Blood Pressure Response In Patients Research Articles

Effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system activity and blood pressure response to hydrochlorothiazide

To evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension. Eight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2 -344T/C polymorphism and gender. A total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2 -344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent. In males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.

The importance of blood pressure response to Valsalva maneuver in patients with puhnonary hypertension

Objective To use a simple bedside technique to verify the pathophysiological mechanism of pulmonary hypertension （PH） in different races. Method The Valsalva maneuver （VM） was performed in patients referred to a specialty PH clinic. The blood pressure response of patients to VM was in different fashions. The blood pressure （BP） was measured by using cuff and stethoscope. When the cuff was inflated to 15 mmHg above the systolic pressure, sound could be heard by auscultation during VM and when the cuff was deflated the sound disappeared over 3 heart beats which was considered as abnormal BP response, and less than 3 heart beats defined as normal BP response. The right heart catheterization in patients with PH as a part of the standard evaluation. Results This study included 84 patients with a mean age of （63 ± 16） years. Those with abnormal BP response to VM had higher pulmonary artery wedge pressure （PAWP） [（22.5±6.6） vs. （11.9±4.3） mmHg, P 〈0.0001] and lower pulmonary vascular resistance [（5.8 ± 4.0） vs. （8.1 ± 4.6 ） WU, P = 0.01]. Blood pressure response to VM did not correlate with mean pulmonary artery （PA） pressure [（46.2 ± 9.9） vs. （43.4 ±10.4） mmHg, P =0.20] or cardiac index （both 2.4 ± 0.6 L/min/m^2）. The abnormal BP response to VM had high sensitivity （89.4%）, specificity （86.1%） and accuracy （86.9%） for determining PAWP〉 15 mmHg.Conclusions BP response to Valsalva maneuver provides important information about left heart filling pressures in patients with PH. Key words: Pulmonary hypertension; Hemodynamics; Valsalva maneuver

Prognostic Value of an Exaggerated Exercise Blood Pressure Response in Patients With Diabetes Mellitus and Known or Suspected Coronary Artery Disease

The prognostic value of an exaggerated exercise systolic blood pressure response (EESBPR) remains controversial. Our aim was to assess whether an EESBPR is associated with the long-term outcome in patients with diabetes mellitus and known or suspected coronary artery disease (CAD). From an initial population of 22,262 patients with known or suspected CAD who underwent treadmill exercise electrocardiography or exercise echocardiography at our institution, 2,591 patients with a history of diabetes mellitus were selected for the present study. EESBPR was defined as systolic blood pressure >220 mm Hg during exercise. The end points were all-cause mortality and hard events (ie, death or myocardial infarction). A total of 236 patients (9.1%) developed an EESBPR during the tests. During a mean follow-up of 6.5 +/- 3.9 years, 484 patients died and 646 experienced hard events. The 10-year mortality rate was 16.6% in patients with an EESBPR compared to 30.9% in those without an EESBPR (p <0.001). The 10-year hard event rate was also lower in patients with an EESBPR (23.2% vs 38.9% in patients without an EESBPR; p <0.001). On multivariate analysis, an EESBPR remained independently associated with a lower risk of all-cause mortality (hazard ratio 0.53, 95% confidence interval 0.36 to 0.78, p = 0.001) and hard events (hazard ratio 0.57, 95% confidence interval 0.41 to 0.79; p <0.001). These results remained consistent in the subgroup of patients without a known history of CAD. In conclusion, an EESBPR was associated with improved survival and a lower rate of death or myocardial infarction in patients with diabetes mellitus and known or suspected CAD.

