Nocturnal blood pressure and nocturnal blood pressure fluctuations: the effect of short-term CPAP therapy and their association with the severity of obstructive sleep apnea.

STUDY OBJECTIVES: We determined the relationship of cardiovascular risk factors, cardiovascular diseases, nocturnal blood pressure (NBP), and NBP fluctuations (NBPFs) with the severity of obstructive sleep apnea (OSA). We also investigated the effect of short-term continuous positive airway pressure therapy on NBP parameters. METHODS: This retrospective study included 548 patients from our cardiac clinic with suspected OSA. Patients underwent polysomnography and continuous NBP measurement using the pulse transit time. According to their apnea-hypopnea index (AHI), patients were subclassified as controls (AHI < 5 events/h), mild (AHI 5 to < 15 events/h), moderate (AHI 15 to < 30 events/h), and severe OSA (AHI ≥ 30 events/h); 294 patients received continuous positive airway pressure therapy. RESULTS: Analysis of covariance showed that NBP and the frequency of NBPFs were the highest in severe followed by moderate and mild OSA (all P < .001). Multivariable regression analysis revealed a significant association of NBPFs with AHI, body mass index, systolic NBP, and lowest SpO2. The severity of OSA is also associated with the frequency of obesity, hypertension, diabetes mellitus, atrial fibrillation, heart failure (all P < .001), and coronary artery disease (P = .035). Short-term continuous positive airway pressure decreased the frequency of NBPFs in all OSA groups and the systolic NBP in severe and moderate but not in mild OSA. CONCLUSIONS: The severity of OSA is associated with an increase in NBP and NBPFs. Continuous positive airway pressure reduces NBP parameters already after the first night. In addition to BP, the diagnosis and therapy of NBPFs should be considered in patients with OSA. CLINICAL TRIAL REGISTRATION: Registry: German Clinical Trials Register; Name: Nocturnal blood pressure and nocturnal blood pressure fluctuations associated with the severity of obstructive sleep apnea; URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024087; Identifier: DRKS00024087. CITATION: Picard F, Panagiotidou P, Tammen A-B, et al. Nocturnal blood pressure and nocturnal blood pressure fluctuations: the effect of short-term CPAP therapy and their association with the severity of obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):361-371.

Effect of CPAP therapy on nocturnal blood pressure fluctuations, nocturnal blood pressure, and arterial stiffness in patients with coexisting cardiovascular diseases and obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) can induce dramatic nocturnal blood pressure fluctuations (NBPFs) and can be associated with nocturnal hypertension and arterial stiffness. We investigated the effect of short- and long-term continuous positive airway pressure (CPAP) therapy on NBPFs, nocturnal blood pressure (BP), and arterial stiffness in patients with coexisting cardiovascular diseases (CVD) and OSA (CVD/OSA). METHODS: Of 86 patients with CVD, 58 also had OSA, while 28 without OSA served as controls. Nighttime BP was measured continuously using pulse transit time (PTT) and arterial stiffness was measured with pulse wave velocity (PWV). A NBPF was defined as systolic BP elevation > 12 mmHg in a 30 s interval of sleep. All measurements were conducted at baseline, after the first night of CPAP, and after 6 months of CPAP therapy. RESULTS: In CVD/OSA patients, we observed significantly more frequent NBPFs (p < 0.001) compared with controls. CPAP therapy decreased the frequency of NBPFs (p < 0.001), the maximum systolic BP by 9 mmHg (p = 0.021), and PWV (p < 0.001) even after the first night. After long-term CPAP therapy, there was an additional decrease in average nocturnal systolic BP by 10 mmHg (p = 0.039). CONCLUSIONS: Our findings demonstrate that CPAP therapy reduces NBPFs, nocturnal BP, and arterial stiffness in CVD/OSA patients. This effect was demonstrable after the first night of CPAP and grew more robust after 6 months of CPAP therapy.

Individual shear rate therapy (ISRT)-further development of external counterpulsation for decreasing blood pressure in patients with symptomatic coronary artery disease (CAD).

