Relationship between morning hypertension identified by home blood pressure monitoring and brain natriuretic peptide and estimated glomerular filtration rate: the Japan Morning Surge 1 (JMS-1) Study

We evaluated whether morning minus evening systolic blood pressure (SBP) difference (MEdif) in home blood pressure measurements can be a marker for hypertensive target organ damage. The authors analyzed 611 hypertensive patients who had high morning SBP levels (>/=135 mm Hg). The patients with morning hypertension (MEdif >/=15 mm Hg, average of morning and evening SBP [MEave] >/=135 mm Hg) were older (P<.001) and had a longer duration of hypertension and antihypertensive medication use, a higher prevalence of left ventricular hypertrophy (LVH) on electrocardiography, a lower glomerular filtration rate by the Cockcroft-Gault equation (P=.002), and a higher brain natriuretic peptide (BNP) level (P<.001) than those with well-controlled blood pressure (MEdif <15 mm Hg, MEave <135 mm Hg). The patients with morning hypertension had a higher BNP level than those with well-controlled blood pressure after adjustment for the confounding factors (28.7 pg/mL vs 20.0 pg/mL; P=.033). In conclusion, morning hypertension is more likely seen among patients with older age and longer duration of hypertension and antihypertensive medication use, and it may be associated with a higher prevalence of LVH and a higher BNP level.     

An alpha-adrenergic blocker titrated by self-measured blood pressure recordings lowered blood pressure and microalbuminuria in patients with morning hypertension: the Japan Morning Surge-1 Study

BACKGROUND: The impact on microalbuminuria of strict treatment aimed at lowering of self-measured morning blood pressure using an adrenergic blockade is unclear. METHODS: We conducted an open-label multicenter trial, the Japan Morning Surge-1 Study, that enrolled 611 hypertensive patients, whose self-measured morning systolic blood pressure levels were more than 135 mmHg while taking antihypertensive drugs. These were randomly allocated to an experimental group, whose members received bedtime administration of 1-4 mg doxazosin (doxazosin group) or a control group whose members continued without any add-on medication (control group). The urinary albumin/creatinine ratio was investigated at the baseline and 6 months after the randomization. RESULTS: Both the morning and evening blood pressures and urinary albumin/creatinine ratio (-3.4 vs. 0.0 mg/gCr for urinary albumin/creatinine ratio; P < 0.001) were more markedly reduced in the doxazosin group than in the control group. This difference in the urinary albumin/creatinine ratio between the two groups was more marked in the patients with microalbuminuria (n = 238, -27.9 vs. -8.1 mg/gCr, P < 0.001). The reduction of urinary albumin/creatinine ratio was significantly associated with the use of doxazosin, and the change in all self-measured blood pressures (morning, evening, the average morning-evening), and these associations were independent of each other (P < 0.001). CONCLUSION: Adding a bedtime dose of an alpha-adrenergic blocker titrated by self-measured morning blood pressure in treated hypertensive patients with uncontrolled morning hypertension significantly reduced blood pressure and urinary albumin excretion rate, particularly in those with microalbuminuria.     

The defibrillator in acute myocardial infarction trial (DINAMIT): study protocol

BACKGROUND: The implantable cardioverter/defibrillator (ICD) has been shown to be superior to antiarrhythmic drug therapy for the secondary prevention of sudden cardiac death. Its role in the primary prevention of sudden death after myocardial infarction is unknown.Methods and Results The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) is a randomized, open-label, parallel-group comparison of ICD therapy versus no ICD therapy in selected survivors of acute myocardial infarction. It will test the hypothesis that reduction of sudden arrhythmogenic death by means of the ICD will result in reduction of overall mortality rates in patients at high risk after acute myocardial infarction. Accordingly, this international multicenter study aims to enroll patients shortly after their infarction (day 6 to day 40) who have reduced left ventricular function (left ventricular ejection fraction 相似文献   

The TORCH (towards a revolution in COPD health) survival study protocol.

Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 microg), fluticasone propionate (500 microg), salmeterol (50 microg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.     