Adenine/cytosine1166 polymorphism of the angiotensin II type 1 receptor gene and the antihypertensive response to angiotensin-converting enzyme inhibitors

Most of the known actions of angiotensin II are mediated by the angiotensin II type 1 receptor (AGT1R). The adenine/cytosine(1166) (A/C(1166)) polymorphism of the AGT1R gene has been shown to be associated with hypertension and hypertension-related diseases. Thus, it may have the potential to predict the blood pressure response of patients with hypertension to angiotensin-converting enzyme inhibitors (ACEIs). To investigate the association between the A/C(1166) polymorphism and the blood pressure response to ACEIs in a hypertensive cohort. After a 2-week, single-blind, placebo run-in period, ACEIs were administered for 6 weeks to 509 hypertensive patients. The polymorphism was determined by PCR followed by restriction enzyme digestion. The AA genotype, AC genotype, and CC genotype were present in 464 (91.2%), 44 (8.6%), and 1 (0.2%) of patients, respectively. As the frequency of the C allele was quite low (0.05), the genotypes were classified according to the presence or absence of the C allele. After 6 weeks of treatment, the systolic blood pressure reductions in patients with the AA genotype and AC + CC genotype were 14.3 +/- 12.6 and 14.1 +/- 12.2 mmHg, respectively (P = 0.908). The diastolic blood pressure reductions in patients with the AA genotype and AC + CC genotype were 8.6 +/- 7.1 and 8.8 +/- 6.9 mmHg, respectively (P = 0.816). There were no differences in the changes in systolic or diastolic blood pressure after treatment among the two genotype groups. The AGT1R A/C(1166) polymorphism does not predict the response to antihypertensive treatment with ACEIs in Chinese hypertensive patients.

Usefulness of Hypertensive Blood Pressure Response During a Single-Stage Exercise Test to Predict Long-Term Outcome in Patients With Peripheral Arterial Disease

The prognostic value of a hypertensive blood pressure (BP) response is still unclear. Therefore, the prognostic value of a hypertensive BP response in patients during single-stage exercise testing for peripheral arterial disease (PAD) on long-term mortality and major adverse cerebrovascular and cardiac events (MACCEs) was investigated. In addition, effects of statin, beta-blocker, and aspirin use in patients with known or suspected PAD were studied. A total of 2,109 patients were enrolled in an observational prospective study from 1993 to 2005. Hypertensive BP response was defined as an increase in systolic BP > or = 55 mm Hg (95(th) percentile within our population) after a single-stage treadmill exercise test. The outcome was obtained by using the civil registries, and a questionnaire about cardiac events was sent to all survivals. Hypertensive BP response was associated with increased risk of long-term mortality (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12 to 1.80) and MACCEs (HR 1.47, 95% CI 1.09 to 1.97). After adjustments for clinical risk factors and propensity score, baseline statin use was associated with reduced risk of long-term mortality (HR 0.59, 95% CI 0.44 to 0.79), and statin, beta-blocker, and aspirin use were associated with reduced risk of MACCEs (HR 0.59, 95% CI 0.43 to 0.81; HR 0.75, 95% CI 0.60 to 0.95; HR 0.73, 95% CI, 0.57 to 0.92, respectively). In conclusion, hypertensive BP response at exercise in patients with known or suspected PAD is an important independent risk factor for all-cause long-term mortality and MACCEs, whereas statin, beta-blocker, and aspirin use were associated with an improved outcome.

Are there interactions between the Gly460Trp α-adducin gene variant and the use of diuretics?

Treatment with a thiazide diuretic is associated with large interindividual differences in blood-pressure reduction. Both environmental and genetic factors might play a role. Several individual polymorphisms have already been studied for association with blood-pressure response in patients treated with diuretics. α-adducin is one of the more extensively studied polymorphisms. Unfortunately, conflicting results have been found in different populations. More research is needed to unravel the possible interactions between diuretics and the α-adducin polymorphism.

