vulnerable individuals. However, the extent to which myocardial blood flow increases during heat exposure is unknown. The purpose of this study is to test the hypothesis that passive heat exposure increases myocardial blood flow. METHODS Five healthy adults (31 ± 3 years, 2 women/3 men) participated in 1 experimental visit during which myocardial blood flow was measured by positron emission computed/tomography. Measurements were performed at baseline and during passive heat stress (water-perfused suit with water at 50°C) at an increase in core (rectal) temperature of 0.5°C, 1.0°C, and 1.5°C. Heart rate and rhythm (ECG) and blood pressure (automated auscultation) were also measured. RESULTS Relative to baseline, rate pressure product was greater at an increase in rectal temperature of 0.5°C (+4165 ± 623 bpm × mmHg, p=0.01), 1.0°C (+5015 ± 519 bpm × mm Hg, p<0.01) and 1.5°C (+7516 ± 261 bpm × mm Hg, p<0.01). The increase in rate pressure product was primarily due to an increase in heart rate (p<0.01), as systolic blood pressure was not affected by heat exposure (p=0.12). Relative to baseline values, myocardial blood flow increased at an increase in rectal temperature of 0.5°C (+0.45 ± 0.09 mL/min/g, p=0.03), 1.0°C (+0.61 ± 0.06 mL/min/g, p<0.01) and 1.5°C (+1.10 ± 0.22 mL/min/g, p=0.02). Overall, myocardial blood flow increased 2.7 ± 1.0-fold relative to baseline at an increase in rectal temperature of 1.5°C. The change in myocardial blood flow during heat exposure correlated with the change in rate pressure product (r=0.78, p<0.01). CONCLUSION These results suggest that passive heat exposure increases myocardial blood flow in proportion with the increase in rate pressure product in young healthy adults.

A study on the effect of manual hyperinflation on oxygenation and hemodynamic parameters in mechanically ventilated patients after valve replacement surgery

BACKGROUND: Valve replacement surgeries being a major surgery require general anesthesia. Patients are kept on mechanical ventilation postoperatively which can cause some major dysfunctions of the respiratory and circulatory systems of the human body. Manual hyperinflation (MHI) is a technique that provides a tidal volume greater than the baseline volume and produces a turbulent flow that brings benefits such as improvement of static compliance of the respiratory system, increased oxygenation, mobilization of secretions, and recruitment of collapsed areas of the lung. OBJECTIVES: The aim of this study was to compare the effectiveness of MHI in valve replacement patients on mechanical ventilation in terms of SpO2, heart rate (HR), respiratory rate (RR), blood pressure (BP), mean arterial pressure (MAP), and rate pressure product (RPP). MATERIALS AND METHODS: Thirty cardiothoracic intensive care unit patients who were intubated and mechanically ventilated after valve replacement surgery were given 3–4 MHI breaths with an O2 flow rate of 15 L/min for 6–8 sets or till secretions were heard. Means of the pretreatment and posttreatment values were calculated and compared by the paired t-test. Results: The results from the statistical analysis show that SpO2 remained almost same (P = 0.499). However, heart rate increased significantly (P = 0.048) after MHI. There was no adverse change in RPP (P = 0.409), but BP (P = 0.00 and 0.006), RR (P = 0.000), and MAP decreased significantly (P = 0.0005). CONCLUSION: The MHI technique seems to promote more improvement in hemodynamic parameters than in oxygenation.

Rate pressure product and the components of heart rate and systolic blood pressure in hospitalized heart failure patients with preserved ejection fraction: Insights from ASCEND-HF.

