In adults with SMA, risdiplam therapy may improve respiratory function. In these patients, sniff nasal inspiratory pressure is the most effective test to demonstrate effects of pharmacological therapy. https://bit.ly/3Wk2MCU.

OBJECTIVES:Investigations on effects of risdiplam therapy in adult patients with Spinal Muscular Atrophy (SMA) have been limited to diurnal respiratory and motor function. We explored whether risdiplam can influence nocturnal respiratory events and autonomic function. METHODS:Sixteen consecutive subjects ≥16 years old with SMA type 2 or 3 were studied before and 12 months after risdiplam therapy. They underwent nocturnal cardiorespiratory polygraphy for analysis of respiratory function and heart rate variability (HRV). In addition, their motor function was evaluated using the Revised Upper Limb Module (RULM) and the Hammersmith Functional Motor Scale Expanded (HFMSE) scales. RESULTS:After therapy, apnoea/hypopnoea Index (AHI) and oxygen desaturation index decreased (p = 0.02), while time with oxygen saturation <90% and lowest oxygen saturation did not change. HRV analysis showed a decrease in the SD2/SD1 ratio (p = 0.03), suggesting a decrease in sympathovagal balance. RULM and HFMSE scores showed a borderline improvement. The SD2/SD1 change was correlated with the change in AHI but not with the change in respiratory function or motor scale scores. CONCLUSIONS:In adult patients with SMA, risdiplam therapy may be associated with improvements in nocturnal respiratory function and autonomic activity. The reduction in respiratory events during sleep may contribute to improved autonomic balance.

Abstract Introduction In late-onset Pompe disease (LOPD), muscle weakness causes restrictive lung impairment. In murine models, glycogen deposition in lung parenchyma suggests additional causes for restriction that remain poorly understood. We investigated whether oscillometry detects respiratory abnormalities not identified by spirometry and evaluated changes after air-stacking manoeuvres. Methods We prospectively evaluated 16 adults with LOPD from three Italian centres. Alongside spirometry, oscillometry (at 5, 11, and 19 Hz) was performed to assess resistance (R) and reactance (X) across the breathing cycle and by respiratory phase. Measurements were repeated 5 min after an air-stacking manoeuvre. Results Participants (7 men, 9 women; 51.6 ± 12.5 years) had moderate-to-severe restriction (FVC 53.3 ± 19.6% predicted) with preserved FEV1/FVC. Two oscillometric patterns emerged. The first one (seven patients) was characterised by an abnormal increase in expiratory resistance within breaths ([R5exp − R5insp] > 0.70 cmH 2 O·s/L), associated or not with abnormal whole-breath R and intrabreath X changes. The second pattern (nine patients) consisted of normal R and X changes in the breathing cycle. Air-stacking increased FVC (53.3 ± 19.6 to 71.3 ± 19.2% predicted, p < 0.001) without normalising reactance. Conclusion In LOPD, oscillometry detects distinct mechanical patterns not identified by spirometry. Air-stacking increases lung volumes without improving respiratory mechanics.

This study aimed to examine feasibility of inspiratory muscle strength tests, such as maximal inspiratory pressure (MIP) and sniff nasal inspiratory pressure (SNIP) in adult patients affected by spinal muscular atrophy (SMA), as well as their ability, along with forced vital capacity (FVC), to predict noninvasive ventilation (NIV) needs. Additionally, we evaluated feasibility and effectiveness of respiratory oscillometric measurements in the same patients. Twenty patients were retrospectively evaluated. NIV requirement was considered as peak nocturnal transcutaneous PCO2 > 49 mmHg, according to the cut-off used by Ward et al. MIP and SNIP were feasible in all patients. SNIP had significantly higher values (p < 0.001) and poorly agreed with MIP. ROC analysis revealed MIP as a weak predictor for NIV initiation (AUC = 0.57), while FVC (AUC 0.78, best cut-off 20% of predicted) and SNIP (AUC 0.84, best cut-off 61 cmH2O) were more effective. Oscillometry was performed in 11 patients. Reactance was abnormal in six of them and was significantly correlated with FVC (ρ = 0.70, p = 0.01) and SNIP (ρ = 0.72, p = 0.007), but not with MIP. In adult SMA patients, both MIP and SNIP are feasible, but SNIP is a better predictor of NIV needs, similar to FVC. Optimal predictive thresholds differed from those previously observed in neuromuscular disease. Oscillometric measurements may help to estimate FVC and SNIP in poorly collaborating patients.