Intron-2 conversion polymorphism of the aldosterone synthase gene and the antihypertensive response to angiotensin-converting enzyme inhibitors

Aldosterone controls sodium balance and intravascular volume, and thus helps regulate blood pressure. Secretion of aldosterone is mainly regulated at the level of expression of the aldosterone synthase (CYP11B2) gene. The intron-2 conversion polymorphism of CYP11B2 was suggested to lead to overexpression of the gene, and may therefore have potential to predict the blood pressure response of patients with essential hypertension to angiotensin-converting enzyme inhibitors (ACEIs). To investigate the association between the intron-2 conversion polymorphism and the blood pressure response to ACEIs in a hypertensive cohort. After a 2-week, single-blind, placebo run-in period, ACEIs were administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. The intron-2 conversion polymorphism was examined by polymerase chain reaction. The IwIw genotype was observed in 106 patients (20.8%), the IwIc genotype in 251 patients (49.3%), and the IcIc genotype in 152 patients (29.9%). After 6 weeks of treatment the reductions in diastolic blood pressure were significantly greater in patients carrying IcIc or IwIc compared with IwIw genotypes (9.2 +/- 7.2 or 9.2 +/- 7.1 versus 6.4 +/- 6.6 mmHg, respectively; analysis of variance, P = 0.001). Stepwise multiple regression analysis showed that significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P < 0.001), intron-2 conversion genotype (P = 0.006) and sex (P = 0.030). The intron-2 conversion polymorphism was related to the diastolic blood pressure lowering response in hypertensive patients treated with ACEIs. Interindividual variation in the efficacy of antihypertensive medications may therefore be influenced by genetic factors.

Redefining the ACE-inhibitor dose-response relationship: substantial blood pressure lowering after massive doses

The blood pressure-lowering dose-response relationship for angiotensin converting enzyme (ACE) inhibitors is assumed to flatten at doses higher than those conventionally used in clinical practice. However, existing clinical trial data do not adequately address the haemodynamic effects of high ACE inhibitor dosages. Therefore, we examined the blood pressure responses in patients presenting to hospital following a deliberate ACE inhibitor overdose. The study design was a retrospective case review, and included all patients who presented to our hospital in the past 5 years after an ACE inhibitor overdose. The data collected were heart rate and systemic blood pressure at various times after ingestion and maximum haemodynamic derangement; these were compared to baseline or recovered values. Data from 33 patients (24 men) were evaluated. The median (inter-quartile range, IQR) age of the patients was 49 years (IQR: 42-56 years). The median stated dose ingested was 140 mg (IQR: 60-280 mg), which is 20x (IQR: 7-42) the defined daily dose. The maximum fall in systolic blood pressure was 50 mmHg (IQR: 40-64 mmHg), diastolic blood pressure was 35 mmHg (IQR: 26-43 mmHg) and mean blood pressure was 39 mmHg (IQR: 30-47 mmHg). The observed reduction in blood pressure following an overdose of an ACE inhibitor was greater than anticipated based on data from therapeutic doses. We conclude that a blood pressure-lowering dose-response relationship extends to higher ACE inhibitor doses than those conventionally used in clinical practice.

Increased hypoxic blood pressure response in patients with amyotrophic lateral sclerosis

Objectives: There is evidence of impaired cardiovascular autonomic control and reduced baroreflex sensitivity in patients with amyotrophic lateral sclerosis (ALS). A compromised baroreflex–chemoreflex interaction might result in inadequate responses to chemoreflex activation with progressive hypercapnia and hypoxia and contribute to early fatalities. This study was performed to assess cardiovascular and ventilatory responses to hypercapnic and hypoxic stimulation in ALS patients with impaired baroreflex function. Patients and methods: In 15 ALS patients with previously demonstrated baroreflex dysfunction and in 15 age-matched controls, we compared electrocardiographic RR-interval (RRI), systolic blood pressure (SBP) and minute ventilation (VE) during normal ventilation and during selective progressive hypoxia and hypercapnia. Results: Ventilatory and RRI responses to hypoxic and hypercapnic stimulation as well as SBP responses to hypercapnia did not differ between patients and controls. In contrast, hypoxia induced a significant SBP increase in patients only. Conclusions: The normal ventilatory and RRI responses to chemoreflex activation suggest intact afferent chemoreflex function. The hypertensive response to hypoxia might be due to a compromised interaction with the baroreflex. Avoiding hypoxic episodes might reduce the risk of cardiovascular crisis in ALS patients.