Immediate Risk-Stratification Improves Survival (IRIS): study protocol

BACKGROUND: To date, the implantable cardioverter-defibrillator (ICD) hasbeen shown to be effective for primary prevention of suddencardiac death only in selected groups of patients in the chronicphase after myocardial infarction. METHODS AND RESULTS: The Immediate Risk-Stratification Improves Survival (IRIS) Studycompares ICD therapy with no ICD therapy in selected high riskpatients early after myocardial infarction. Special emphasisis placed on optimal acute and long term medical therapy inall patients including metoprolol CR/ZOK. The hypothesis istested that use of the ICD reduces overall mortality. For thatpurpose, consecutive acute ST elevation or non-ST elevationmyocardial infarction patients are collected in a registry.From this denominator, patients are screened, and enroled earlyafter myocardial infarction (day 5 to day 31) if they exhibitboth a reduced left ventricular ejection fraction 40% and aheart rate 100 bpm on the first available electrocardiogram(criterion I), or non-sustained ventricular tachycardia at arate 150 bpm during Holter (criterion II). CONCLUSIONS: IRIS is a large scale prospective, randomized trial to evaluatethe benefit of ICD therapy for reduction of total mortalityin patients considered at high risk of sudden death early afteracute myocardial infarction.     

The resynchronization therapy in narrow QRS study (RethinQ study): Methods and protocol design

Background Numerous trials have demonstrated the effectiveness of cardiac resynchronization therapy (CRT) as an adjunct to medical therapy for the relief of heart failure (HF) symptoms in patients with a wide QRS duration (QRSd). Current guidelines recommend CRT in patients with an EF <35%, medically refractory NYHA Class III–IV HF and QRSd ≥120 ms. Previous studies have demonstrated QRSd as a marker of electrical dyssynchrony fails to predict response to CRT. In addition, studies have demonstrated significant differences in QRSd post CRT between responders and non-responders. Moreover, smaller non-controlled studies demonstrated that HF patients with a narrow QRSd may benefit from CRT. A growing body of evidence suggests that echocardiographic criteria may be a better method to evaluate mechanical dyssynchrony (MD) which may predict those that will benefit from CRT, particularly those with a narrow QRSd. The Resynchronization Therapy In Narrow QRS (RethinQ) study will evaluate mechanical dyssynchrony using echocardiography (both M mode and TDI) as an eligibility requirement for CRT. Methods The RethinQ study is a prospective, multi-center, randomized, double blind controlled clinical study. The objective of the RethinQ study is to evaluate the effectiveness of CRT in patients with approved ICD indication, advanced HF (NYHA Classification III), narrow QRSd (<130 ms) and evidence of MD measured by echocardiography. Conclusion We hypothesize that patients with narrow QRS <130 ms, advanced HF, and MD as measured by echocardiography will benefit from CRT. An erratum to this article can be found at     

Effect of doxazosin on the left ventricular structure and function in morning hypertensive patients: the Japan Morning Surge 1 study

OBJECTIVES: Doxazosin is reported to increase the incidence of congestive heart failure. The benefits of doxazosin, for controlling morning blood pressure as well as its effect on the left ventricular structure and function, are herein examined. METHODS: In this study, 223 morning hypertensive patients were randomized into either the doxazosin group, with a once-daily bedtime dose of doxazosin, or the control group, who continued their current medication. Atenolol was added to the doxazosin group when needed. The effect of doxazosin was evaluated by measurement of echocardiographic parameters and B-type natriuretic peptide. RESULTS: The left ventricular wall thickness decreased, but the left ventricular diastolic diameter in the doxazosin group increased from the baseline. The changes in the left ventricular mass index were similar between the groups, whereas the relative wall thickness in the doxazosin group decreased more than that in the control group. The left ventricular diastolic function could deteriorate in the doxazosin group. In the doxazosin group, an increase in the left ventricular diameter was only seen in the patient who did not take diuretics throughout the study. The office and home blood pressure in the doxazosin group decreased more than that in the control group, whereas the B-type natriuretic peptide increased in the doxazosin group. Three cases of congestive heart failure were observed in the doxazosin group, but none in the control group. CONCLUSION: Although a bedtime dose of doxazosin can significantly lower the blood pressure, it can also increase left ventricular diameter, thus increasing the risk of congestive heart failure. However, the prior use of diuretics can prevent the unfavorable effects of doxazosin on the left ventricular structure.     

The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report.