SummarySleep‐disordered breathing is common among children with spinal muscular atrophy, but has been hardly studied among adult subjects. Little is known about sleep quality in spinal muscular atrophy. The aims of this study were to evaluate occurrence and characteristics of sleep‐disordered breathing and subjective sleep quality among adolescent and adult patients with spinal muscular atrophy type 2 or 3. Twenty patients aged 33.9 ± 15.2 years were studied. They underwent nocturnal cardiorespiratory monitoring, lung and muscular function evaluation, and were administered the Pittsburgh Sleep Quality Index questionnaire. Nineteen patients showed sleep‐disordered breathing, with obstructive events in seven subjects and non‐obstructive events in the remaining 12. In the latter group, 10 patients showed pseudo‐obstructive hypopneas. Patients with non‐obstructive sleep‐disordered breathing were younger (p = 0.042), had a lower body mass index (p = 0.0001), were more often affected by spinal muscular atrophy type 2 (p = 0.001), and showed worse impairment of respiratory function than patients with obstructive sleep‐disordered breathing. Ten patients were classified as poor sleepers and 10 patients good sleepers. In the whole sample, sniff nasal inspiratory pressure proved to be the only independent predictor of sleep quality (p = 0.009). In conclusion, sleep‐disordered breathing is common even among adult patients with spinal muscular atrophy type 2 and 3, and may show either obstructive or different types on non‐obstructive features. A worse respiratory muscle function is associated to non‐obstructive sleep‐disordered breathing and poorer sleep quality. Sleep quality should receive greater attention especially in patients with spinal muscular atrophy type 2, who have a poorer respiratory muscle function, as it could affect their quality of life.

•In spinal muscular atrophy, pseudo-obstructive events may occur during sleep.•Adjunctive criteria have been proposed to correctly classify them.•Event misclassification should be avoided to apply an appropriate therapy.

BACKGROUND:In Duchenne muscular dystrophy (DMD), dysphagia is a common but often overlooked symptom, which may affect quality of life (QoL). Its possible causes are progressive deterioration of muscle groups involved in swallowing function (oropharyngeal, inspiratory muscles) or impairment of autonomic function. OBJECTIVES:In adult patients with DMD, we aimed to identify predictors of swallowing-related QoL and to compare swallowing-related QoL at different ages. METHODS:Forty-eight patients aged 30.0±6.6 years were enrolled. Questionnaires were administered: the Swallowing Quality of Life questionnaire (SWAL-QOL) for swallowing-related QoL assessment, and the Compass 31 for autonomic symptoms assessment. The Brooke Upper Extremity Scale was used for upper limbs muscular function assessment. Respiratory and muscle function tests were performed, including spirometry, arterial blood gases, polysomnography, maximal inspiratory pressure (MIP), maximal expiratory pressure and sniff nasal inspiratory pressure. RESULTS:An abnormal composite SWAL-QOL score (≤86) was found in 33 patients. Autonomic symptoms were mild, while a severe impairment was shown by the Brooke Upper Extremity Scale. Spirometry and muscle strength tests demonstrated severe alterations, while diurnal and nocturnal blood gases were normal, due to effective use of noninvasive ventilation. Independent predictors of the composite SWAL-QOL score were age, MIP and Compass 31. A MIP < 22 had an accuracy of 92% in predicting altered swallowing-related QoL. The composite SWAL-QOL score was worse in subjects > 30 years old than in younger patients (64.5±19.2 vs 76.6±16.3, p < 0.02), due to worse scores in items pertinent to mental and social functioning; scores in domains pertinent to the physical function were similar in both groups. CONCLUSIONS:In adult DMD, swallowing-related QoL, which is altered in most patients, can be predicted by age, inspiratory muscles strength and autonomic dysfunction symptoms. While swallowing function is already altered in young patients, swallowing-related QoL can progressively worsen with advancing age due to psychological and social factors.