Individual shear rate therapy (ISRT) evolved from external counterpulsation with individual treatment pressures based on Doppler ultrasound measurements. In this study, we assessed the effect of ISRT on blood pressure (BP) in patients with coronary artery disease (CAD). Eighty-four patients with symptomatic CAD were included in the study. Forty-one patients were enrolled for 6 weeks, comprising 30 sessions of ISRT; 43 age- and sex-matched patients represented the control group. The 24-h BP was determined by measuring the pulse transit time before and after 6 weeks of ISRT or the time-matched control. Participants were divided into three groups according to the 24-h BP before treatment: BP1 < 130/80 mmHg (normotensive); BP2 ≥ 130-140/80 mmHg (moderate hypertensive); BP3 > 140/80 mmHg (hypertensive). After 30 sessions of ISRT, the 24-h BP decreased significantly, whereas no changes were observed in the controls. The BP-lowering effect correlated with the 24-h BP before therapy (systolic: r = -0.78; p < 0.001; diastolic: r = -0.76; p < 0.001). In BP1, the systolic BP decreased by 4.3 ± 6.4 mmHg (p = 0.011), and the diastolic BP decreased by 4.8 ± 11.0 mmHg (p = 0.032); in BP2, the systolic BP decreased by 13.3 ± 7.5 mmHg (p < 0.001), and the diastolic BP decreased by 5.0 ± 7.5 mmHg (p = 0.002); and in BP3, the systolic BP decreased by 22.9 ± 11.4 mmHg (p < 0.001), and the diastolic BP decreased by 9.1 ± 9.5 mmHg (p = 0.003). Our findings demonstrate that ISRT reduces BP in patients with CAD. The higher the initial BP the greater the lowering effect.

Usefulness of Individual Shear Rate Therapy, New Treatment Option for Patients With Symptomatic Coronary Artery Disease.

The aim of this study was to elucidate if patients with coronary artery disease (CAD), who fail to respond to revascularization procedures, can improve from individual shear rate therapy (ISRT). The ISRT is an adaptation of the external counterpulsation with lower individual treatment pressures based on Doppler-ultrasound measurements during counterpulsation. In contrast to the external counterpulsation therapy, the ISRT is based on the detection of the individual intra-arterial shear rate. Here we report about the first clinical trial of 31 patients with CAD who were enrolled for 30 sessions of ISRT. To determine the therapeutic effect of ISRT we measured the exercise capacity, the arterial stiffness, the aortic wave reflection, and the 24-hour blood pressure before and after 30 treatment sessions. After 6 weeks of accomplished ISRT the walking distance during the 6-minute walking test extended by 78 m (p = 0.007). The total exercise duration in the exercise stress electrocardiogram increased by 84 seconds (p = 0.012) but not the stress intensity (p = 0.086). The pulse wave velocity decreased by 1.2 m/s (p = 0.004) and demonstrated a decrease in arterial stiffness. Pulse wave analysis results demonstrated a progressive decrease in central blood pressure by 12 mmHg (p = 0.008), in pulse pressure by 9 mmHg (p = 0.005), and in augmentation pressure by 5.3 mmHg (p = 0.004). The 24-hour blood pressure decreased systolic by 15 mmHg (p <0.001) and diastolic by 8 mmHg (p = 0.033). The patients also benefited subjectively followed by New York Heart Association and Canadian Cardiovascular Society classifications. In conclusion, the ISRT is an effective treatment for patients with CAD to improve cardiac fitness, arterial stiffness, and to reduce blood pressure.

Accumulation of VEGFR-2+/CD133+ cells and decreased number and impaired functionality of CD34+/VEGFR-2+ cells in patients with SLE.