Heart rate and systolic blood pressure (SBP) are prognostic markers in heart failure (HF) with reduced ejection fraction (HFrEF). Their combination in rate pressure product (RPP) as well as their role in heart failure with preserved ejection fraction (HFpEF) remains unclear. RPP and its components are associated with HFpEF outcomes. We performed an analysis of Acute Study of Clinical Effectiveness of Nesiritide in Subjects With Decompensated Heart Failure (ASCEND-HF; http://www.clinicaltrials.gov NCT00475852), which studied 7141 patients with acute HF. HFpEF was defined as left ventricular ejection fraction ≥40%. Outcomes were assessed by baseline heart rate, SBP, and RPP, as well as the change of these variables using adjusted Cox models. After multivariable adjustment, in-hospital change but not baseline heart rate, SBP, and RPP were associated with 30-day mortality/HF hospitalization (hazard ratio [HR]: 1.17 per 5-bpm heart rate, HR: 1.20 per 10-mm Hg SBP, and HR: 1.02 per 100 bpm × mm Hg RPP; all P < 0.05). Baseline SBP was associated with 180-day mortality (HR: 0.88 per 10-mm Hg, P = 0.028). Though change in RPP was associated with 30-day mortality/HF hospitalization, the RPP baseline variable did not provide additional associative information with regard to outcomes when compared with assessment of baseline heart rate and SBP variables alone. An increase in heart rate and SBP from baseline to discharge was associated with increased 30-day mortality/HF hospitalization in HFpEF patients with acute exacerbation. These findings suggest value in monitoring the trend of vital signs during HFpEF hospitalization.

Peripheral revascularization attenuates the exercise pressor reflex and increases coronary exercise hyperemia in peripheral arterial disease.

Peripheral arterial disease (PAD) is associated with augmented blood pressure (BP) and impaired coronary blood flow responses to exercise, which may increase cardiovascular risk. We investigated the effects of leg revascularization on the BP and coronary blood flow responses to exercise in PAD. Seventeen PAD patients (11 men, 66 ± 2 yr) performed single-leg plantar flexion exercise 24 h before and 1 mo following leg revascularization. BP and heart rate (HR) were measured continuously, and rate pressure product (systolic BP × HR) was calculated as an index of myocardial oxygen demand. Coronary blood velocity was obtained by transthoracic Doppler echocardiography in 8/17 subjects. The mean BP response to plantar flexion exercise was attenuated by leg revascularization (pre-revascularization: 15 ± 4 vs. post-revascularization: 7 ± 3 mmHg, P = 0.025). The HR response to plantar flexion was also attenuated following leg revascularization (pre-revascularization: 9 ± 1 vs. post-revascularization: 6 ± 1 beats/min, P = 0.006). The change in coronary blood velocity with exercise was greater at the post-revascularization visit: 4 ± 1 vs. pre-revascularization: -1 ± 2 cm/s ( P = 0.038), even though the change in rate pressure product was not greater following revascularization in these subjects (pre-revascularization: 2,796 ± 871 vs. post-revascularization: 1,766 ± 378 mmHg·beats/min, P = 0.082). These data suggest that leg revascularization alters reflex control of BP, HR, and coronary blood flow in response to exercise in patients with PAD. NEW & NOTEWORTHY We found that peripheral revascularization procedures lowered exercise blood pressure and improved coronary blood flow in patients with peripheral arterial disease.

Efficacy of spinal cord stimulation as an adjunct therapy for chronic refractory angina pectoris

IntroductionPatients with chronic refractory angina whose symptoms are not controlled with conventional therapies have a poor quality of life. Adjunctive therapies, such as spinal cord stimulation (SCS) may be considered in these cases. We sought to examine whether SCS is associated with changes in exercise capacity and angina severity in these patients. MethodsWe searched Pubmed, Medline and other databases until December 2015. Two reviewers independently extracted data and assessed risk of bias. Exercise capacity included exercise duration and rate pressure product, determined via an exercise test. Angina severity included daily angina frequency and nitrate consumption. ResultsA total of 518 participants (1048.25 person-years of follow-up), from 14 studies met our inclusion criteria. The mean age was 66.8years and 68.5% were men. SCS implant duration ranged from 3weeks to 5years (median: 6months). Using random effects meta-analysis, we found that SCS was associated with a higher exercise duration (1.90min, 95% CI 1.71, 2.06) and lower angina severity, 1.55 less daily angina episodes, (95% CI −1.75, −1.33), 1.54 less daily nitrates consumed, (95% CI −1.81, −1.26), and a 22 points higher SF-36 angina frequency score (95% CI 10.76, 32.81; p<0.0001) on follow-up. The change in rate pressure product was not significant. ConclusionThis meta-analysis suggests that SCS, as an adjunct therapy to medical management, may be associated with a longer exercise duration and lower angina frequency and nitrate consumption in patients with chronic refractory angina pectoris who are not candidates for percutaneous intervention or revascularization.