Objective: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time.Methods: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice.Results: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). Conclusion: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Cardiovascular events commonly cause death in amyotrophic lateral sclerosis (ALS) even in patients treated by noninvasive ventilation (NIV). Objectives: to evaluate autonomic function with the assessment of heart rate variability (HRV) in ALS patients treated by assist pressure control ventilation (APCV) and assist control ventilation (ACV) during sleep. Methods: Consecutive ALS patients underwent one polysomnography during APCV and one during ACV. HRV was analyzed both in the total sleep period (from first stage N1 to last awakening) and in a 5-minute period of stable stage N2. Time domain, frequency domain and nonlinear indexes of HRV were measured. Results: Nineteen patients (age 62.0 +/- 8.7, 9F/10 M) were studied. The analysis did not reveal differences in blood gasses between NIV modalities, but a longer expiratory time (3.01 +/- 0.6 vs 2.8 +/- 0.6 s, respectively APCV vs ACV, p = 0.001) and a lower arousal index (17.5 +/- 9.1 vs 23.1 +/- 13.9, p = 0.02) during APCV. HRV was indicative of higher vagal activity during APCV, especially in the 5-minute periods. In the total sleep periods, the HRV time domain indexes reflecting parasympathetic activity were positively correlated with the expiratory time and negatively with the inspiratory/expiratory time ratio. Low frequencies were positively, and high frequencies negatively, correlated with inspiratory time. HRV and sleep structure parameters were not correlated, except very low frequencies that were correlated to the arousal index. Conclusions: Respiratory influences on autonomic control can be preserved in ALS. The slower breathing pattern during APCV may help to maintain a higher vagal activity. Through this mechanism, in the long-term APCV could more beneficial to ALS patients than ACV. (C) 2022 Elsevier Inc. All rights reserved.

Background: respiratory failure due to muscular weakness is the main cause of death in amyotrophic lateral sclerosis (ALS). It has been suggested that, in ALS, serum levels of some biochemical indicators of iron homeostasis and energy metabolism, such as ferritin and uric acid, are altered and are associated with overall survival. Indeed, excessive iron causes oxidative stress and damage of cellular membranes, while uric acid is a natural antioxidant. We hypothesized that these substances could be related to indices of respiratory and muscle function. Methods: in 15 ALS patients, respiratory and muscle function were evaluated by sitting forced vital capacity (FVC), sniff nasal inspiratory pressure (SNIP), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and peak cough flow (PCF). In addition, serum ferritin and uric acid were determined. Results: we obtained the following results: FVC 1.72±1.0 L (54.7±25.1 % of predicted), SNIP 32.8±27.7 cmH2O, MIP 33.2±13.3 cmH2O, MEP 33.2±23.7 cmH2O, PCF 262.8±114.1 L/min, ferritin 279.9±243 ng/ml, and uric acid 5.1±2.3 mg/dl. SNIP and PCF were positively correlated to uric acid (ρ. 76, p=0.0009, and ρ. 53, p=0.04, respectively) and negatively to ferritin (ρ= -.64, p=0.009, and ρ= -.65, p=0.01). FVC (% of predicted) was only correlated to uric acid (ρ=. 62, p=0.005). Conclusions: in ALS, biomarkers of oxidative stress appear to be related to the strength of respiratory muscles, which supports their possible role as prognostic markers. SNIP better than FVC may reflect the association between respiratory and metabolic impairment in patients with this disease