OBJECTIVE: Inflammation and atherosclerosis are the major causes of cardiovascular disease (CVD) in SLE. Both traditional and disease-specific risk factors contribute to the formation of endothelial dysfunction. Endothelial progenitor cells (EPCs) have the ability to restore endothelial integrity. The aim of this study was to determine whether the number and function of EPCs are altered in SLE. METHODS: Nineteen patients with SLE and 19 controls were analysed. VEGF receptor-2 (VEGFR-2)(+)/CD133(+) and CD34(+)/VEGFR-2(+) cells were quantified by flow cytometry. EPC differentiation was measured by DiI-acLDL/Lectin I staining. Furthermore, apoptosis, proliferation capacity, migration capacity and clonogenic ability of EPCs were determined. RESULTS: VEGFR-2(+)/CD133(+) cells were enhanced in SLE [215 (37) vs 122 (11) cells/1 x 10(6) lymphocytes; P = 0.029], whereas the number [106 (13) vs 215 (27) cells/1 x 10(6) lymphocytes; P = 0.002] and the proliferation rate [96% (6%) vs 143% (19%); P = 0.008] of CD34(+)/VEGFR-2(+) cells were decreased compared with controls. Additionally, EPCs in SLE showed an increased apoptosis [7% (1.4%) vs 3% (0.4%); P = 0.004], an impaired differentiation [36 (5) vs 121 (20) cells/mm(2); P < 0.001] and a reduced migratory capacity [116% (4%) vs 139% (4%); P = 0.001]. CONCLUSIONS: Our results suggest that the mobilization of progenitor cells is unaffected in SLE, but the diminished number and the altered functionality of circulating CD34(+)/VEGFR-2(+) cells reduce the ability to repair vascular damage and thus may trigger the development of atherosclerosis in SLE.

Enhanced mobilization of CD34(+) progenitor cells expressing cell adhesion molecules in patients with STEMI.

BACKGROUND: Adult stem cells can contribute to myocardial regeneration after ischemic injury. The aim of the study was to determine (1) the amount of mobilized CD34(+)/CD117(+), CD34(+)/KDR(+) cells into peripheral blood (PB) in relation to inflammatory and haematopoietic cytokines, (2) the presence of circulating CD34(+) cells, expressing cell adhesion molecules (CAM), in patients with ST-segment elevation myocardial infarction (STEMI) in comparison to patients with coronary artery disease (CAD). MATERIALS AND METHODS: Twenty-three patients with STEMI (<12 h), 24 patients with CAD and 15 control subjects were enrolled in this study. The patients were matched in age, 2-CAD, ejection fraction (45%) and end-diastolic volume index (70 ml/m(2)). The number of stem cells and the expression of adhesion molecules were quantified by use of flow cytometry. Inflammatory cytokines [interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor] and chemotactic factors as stromal cell-derived factor-1 (SDF-1), hepatocyte growth factor (HGF) were determined by ELISA. RESULTS: The amount of circulating progenitor cells including CD34(+)/CD117(+) and CD34(+)/KDR(+) cells was significantly higher in patients with STEMI than in patients with CAD (CD34(+)/CD117(+) 433 +/- 128 vs. 100 +/- 17, P = 0.012; CD34(+)/KDR(+) 253 +/- 41 vs. 128 +/- 24, P = 0.02). The mobilization of CD34(+) progenitor cells expressing CXCR4-receptor, lymphocyte function-associated antigen-1 (LFA-1), very late antigen-4 (VLA-4) and ICAM-1 into PB was significantly higher in patients with STEMI compared to CAD (CD34(+)/CXCR4(+) 740 +/- 327 vs. 136 +/- 23, P = 0.006; CD34(+)/LFA-1 976 +/- 227 vs. 329 +/- 41, P = 0.025; CD34(+)/VLA4(+) 830 +/- 161 vs. 330 +/- 31, P = 0.007; CD34(+)/ICAM(+) 387 +/- 66 vs. 144 +/- 26, P < 0.001). Additionally, the cytokines G-CFS, IL-6 and HGF were upregulated and significantly increase in the STEMI group compared with controls and CAD (G-CSF 50.6 +/- 6.8 vs. 23 +/- 3 vs. 23.8 +/- 2, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001; IL-6 8.4 +/- 0.6 vs. 3.8 +/- 1.9 vs. 2.6 +/- 1, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001; HGF 4,502 +/- 461 vs. 686 +/- 195 vs. 1,746 +/- 461, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001), while the level of SDF-1 was increased in patients with CAD compared to controls and patients with STEMI (3,035 +/- 286 vs. 2,028 +/- 76 vs. 2,154 +/- 234, P (Co vs. STEMI) = n.s., P (Co vs. CAD) = n.s., P (STEMI vs. CAD) = 0.005). CONCLUSIONS: The study demonstrates in patients with STEMI an increased mobilization of progenitor cells like CD34(+)/CD117(+) and CD34(+)/KDR(+) compared to CAD. Furthermore, we could shown that in patients with STEMI the mobilization of CD34(+) progenitor cells with expressed CAM was increased. It is to speculate that an enhanced expression of adhesion molecules may increase the transmigration and implantation of progenitor cells into ischemic myocardium for myocardial repair.