Coronary Blood Flow Regulation is Impaired During Exercise in Patients with Peripheral Arterial Disease

Peripheral arterial disease (PAD) is associated with an augmented blood pressure response while walking, impaired vascular function, and increased risk of myocardial infarction. We hypothesized that coronary exercise hyperemia is impaired in PAD. Seven PAD patients (67± 2 yrs) and 11 healthy controls (64 ± 2 yrs) performed dynamic plantar flexion exercise at progressive workloads (0.5 ‐ 7.0 kg) with their most symptomatic leg. Coronary blood flow velocity (CBV) in the left anterior descending artery was measured by transthoracic Doppler echocardiography and blood pressure and heart rate were monitored continuously. Rate Pressure Product (RPP) and the myocardial O2 supply/demand ratio (CBV/RPP *1000) were calculated. Since PAD patients exercised for a shorter duration, data were compared at the 2.0 kg workload, which all subjects performed with minimal pain. The change in RPP from rest to exercise at 2.0 kg was augmented in PAD patients vs. controls (2417 ± 489 vs. 1026 ± 143 mmHg*bpm, P = 0.01). The change in the myocardial O2 supply/demand ratio from rest to exercise was impaired in PAD patients vs. controls (2.94 ± 0.99 vs. 5.17 ± 1.35 au, P = 0.05). These data suggest that coronary hyperemia is inadequate for the large rise in myocardial metabolism during low intensity exercise in PAD, which may increase risk for adverse cardiovascular events.

Design and rationale for the randomised, double-blinded, placebo-controlled Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS) crossover study.

BackgroundGlucagon-like peptide-1 is an incretin hormone essential for normal human glucose homeostasis. Expression of the glucagon-like peptide-1 receptor in the myocardium has fuelled growing interest in the direct and indirect cardiovascular effects of native glucagon-like peptide-1, its degradation product glucagon-like peptide-1(9-36), and the synthetic glucagon-like peptide-1 receptor agonists. Preclinical studies have demonstrated cardioprotective actions of all three compounds in the setting of experimental myocardial infarction and left ventricular systolic dysfunction. This has led to Phase 2 trials of native glucagon-like peptide-1 and incretin-based therapies in humans with and without Type 2 diabetes mellitus. These studies have demonstrated the ability of glucagon-like peptide-1, independent of glycaemic control, to positively modulate the metabolic and haemodynamic parameters of individuals with coronary artery disease and left ventricular systolic dysfunction. We aim to add to this growing body of evidence by studying the effect of chronic glucagon-like peptide-1 receptor activation on exercise-induced ischaemia in patients with chronic stable angina managed conservatively or awaiting revascularisation. The hypothesis being liraglutide, a subcutaneously injectable glucagon-like peptide-1 receptor agonist, is able to improve exercise haemodynamics in patients with obstructive coronary artery disease when compared with saline placebo.Methods and designThe Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS) trial is an investigator-initiated single-centre randomised double-blinded placebo-controlled crossover proof-of-principle physiological study. Primary endpoints are change in rate pressure product at 0.1 mV ST-segment depression and change in degree of ST-segment depression at peak exercise during sequential exercise tolerance testing performed over a 6-week study period in which 26 patients will be randomised to either liraglutide or saline with crossover to the opposing regimen at week 3.DiscussionThe study will be conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The local Research Ethics Committee and Medicines and Healthcare Products Regulatory Agency have approved the study.Trial registrationNational Institute of Health Research Clinical Research Network (NIHR CRN) Portfolio ID 11112 and ClinicalTrials.gov Identifier NCT02315001.

Coronary responses to cold air inhalation following afferent and efferent blockade.