OBJECTIVES: The Women's Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute-sponsored, four-center study designed to: 1) optimize symptom evaluation and diagnostic testing for ischemic heart disease; 2) explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenoses, and 3) evaluate the influence of reproductive hormones on symptoms and diagnostic test response. BACKGROUND: Accurate diagnosis of ischemic heart disease in women is a major challenge to physicians, and the role reproductive hormones play in this diagnostic uncertainty is unexplored. Moreover, the significance and pathophysiology of ischemia in the absence of significant epicardial coronary stenoses is unknown. METHODS: The WISE common core data include demographic and clinical data, symptom and psychosocial variables, coronary angiographic and ventriculographic data, brachial artery reactivity testing, resting/ambulatory electrocardiographic monitoring and a variety of blood determinations. Site-specific complementary methods include physiologic and functional cardiovascular assessments of myocardial perfusion and metabolism, ventriculography, endothelial vascular function and coronary angiography. Women are followed for at least 1 year to assess clinical events and symptom status. RESULTS: In Phase I (1996-1997), a pilot phase, 256 women were studied. These data indicate that the WISE protocol is safe and feasible for identifying symptomatic women with and without significant epicardial coronary artery stenoses. CONCLUSIONS: The WISE study will define contemporary diagnostic testing to evaluate women with suspected ischemic heart disease. Phase II (1997-1999) is ongoing and will study an additional 680 women, for a total WISE enrollment of 936 women. Phase III (2000) will include patient follow-up, data analysis and a National Institutes of Health WISE workshop.     

Case-control study on analgesics and nephropathy (SAN): protocol

Background

The association between intake of non-phenacetin-containing analgesics and the occurrence of chronic renal failure is still controversially discussed. A new epidemiologic study was planned and conducted in Germany and Austria.

Methods/design

The objective of the international, multicenter case-control study was to evaluate the association between end-stage renal disease (ESRD) and use of non-phenacetin-containing analgesics with particular emphasis on combined formulations. A targeted sample of 1000 new (incident) dialysis patients, aged less than 50 years, was planned to recruit between January 1, 2001 and December 31, 2004. The age limit was chosen to avoid contamination of the study population with phenacetin-containing analgesics to the extent possible. Four control subjects per ESRD case, matched by age, sex, and region were selected from the population living in the region the case came from. Lifetime exposure to analgesics and potential renal risk factors were recorded in a single face-to-face interview. A set of aids was introduced to reinforce the memory of study participants. A standardized, pre-tested interview questionnaire (participants), a medical documentation sheet (physicians in dialysis centres), a logbook for all activities (dialysis centres) were used to collect the necessary data. Quality management consisted of the standardized procedures, (re-) training and supervision of interviewers, regular checks of all incoming data for completeness and plausibility. The study is scientifically independent and governed by a international Scientific Advisory Committee that bridged the gap between the sponsoring companies and the investigators. Also other advisory groups assisted the managing committee of the study. All relevant German and Austrian nephrological associations supported the study, and the study design was carefully reviewed and approved by the Kidney Foundation of Germany.

Discussion

The study is expected to answer the main research question by end 2005. There is however a high potential for various biases that we tried to address with adequate measure. One limitation however cannot be overcome: The methodologically needed age-limitation of the study will make it not easy to generalize the results to age groups over 50 years. It might be suggested to repeat the study for persons over 50 years in 10 years when contamination with phenacetin use early in life is likely to be outgrown.     

Monitoring of the central pulse pressure is useful for detecting cardiac overload during antiadrenergic treatment: the Japan Morning Surge 1 study

OBJECTIVE: Lowering of the central pulse pressure (PP) has been shown to contribute to an improvement of the cardiac damage beyond that of lowering the brachial PP. We assessed the hypothesis that the change in the central PP is more useful than that in the brachial PP in the assessment of the change in cardiac load. METHODS: We studied 434 treated hypertensive patients whose home systolic blood pressure was 135 mmHg or higher. They were followed for 6 months after allocation to either a control group or an added treatment group (doxazosin 1-4 mg and atenolol when needed). We measured the brachial and central (carotid) blood pressure simultaneously using a validated device, and the B-type natriuretic peptide at baseline and at the sixth month of treatment. RESULTS: In the added treatment group, the brachial systolic blood pressure was successfully reduced, but the central PP increased significantly, whereas the other blood pressure parameters did not change from the baseline. In the added treatment group, the change in the B-type natriuretic peptide was significantly correlated with the change in the brachial PP (r = 0.18), central systolic blood pressure (r = 0.18), central PP (r = 0.26), and PP amplification (r = -0.22) even after adjusting for the confounding factors. The correlation with the central PP was stronger than with the brachial PP (P = 0.018) or central systolic blood pressure (P = 0.002), and these relationships were essentially the same even after adjustment for the use of atenolol or the change in heart rate. CONCLUSION: This study showed that the central PP measurement may be more important to assess cardiac load than the brachial PP during antiadrenergic treatment.     