Better blood pressure response in patients with ACE-inhibitor-associated cough

Better blood pressure response in patients with ACE-inhibitor-associated cough

The impact of molecular medicine upon early cardiovascular drug development.

Heart disease remains the leading cause of death and morbidity in the western world despite significant advances in cardiovascular (CVS) therapeutics. Since the 1960s clinical pharmacologists have been very much involved in bringing forward new classes of CVS drugs. This started with the introduction of β-adrenoceptor blockers in the early 1960s and has continued with calcium antagonists, ACE inhibitors and more recently endothelin antagonists. The principles for classical drug design have been based upon interaction with: receptor sites (β-adreno-ceptor blockers), enzymes (thrombolytics and anticoagulants) and ion channels (calcium antagonists, antiarrhythmics). The advent of molecular biology has added a fourth principle for CVS drug development – that of molecular therapeutics. While classical approaches will still provide new CVS drugs (e.g. platelet IIb/IIIa receptor antagonists and directly acting thrombin inhibitors), there is now anticipation that molecular therapeutics will provide a very specific means of intervention thus potentially avoiding some of the problems associated with the non specificity of conventional approaches, e.g. side-effects associated with lack of cardioselectivity with β-adrenoceptor blockers, risk of bleeding with anticoagulants, cough with ACE inhibitors, controversy following retrospective analysis of the use of calcium antagonists. In the broader sense molecular therapeutics includes both gene therapy and oligonucleotide therapy. However the advances in genetic analysis (identification of polymorphisms associated with diseases) mean that there may be a further impact upon drug development – namely the use of known gene polymorphisms to select patient populations at risk. We will review the status of each of these and prospects for the future.

Exercise-induced abnormal blood pressure responses are related to subendocardial ischemia in hypertrophic cardiomyopathy.

We examined by thallium-201 scintigraphy whether exercise-induced abnormal blood pressure response (BPR) is related to myocardial ischemia. Hemodynamic instabilities during exercise in patients with hypertrophic cardiomyopathy (HCM) are considered to be caused by abnormal reflex control of vascular resistance. In 105 patients with HCM, exercise thallium scintigraphy was performed by means of a multistage, symptom-limited bicycle ergometer exercise test. Eighty-eight patients had normal BPR (> or = 25 mm Hg from baseline to peak exercise), and 17 had abnormal BPR (<25 mm Hg). Clinical characteristics including age, the prevalence of obstruction, New York Heart Association functional class and echocardiographic measurements were similar between the two groups. Left ventricular end-diastolic pressure was significantly higher in patients with abnormal BPR than in those with normal BPR (18+/-8 vs. 14+/-5 mm Hg, p < 0.05). Exercise-induced perfusion abnormalities including fixed and reversible perfusion defects, and left ventricular cavity dilatation (LVCD) were identified in 72 (69%) of 105 study patients. Left ventricular cavity dilatation indicates subendocardial hypoperfusion and is a marker of diffuse subendocardial ischemia. The prevalence of fixed or reversible perfusion defects was similar between the two groups. Patients with abnormal BPR had the higher prevalence of LVCD as compared to those with normal BPR (47.1 vs. 10%, p < 0.0002). Multiple logistic regression analysis revealed that LVCD was independently associated with abnormal BPR (odds ratio 3.76, 95% confidence interval 1.61 to 8.76). Exercise-induced abnormal BPRs in patients with HCM are related to subendocardial ischemia during exercise.