Cardiac ischemia and angina pectoris are commonly experienced during exertion in a cold environment. In the current study we tested the hypotheses that oropharyngeal afferent blockade (i.e., local anesthesia of the upper airway with lidocaine) as well as systemic β-adrenergic receptor blockade (i.e., intravenous propranolol) would improve the balance between myocardial oxygen supply and demand in response to the combined stimulus of cold air inhalation (-15 to -30°C) and isometric handgrip exercise (Cold + Grip). Young healthy subjects underwent Cold + Grip following lidocaine, propranolol, and control (no drug). Heart rate, blood pressure, and coronary blood flow velocity (CBV, from Doppler echocardiography) were continuously measured. Rate-pressure product (RPP) was calculated, and changes from baseline were compared between treatments. The change in RPP at the end of Cold + Grip was not different between lidocaine (2,441 ± 376) and control conditions (3,159 ± 626); CBV responses were also not different between treatments. With propranolol, heart rate (8 ± 1 vs. 14 ± 3 beats/min) and RPP responses to Cold + Grip were significantly attenuated. However, at peak exercise propranolol also resulted in a smaller ΔCBV (1.4 ± 0.8 vs. 5.3 ± 1.4 cm/s, P = 0.035), such that the relationship between coronary flow and cardiac metabolism was impaired under propranolol (0.43 ± 0.37 vs. 2.1 ± 0.63 arbitrary units). These data suggest that cold air breathing and isometric exercise significantly influence efferent control of coronary blood flow. Additionally, β-adrenergic vasodilation may play a significant role in coronary regulation during exercise.

Contribution of sympathetic activation to coronary vasodilatation during the cold pressor test in healthy men: effect of ageing

The sympathetic nervous system is an important regulator of coronary blood flow. The cold pressor test (CPT) is a powerful sympathoexcitatory stressor. We tested the hypotheses that: (1) CPT-induced sympathetic activation elicits coronary vasodilatation in young adults that is impaired with advancing age and (2) combined α- and β-adrenergic blockade diminishes/abolishes these age-related differences. Vascular responses of the left anterior descending artery to the CPT were determined by transthoracic Doppler echocardiography before (pre-blockade) and during (post-blockade) systemic co-administration of α- and β-adrenergic antagonists in young (n = 9; 26 ± 1 years old, mean ± SEM) and older healthy men (n = 9; 66 ± 2 years old). Coronary vascular resistance (CVR; mean arterial pressure/coronary blood velocity) was used as an index of vascular tone. CPT decreased CVR (i.e. coronary vasodilatation occurred) in young ( -33 ± 6%), but not older men ( -3 ± 4%; P < 0.05 vs. young) pre-blockade. Adrenergic blockade abolished CPT-induced coronary vasodilatation in young men ( -33 ± 6% vs. 0 ± 6%, pre-blockade vs. post-blockade, respectively; P < 0.05) such that responses post-blockade mirrored those of older men ( -3 ± 4% vs. 8 ± 9%; both P > 0.05 compared to young pre-blockade). Impaired CPT-induced coronary vasodilatation could not be explained by a reduced stimulus for vasodilatation as group and condition effects persisted when CVR responses were expressed relative to myocardial oxygen demand (rate-pressure product). These data indicate that the normal coronary vascular response to sympathetic activation in young men is pronounced vasodilatation and this effect is lost with age as the result of an adrenergic mechanism. These findings may help explain how acute sympathoexcitation may precipitate angina and coronary ischaemic events, particularly in older adults.

Myocardial oxidative metabolism is increased due to haemodynamic overload in patients with aortic valve stenosis: assessment using 11C-acetate positron emission tomography

The relationship between myocardial oxidative metabolism and pressure overload in aortic valve stenosis (AS) is not fully elucidated. We identified the determinants of myocardial oxidative metabolism by measuring its changes after aortic valve replacement (AVR) in patients with AS. Myocardial 11C-acetate clearance rate constant (Kmono), an index of oxidative metabolism, was measured non-invasively by using positron emission tomography in 16 patients with moderate to severe AS and 7 healthy controls. The severity of AS was assessed by echocardiography. Of 16 patients, 5 were reexamined at 1 month after AVR. Kmono was significantly higher in patients with AS than healthy controls by 42% (0.068±0.014 vs 0.048±0.007/min, p<0.01). Kmono was significantly correlated with age (r=0.58, p<0.01), left ventricular (LV) mass index (r=0.61, p<0.01) and estimated systolic LV pressure (r=0.81, p<0.001) measured by echocardiography. By multivariate analysis, estimated LV systolic pressure was an independent predictor of Kmono (β=0.93, p<0.01). After AVR, Kmono (from 0.075±0.012 to 0.061±0.014/min, p=0.043) and LV mass index (from 183±49 to 124±41 g/ml2, p=0.043) were significantly decreased despite no significant changes in rate-pressure product. Myocardial oxygen metabolism was increased in patients with AS, which was decreased after AVR. The increased myocardial oxidative metabolism in AS was largely attributable to the pressure overload of the LV.