BACKGROUND: Comparison of the effects of pressure controlled and volume controlled noninvasive ventilations (NIV) has usually been limited to the degree of improvement in blood gases. We compared sleep quality, abnormal respiratory events, and patient-ventilator asynchronies during administration of pressure controlled continuous mandatory ventilation (PC-CMV) and volume controlled continuous mandatory ventilation (VC-CMV) in subjects with amyotrophic lateral sclerosis naive to NIV after titration aimed at maximally improving nocturnal arterial blood gases. METHODS: A crossover evaluation of PC-CMV and VC-CMV was performed in 27 subjects with amyotrophic lateral sclerosis. After baseline polysomnography, ventilators were set in random order so as to warrant similar and satisfactory oxygen saturation and transcutaneous PCO2 in both NIV modalities during day and night. Soon after titration, polysomnography was repeated during administration of each type of NIV. RESULTS: With respect to the baseline night, non-rapid eye movement 3, and rapid eye movement sleep stages increased, and the arousal index decreased during PC-CMV (P = .005, P = .02, and P = .01, PC-CMV vs VC-CMV, respectively) but not during VC-CMV. The arousal index during NIV was correlated to the peak pressure delivered by the ventilators (ρ = 0.47, P < .001). Few abnormal respiratory events were observed in both NIV modes. Patient-ventilator asynchronies were more frequent during VC-CMV (median [IQR] 20.8 [0.0 – 22.0] vs 31.8 [30.1 – 34.0] no./h, PC-CMV vs VC-CMV; P = .002). Twenty-one subjects declared that they preferred PC-CMV therapy. CONCLUSIONS: In the short term, PC-CMV may be a preferred NIV modality to VC-CMV for patients with amyotrophic lateral sclerosis, even when both NIV modes are similarly effective in the correction of hypoventilation. Evaluation of the effectiveness of NIV should not be limited to the assessment of blood gas correction.

Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3–13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1–15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea–hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0–3 months, then it was 13–19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS (n = 2,190) was weakly correlated with CPAP use (R2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment.

The bidirectional relationship between sleep disordered breathing and chronic kidney disease (CKD) has recently gained a lot of interest. Several lines of evidence suggest the high prevalence of coexistent obstructive sleep apnea (OSA) in patients with CKD and end-stage renal disease (ESRD). In addition, OSA seems to result in loss of kidney function in some patients, especially in those with cardio-metabolic comorbidities. Treatment of CKD/ESRD and OSA can alter the natural history of each other; still better phenotyping with selection of appropriate treatment approaches is urgently needed. The aim of this narrative review is to provide an update of recent studies on epidemiological associations, pathophysiological interactions, and management of patients with OSA and CKD or ESRD.

Study Objectives Motor-vehicle crashes are frequent in untreated OSA patients but there is still uncertainty on prevalence as well as physiological or clinical determinants of sleepiness at the wheel (SW) in OSA patients. We assessed determinants of SW or sleepiness related near-miss car accident (NMA) in a group of non-professional drivers with OSA. Methods A 237 consecutive, treatment-naïve PSG-diagnosed OSA patients (161 males, 53.1 ± 12.6 years) were enrolled. Self-reported SW was assessed by positive answer to the question, “Have you had episodes of falling asleep while driving or episodes of drowsiness at wheel that could interfere with your driving skill in the last year?” Occurrence of NMA in the last 3 years was also individually recorded. Habitual self-reported average sleep time was collected. Results SW was found in 41.3% of patients but one-quarter of patients with SW did not report excessive daytime sleepiness. Predictors of SW were the following subjective factors: Epworth sleepiness scale score (ESS-OR 1.26; IC 1.1–1.4; p < 0.0001), depressive symptoms (BDI-OR 1.2; IC 1.06–1.18; p < 0.0001) and level of risk exposure (annual mileage-OR 1.9; IC 1.15–3.1; p = 0.007). NMAs were reported by 9.7% of patients, but more frequently by SW + than SW – (22.4% vs. 0.7%; χ 2 31, p < 0.0001). The occurrence of NMAs was significantly associated to ESS, BDI, habitual sleep duration and ODI ( R 2 = 0.41). Conclusion SW is not predicted by severity of OSA. Evaluation of risk exposure, assessment of depressive symptoms, and reported NMA should be included in the clinical evaluation, particularly in patients with reduced habitual sleep time and severe nocturnal hypoxia.