Bispectral analysis of the electroencephalogram during induction of anesthesia may predict hemodynamic responses to laryngoscopy and intubation

The use of electroencephalography as a measure of adequacy of anesthesia has achieved limited success. Our purpose was to determine whether the non-linear properties of the electroencephalogram (EEG) as defined by the bispectral index was a better predictor of autonomic responses to endotracheal intubation during opioid-based anesthesia than the linear statistical properties of the EEG formulated by power spectral analysis. Thirty-nine adults scheduled for elective non-cranial surgery had a continuous EEG recorded during induction of anesthesia and endotracheal intubation. Anesthesia consisted of thiopental and nitrous oxide in oxygen, followed by 1 of 5 randomized opioid dose regimens. The EEG was continuously recorded and blood pressure was measured every minute. All electroencephalographic parameters were derived for the 3 min before and after intubation and were compared to the blood pressure and heart rate responses. Responders were defined by 2 analyses: patients who had a 20% or greater increase (1) in blood pressure or (2) in heart rate to laryngoscopy. Responders and non-responders were compared using Student's unpaired t test, and differences due to dose regimens were examined with logistic regression. Based on the criterion for blood pressure change, there were 27 responders and 12 non-responders. Heart rate changes did not differentiate between the two groups. There was a significant difference between response groups as measured by the bispectral index which distinguished responders from non-responders independently of the amount of drug given. None of the variables of power spectral analysis accurately distinguished responder from non-responder. We conclude that the bispectral index of the EEG may accurately predict blood pressure responses in patients undergoing endotracheal intubation after induction of general anesthesia.

Abnormal systolic blood pressure response during exercise recovery in patients with angina pectoris

Objectives. This study was conducted to clarify the mechanisms of the abnormal systolic blood pressure response after exercise in patients with angina pectoris.Background. An abnormal systolic blood pressure response in patients with angina pectoris has been observed not only during exercise but also during the recovery period after exercise. However, the mechanisms of this abnormal response during recovery have not been elucidated.Methods. Thirty-five patients with angina pectoris and 17 control subjects underwent bicycle ergometric studies after insertion of a Swan-Ganz catheter.Results. In control subjects, all hemodynamic variables decreased rapidly after exercise. In 7 of the 35 patients, systolic blood pressure increased after exercise. The patients with angina were classified into two groups. In group I (17 patients), changes in systolic blood pressure during recovery were smaller than those in control subjects. In group II (18 patients) recovery of systolic blood pressure was normal. Changes in stroke index from rest to peak exercise were smaller in group I than in group II. Stroke index in both patient groups increased paradoxically during recovery. The increase in systemic vascular resistance index during recovery and the ratio of plasma norepinephrine concen tration to cumulative work load were greater in group I than in group II.Conclusions. An abnormal systolic blood pressure response after physical exercise in patients with angina pectoris is indicative of severe myocardial ischemia during exercise and may be caused by an increase in stroke volume due to recovery from myocardial ischemia and increased systemic vascular resistance secondary to exaggerated sympathetic nervous activity.

Renovascular hypertension: Predicting surgical cure with exercise renography

Renal artery stenosis with resultant renovascular hypertension has attracted clinical attention because the disease is potentially curable and because numerous diagnostic and therapeutic modalities compete for clinical acceptance. An exercise-mediated disturbance of renal hippurate transport was recently described, and has been implicated as having a role in nephrogenic fixed hypertension. To predict the final course of renovascular hypertension before operation we carried out a prospective study with the goal of verifying the predictive value of exercise hippurate scintigraphy. The study was to test the hypothesis that patients with disturbance of renal hippurate transport (pathologic renogram) induced by exercise would have stabilized hypertension and would continue to be hypertensive after operation. Thirty-one patients with hypertension who had unilateral or bilateral renovascular stenosis documented on angiography were referred to rest and exercise hippurate scintigrams before operation. The results of the examinations at rest served as standard and were compared with the exercise scintigrams. In 19 of the 31 (61%) patients a disturbance of transrenal hippurate transport evolved during exercise, whereas 12 (39%) patients failed to respond to exercise with altered hippurate kinetics. Twenty-six patients went on to renovascular operations; five had percutaneous transluminal angioplasty. Revascularization results differed markedly when the blood pressure response of patients with positive results on exercise (abnormal) and patients with negative results on exercise (normal) were compared. Ten of 12 patients with hypertension who had normal exercise renograms were cured. In comparison, blood pressure values were little influenced by therapy in patients with an abnormal response, where 17 of 19 patients continued to have hypertensive disease after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin inhibition with A-64662: effect on blood pressure and hormonal response in man.