[Effects of exercise training on mobilization of BM-CPCs and migratory capacity as well as LVEF after AMI]. / Die Effekte von körperlichem Training auf die Mobilisation und funktionelle Aktivität zirkulierender Progenitorzellen aus dem Knochenmark sowie die LVEF nach akutem Myokardinfarkt.

BACKGROUND AND PURPOSE: Bone marrow-derived circulating progenitor cells (BM-CPCs) are mobilized in adult peripheral blood (PB) during the acute myocardial infarction (AMI) period and contribute to the regeneration of infarcted myocardium. In this study, the influence of physical training on the mobilization and the migratory activity of the BM-CPCs as well as on the left ventricular function (LVEF) after AMI was examined. PATIENTS AND METHODS: 26 patients with AMI were analyzed in two groups. The first group comprised 17 patients with standardized exercise training for 3 weeks 14 +/- 4 days after AMI, the second group nine control subjects without exercise training. PB concentrations of CD34/45+ and CD133/45+ were measured by FACS. The migratory activity of BM-CPCs was analyzed by migration assay. B-type natriuretic peptide (BNP) in PB and the functional investigations spiroergometry (VO2 and PaO2) and stress echocardiography (LVEF) were determined in both groups. RESULTS: A significant increase in both concentrations, CD34/45+ and CD133/45+, as well as in migratory capacity of BM-CPCs was found after 3 weeks of exercise training, which was significantly decreased 3 months after completion of exercise training. No significant difference was observed in the control group without exercise training. In the functional investigations a significant increase in VO2 as well as PaO2 was shown spiroergometrically after exercise training. There was no difference in stress echocardiographic LVEF at rest in both groups. On the other hand, interestingly, the findings showed that the increase of LVEF at peak stress was significantly higher after exercise training as compared to the control group. Moreover, a significant decrease in BNP values was found after exercise training as well as 3 months after AMI. No difference was found in the control group. CONCLUSION: This study demonstrates that exercise training for 3 weeks after AMI leads to a significant mobilization as well as increase of functional activation of BM-CPCs in humans. Moreover, regular exercise training might contribute to the positive effects on the regenerative potency after AMI.

Detection of enteroviral RNA (poliovirus types 1 and 3) in endomyocardial biopsies from patients with ventricular tachycardia and survivors of sudden cardiac death.

The purpose of this study was to determine the prevalence of enteroviral infection in the myocardium of consecutive patients with serious ventricular arrhythmias by using a reverse transcription nested PCR followed by direct DNA sequencing. After exclusion of coronary heart disease, right ventricular endomyocardial biopsies were obtained from 32 consecutive patients with a history of ventricular tachycardia or sudden cardiac death. Control biopsies were obtained from 36 subjects with no history of viral myocarditis, dilated cardiomyopathy, ventricular tachycardia or recent infection. Enteroviral genome was found in endomyocardial biopsies from 4/32 patients (12.5%), 2 with a history of ventricular tachycardia and 2 with a history of ventricular fibrillation. Three of these 4 enteroviral RNA-positive patients had dilated cardiomyopathy and the other had normal cardiac geometry and ventricular function. In the latter and in 1 patient with enteroviral-positive dilated cardiomyopathy, an active inflammatory process in the myocardium was found by means of immunohistology. Enteroviral RNA in the myocardium of 3 patients had the highest homology to poliovirus type 1 (strain CHAT 10A-11) and in the other was similar to poliovirus type 3 (strain P3/119). All control samples were negative for enteroviral RNA. In summary, these findings raise the possibility that enteroviruses, such as poliovirus types 1 and 3, may be involved in the pathogenesis of ventricular tachycardia and sudden cardiac death.