Effect of pyruvate, lactate and insulin on ATP supply and demand in unpaced perfused rat heart

Mitochondrial respiration/oxidative phosphorylation is the main source of energy, in the form of ATP, in the heart under physiological conditions. Different respiratory substrates were used in various experiments during heart perfusion: glucose, pyruvate, lactate, glucose+pyruvate, glucose+lactate, glucose+insulin etc. Also under physiological conditions, the concentration of respiratory substrates/hormones in blood can vary significantly. In the present study, we tested the effect of pyruvate, lactate and insulin (all in the presence of glucose) and glucose (in the presence of pyruvate) on the ATP-producing and -consuming blocks in perfused rat heart, in a system where HR (heart rate) was allowed to vary (no pacing). Changes in RPP (rate-pressure product) and PCr (phosphocreatine) concentration were measured. PAA (Proportional Activation Approach) was used to visualize and quantitatively analyse the data. It was demonstrated that addition of glucose (in the presence of pyruvate) exerted essentially no effect on the system. Insulin (in the presence of glucose) activated only the ATP producer. The most interesting finding is that, in our system, pyruvate and lactate (added in the presence or instead of glucose) activated ATP producer, but significantly inhibited ATP consumer (their effect was quantitatively identical).

Circadian Variation In The Reactivity Of The Rate-pressure Product To Everyday Physical Activities In Hypertensive Patients

It has been suggested that the exercise-related response of the rate-pressure product (RPP) is a prognostic marker of cardiovascular mortality. Given that out-of-hospital sudden cardiac events are more common in the morning and, to a lesser extent, in the late afternoon, it is pertinent to examine whether RPP and its reactivity to physical activity vary with time of day. PURPOSE: To use a novel RPP 'reactivity index' to investigate whether the RPP response to everyday physical activities changes over a normal sleep-wake cycle. METHODS: Two hundred and eighteen male, and 222 female, hypertensive patients (aged 15-81 yrs) underwent 24-h monitoring of systolic blood pressure and heart rate (both recorded every 20 min). Wrist movement was recorded every 10 s and summed over the 15 min that preceded a BP measurement. The product of systolic BP and HR was calculated, and RPP reactivity indices were derived by regressing the change in RPP against the change in activity for twelve 2-h data bins. These indices were then analysed for time-of-day differences using a covariate-controlled general linear model. RESULTS: The RPP showed circadian variation (P<0.0005), with a peak of 11004 (95%CI = 10757 to 11250) beat.min-1.mmHg occurring at 10:00 h. The reactivity of RPP to physical activity showed two distinct peaks between 08:00-10:00 and between 18:00-20:00 (P<0.0005) which were >3 times greater than the RPP reactivity during the nocturnal period. This circadian variation in RPP reactivity was not moderated by wake-time, medication use, age or gender (P>0.30). CONCLUSION: Under conditions of normal living, the reactivity of the rate-pressure product to a given unit change in physical activity is substantially higher in the morning and early evening compared with other times of day. These times are consistent with the peak times of day for out-of-hospital sudden cardiac events and, therefore, add weight to the notion that the response of the rate-pressure product to exercise could be a useful prognostic marker of cardiovascular mortality.