The longitudinal urban cohort ageing study (LUCAS): study protocol and participation in the first decade

Background

Care for older adults is facing a number of challenges: health problems are not consistently identified at a timely stage, older adults report a lack of autonomy in their care process, and care systems are often confronted with the need for better coordination between health care professionals. We aim to address these challenges by introducing the geriatric care model, based on the chronic care model, and to evaluate its effects on the quality of life of community-dwelling frail older adults.

Methods/design

In a 2-year stepped-wedge cluster randomised clinical trial with 6-monthly measurements, the chronic care model will be compared with usual care. The trial will be carried out among 35 primary care practices in two regions in the Netherlands. Per region, practices will be randomly allocated to four allocation arms designating the starting point of the intervention. Participants: 1200 community-dwelling older adults aged 65 or over and their primary informal caregivers. Primary care physicians will identify frail individuals based on a composite definition of frailty and a polypharmacy criterion. Final inclusion criterion: scoring 3 or more on a disability case-finding tool. Intervention: Every 6 months patients will receive a geriatric in-home assessment by a practice nurse, followed by a tailored care plan. Expert teams will manage and train practice nurses. Patients with complex care needs will be reviewed in interdisciplinary consultations. Evaluation: We will perform an effect evaluation, an economic evaluation, and a process evaluation. Primary outcome is quality of life as measured with the Short Form-12 questionnaire. Effect analyses will be based on the ??intention-to-treat?? principle, using multilevel regression analysis. Cost measurements will be administered continually during the study period. A cost-effectiveness analysis and cost-utility analysis will be conducted comparing mean total costs to functional status, care needs and QALYs. We will investigate the level of implementation, barriers and facilitators to successful implementation and the extent to which the intervention manages to achieve the transition necessary to overcome challenges in elderly care.

Discussion

This is one of the first studies assessing the effectiveness, cost-effectiveness and implementation process of the chronic care model for frail community-dwelling older adults.

Trial registration

The Netherlands National Trial Register NTR2160.     

Association of lower nighttime diastolic blood pressure and hypoxia with silent myocardial injury: The Japan Morning Surge‐Home Blood Pressure study

Whether marked nocturnal blood pressure (BP) reduction is associated with cardiovascular disease (CVD) is still controversial. In addition, no report has yet discussed the relationship between lower nocturnal BP and CVD, involving modification by nighttime hypoxia. We evaluated 840 patients who had one or more cardiovascular risk factors by measuring their high‐sensitivity cardiac troponin T (Hs‐cTnT), N‐terminal pro‐B‐type natriuretic peptide (NT‐pro BNP), and nighttime saturation levels and performing ambulatory BP monitoring. The lowest tertile in nighttime diastolic BP (DBP) (≤66 mmHg) had increased likelihood of the presence of ≥0.014 ng/ml of Hs‐cTnT compared with the second tertile (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.01–3.63), and the lowest tertile of minimum blood oxygen saturation (≤81%) had increased likelihood of the presence of ≥0.014 ng/ml of Hs‐cTnT compared with the third tertile (OR 2.15, 95% CI 1.13–4.10). Additionally, the patients with both lowest tertile of nighttime DBP and minimum SpO2 showed increased likelihood of the presence of ≥0.014 ng/ml of Hs‐cTnT compared with those without this combination (OR 2.93, 95% CI 1.40–6.16). On the other hand, these associations were not found in the presence of ≥125 pg/ml of NT‐pro BNP. In the clinical population, each of lower nocturnal DBP and nighttime hypoxia was associated with asymptomatic myocardial injury, which was represented as higher Hs‐cTnT, and coexisting lower nocturnal DBP and nighttime hypoxia had an additive effect on the risk of myocardial injury.