We studied the effects of intravenous injections of the renin inhibitor A-64662 on blood pressure, plasma renin activity (PRA), angiotensin II (Ang II) and aldosterone levels in patients with essential hypertension. While PRA was completely suppressed with doses as small as 0.001 microgram/kg, blood pressure was affected only in a few instances in doses of 0.4-1.0 mg/kg. In the six patients in whom Ang II and aldosterone results were available these hormones were concomitantly reduced with PRA, although the PRA inhibition lasted much longer (up to 24 h). There was little relationship between the blood pressure changes and plasma levels of renin activity, Ang II and aldosterone, suggesting that the plasma pool of these variables may not be the crucial factor determining blood pressure responses in patients with essential hypertension.

Cardiovascular responses to early exercise in inferior wall ST acute myocardial infarction

The heart rate and blood pressure responses to standardized exercise tests were studied in a group of patients with electrocardiographic evidence of inferior wall acute myocardial infarction (AMI). The tests were done on a bicycle ergometer at 8 to 10 days and 10 to 12 weeks after AMI. At 8 to 10 days after AMI, those with ST AMI (n = 12) had a significantly reduced heart rate response to exercise compared with patients with Q-wave AMI (n = 25). This difference was not evident at 10 to 12 weeks. The systolic blood pressure response in patients with ST AMI was lower than that of Q-wave AMI patients during the first exercise test, although the difference did not attain statistical significance but was significantly lower than the responses of both groups at the second test. The patients with ST AMI had smaller amounts of myocardial damage than those with Q-wave AMI as indicated by plasma creatine kinase values (p < 0.01). These differences in the heart rate responses appeared to result from the preferential activation of nonmyelinated afferent fibers in the subepicardial region of the inferior wall of the myocardium.

Pressor Response During Cystomanometry in Spinal Injury Patients Complicated with Detrusor-Sphincter Dyssynergia

Herein attention is focused on the documentation of high blood pressure response with detrusorsphincter dyssynergia in spinal cord injury patients and with its amelioration after extended sphincterotomy. During cystomanometric evaluation of the bladder the monitored blood pressure response in 53 spinal injury patients, 27 non-dyssynergic spinal injury patients and 18 non-spinal injury patients was compared. A high correlation was observed among the magnitudes of blood pressure increase, level of injury and the severity of detrusor-sphincter dyssynergia in spinal injury patients. During cystomanometry blood pressure increases of >20mm. Hg systolic and 10mm. Hg diastolic in normotensive paraplegics (below T5) and also in non-spinal injury patients were significant to suspect detrusor-sphincter dyssynergia. In normotensive tetraplegic patients blood pressure increases of >40mm. Hg systolic and 20mm. Hg diastolic were significant to suspect detrusor-sphincter dyssynergia. The mechanism of blood pressure increase is elucidated. The management of this high blood pressure response in patients with detrusor-sphincter dyssynergia by drug therapy and extended sphincterotomy is discussed. Based on our experience the use of carbon dioxide for cystomanometry seems preferable in patients with spinal lesions above T5 since expedient deflation of the bladder can prevent an inordinate blood pressure increase.

THE EFFECT OF INTRAVENOUS HISTAMINE ON THE URINARY EXCRETION OF EPINEPHRINE, NOREPINEPHRINE, AND 3-METHOXY-4-HYDROXYMANDELIC ACID IN ESSENTIAL HYPERTENSION.

Abstract : A comparison is made of the pharmacologic effect of parenteral histamine on the urinary excretion rate of epinephrine, norepinephrine and VMA, and of the blood pressure response in patients with essential hypertension and nonhypertensive control subjects. (Author)