24-Hour Variation in the Reactivity of Rate-Pressure-Product to Everyday Physical Activity in Patients Attending a Hypertension Clinic

The exercise-related response of the rate-pressure-product (RPP) is a prognostic marker of autonomic imbalance, cardiovascular mortality, and silent myocardial ischemia in hypertension. In view of the well-known 24 h variation in out-of-hospital sudden cardiac events, our aim was to investigate whether the reactivity of RPP to everyday physical activities varies over the 24 h. Ambulatory measurements of systolic blood pressure (BP) and heart rate were recorded every 20 min for 24 h in 440 diurnally active patients attending a hypertension clinic. Wrist activity counts were summed over the 15 min that preceded a BP measurement. An RPP reactivity index was derived for each of twelve 2 h data bins by regressing the change in RPP against the change in logged activity counts. The RPP showed 24 h variation (p < 0.0005), with a peak of 11,004 (95% CI = 10,757 to 11,250) beat · min−1 · mmHg occurring at 10:00 h (2 h after mean wake-time). The overall 24 h mean of RPP reactivity was 477 beat · min−1 · mmHg · logged activity counts−1 (95% CI = 426 to 529). The largest increase in RPP reactivity occurred within the first 2 h after waking (p < 0.0005). There were no subsequent significant differences in RPP reactivity up to 14 h after waking. The lowest RPP reactivity was found 18–20 h after waking, with a peak-to-trough variation of 593 beat · min−1 · mmHg · logged activity counts−1 (95% CI = 394 to 791, p < 0.0005). Although this variation was not moderated by BP status, age, or sex, less variability in RPP reactivity was found for the medicated individuals during the waking hours. These data suggest that under conditions of normal living, the reactivity of RPP to a given change in physical activity increases markedly during the first 2 h after waking from nocturnal sleep, the time when out-of-hospital sudden cardiac events are also most common. Therefore, these data add weight to the notion that reactivity of RPP to physical activity could be a prognostic marker of autonomic imbalance and cardiovascular mortality, although more research is needed to assess the specific prognostic value of 24 h ambulatory measurements of RPP and physical activity.

Nicotine does not compromise resting myocardial blood flow autoregulation in smokers at high cardiovascular risk

Nicotine has been recognized for years as being pharmacologically responsible for the sympathoexcitatory effects of smoking. The effects of nicotine supplementation on myocardial blood flow as assessed by positron emission tomography are, however, unknown. We tested the hypothesis that nicotine substitution could interfere with myocardial blood flow autoregulation at rest in habitual smokers at risk of coronary artery disease. The short-term effect of a 4-mg nicotine tablet on myocardial blood flow was quantified with 13N ammonia positron emission tomography in 12 smokers with high cardiovascular risk (10 males and 2 females; mean age = 58+/-8 years; SCORE risk >5%). Nicotine increased systolic blood pressure from 129+/-7 to 134+/-7 mmHg (p = .03) and heart rate from 67+/-2 to 69+/-2 bpm (p = .04). As a result, nicotine raised the rate-pressure product from 8618+/-622 to 9285+/-627 bpm mmHg (p = .02). Nicotine tended to increase myocardial blood flow in the circumflex artery territory, but this effect failed to reach the level of statistical significance (from 0.56+/-0.06 to 0.63+/-0.03 ml/min/g; p>.15). This trend disappeared when myocardial blood flow was normalized for the rise in the rate-pressure product. Global myocardial perfusion, normalized for the changes in rate-pressure product, remained unchanged from 0.70+/-0.06 at baseline to 0.71+/-0.03 (ml/min/g)/(bpm mmHg) after nicotine. Nicotine supplementation in habitual smokers with high cardiovascular risk increased myocardial work without compromising resting myocardial blood flow autoregulation.

Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans

Response of myocardial blood flow (MBF) to sympathetic stimulation with cold is modulated by endothelium-related factors and is typically altered in the presence of coronary risk factors. Determinants of flow response to cold pressor testing (CPT) in normal volunteers at low risk for CAD remain less well defined, especially relative to baseline conditions such as hemodynamics and MBF, plasma substrate and lipid levels, and total pharmacologically stimulated vasodilator capacity. In 50 normal volunteers (42+/-13 years; 31 women) without coronary risk factors, insulin resistance, or family history of diabetes/premature CAD, MBF was measured with (13)N-ammonia and PET at baseline, during CPT, and during pharmacologic hyperemia. Sympathetic stimulation with CPT raised heart rate and blood pressure and thus MBF (Delta MBF=0.23+/-0.09 ml/min/g). MBF response, defined in absolute flow units as the difference between CPT and baseline, was independent of age, gender, heart rate, and blood pressure and rate-pressure product (RPP) at baseline as well as plasma substrate and lipid levels with the exception of an association with HDL cholesterol (rho=0.40, p=0.005) but depended on the change in RPP from rest (rho=0.33, p=0.019). Finally, changes in coronary vascular resistance in response to CPT were associated with changes in pharmacologic vasodilation (rho=0.56, p<0.0001). MBF response to sympathetic stimulation with cold (NO-mediated endothelium-dependent vasomotion), reflecting the functional state of the coronary endothelium, was independent of gender, age, and resting heart conditions. It was modulated by HDL cholesterol levels, even in healthy volunteers, and also related to pharmacologically stimulated vasodilator capacity at the coronary vascular resistance level.

Ranolazine for the Treatment of Chronic Angina and Potential Use in Other Cardiovascular Conditions

Chronic angina, a condition that impairs quality of life and is associated with decreased life expectancy, affects &6.4 million Americans.1 Current therapies that reduce angina frequency and nitrate consumption and increase the threshold at which demand-induced myocardial ischemic symptoms become evident include drugs (nitrates, β-blockers, calcium antagonists), exercise conditioning, enhanced external counterpulsation, and coronary revascularization.1–3 Several new investigational drugs are being tested for the treatment of chronic angina.4–9 This review will focus on sustained-release ranolazine, a drug that reduces angina symptoms, with a mechanism of action different from that of currently available pharmacological therapies.8–29 Ranolazine was approved on January 27, 2006, in the United States for use in patients with chronic angina who continue to be symptomatic on β-blockers, calcium antagonists, or nitrates. Ranolazine ([(+) N -(2,6-dimethylphenyl)-4(2-hydroxy-3-(2-methoxyphenoxy)-propyl)-1-piperazine acetamide dihydrochloride]) is an active piperazine derivative that was patented in 1986 and is available in an oral and intravenous form (Figure 1). The immediate-release ranolazine (not in current use) had an average terminal elimination half-life ranging from 1.4 to 1.9 hours and a 10-fold peak/trough difference with dosing of 240 to 400 mg 3 times per day.19 Early studies with immediate-release ranolazine provided evidence of antiischemic/antianginal properties in patients with chronic angina without clinically significant changes in heart rate or blood pressure and are reviewed elsewhere.20–24 Unless otherwise stated, the remainder of this review refers to sustained-release ranolazine. Figure 1. Chemical structure and metabolism of ranolazine. Reprinted with permission from J Clin Pharmacol . 2005;45:422–433.17 Ranolazine (Ranexa; CV Therapeutics Inc, Palo Alto, Calif) is manufactured in a sustained-release form that has a prolonged absorption phase with maximal plasma concentrations (Cmax) typically seen 4 to 6 hours after administration. The average terminal elimination half-life is &7 hours after multiple dosing to steady state, and the …

Predicting exercise training outcome from cardiac rehabilitation.

This study was conducted to identify predictors of training effect after 6 months of supervised exercise for cardiac rehabilitation patients. Data at baseline and after 6 months of supervised exercise from 60 patients with coronary artery disease were used for this study. All the patients exercised 3 days per week for 5 to 9 months. Attendance exceeded 70%. The training effect was independently evaluated by the change in rate-pressure product at a 5-metabolic equivalent (MET) workload (RPP5), and the change in estimated peak METs (METPK) during treadmill testing. Baseline variables were examined to identify predictors of change in RPP5 and METPK separately using multiple linear regression. A reduction in RPP5 (-23 +/- 33 bpm x mm Hg x 10(2); P<.0001) and an increase in METPK (2.1 +/- 1.7 METs; P<.0001) were found after training. Baseline fitness was the best predictor of training effect. Inverse relations were found between baseline scores and change scores for RPP5 (r=-0.68; P<.001) and METpk (r=-0.39; P=.002). Beta-blocker status also was useful for predicting change in RPP5. No association was found between training effect and age, revascularization status, or exercise-induced ischemia. Training effect has limited predictability using baseline variables. No baseline patient characteristics other than high initial fitness were related to reduced training effect. Therefore, patients with clinical characteristics similar to those evaluated in this study can achieve a training effect successfully and are eligible for cardiac rehabilitation. The findings of this study support previous research related to this topic.