Objective In amyotrophic lateral sclerosis (ALS), early recognition of nocturnal hypoventilation (NH) is essential to start noninvasive ventilation (NIV), but nocturnal transcutaneous PCO2(PtcCO(2)) is difficult to monitor. Usefulness of respiratory and muscular function test in the prediction of NH has been explored without distinguishing among ALS phenotypes. We evaluated cross-sectional relationships between functional tests and nocturnal PCO2, and the best predictors of NH, separately in patients with spinal and bulbar onset of ALS.Methods: ALS patients candidate to NIV were recruited. Diurnal respiratory and muscular function tests and nocturnal polysomnography with PtcCO(2)monitoring were performed. NH was defined as peak PtcCO(2)>49 mm Hg.Results: Thirty-six patients with spinal and 11 with bulbar onset ALS were included. Nocturnal oxygen saturation and PtcCO(2), and proportion of subjects with NH were similar in each group (spinal: 50%; bulbar: 45.5%). Significant differences between groups were found in forced vital capacity (p = 0.03), maximal inspiratory pressure (p = 0.01) and sniff nasal inspiratory pressure (SNIP) (p = 0.007), but not in diurnal arterial blood gases. In the spinal group, SNIP and Base Excess (BE) independently predicted nocturnal PtcCO(2)(R(2)0.59,p < 0.0001). In the bulbar group only SNIP was correlated to PtcCO(2), but it varied little in relationship to PtcCO(2)changes.Conclusions: Respiratory and muscle function parameters are differently related to NH in ALS patients with spinal and bulbar presentation. SNIP and BE may be helpful to reveal NH in spinal patients, while in bulbar patients no respiratory or muscle function tests may reliably predict NH.

Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA.

Background: Respiratory outcomes in patients with late onset Pompe disease (LOPD) under enzyme replacement therapy (ERT) are usually evaluated by the measurement of upright forced vital capacity (FVC-U). However, a more comprehensive evaluation should also take into account the difference between upright and supine forced vital capacity, called postural drop (PD), which specifically reflects the performance of the diaphragm. So far, in these patients, studies on long-term changes of PD are not available, and the relationship between respiratory function and quality of life has not been investigated. Methods: We evaluated the trend of FVC-U and PD in six patients with LOPD under ERT with a 5-year follow-up using mixed linear models. To evaluate quality of life, patients were asked to fill out a specific questionnaire for neuromuscular patients (INQoL). Results: Age at onset of symptoms ranged between 22 and 55 years. FVC-U did not show any significant trend over the follow-up period (mean change: -10.1 L, p=0.21) while PD increased significantly (mean change: 19.3 L, p=0.001). The mean value of global INQoL was 31.2 ±13.5 with weakness as the most affected domain. Global INQoL score was correlated to the change in PD (rho=0.94, p=0.004) but not to FVC-U. Measurements and Main Results: In LOPD patients under ERT, postural drop may reveal a deterioration of diaphragm strength that remains undetected when assessing the upright FVC alone. Besides, it may be related to some aspects of quality of life.

Aims: Arterial hypertension is highly prevalent and difficult to control in patients with obstructive sleep apnea (OSA). High sympathoadrenergic activity is a hallmark physiological phenomenon in OSA. We hypothesized that an antihypertensive drug with inhibitory properties on this activity, such as beta blockers (BBs), may be particularly efficacious in OSA patients. Methods: Hypertensive OSA patients receiving blood pressure-lowing treatment in the European Sleep Apnea Database (ESADA) ( n = 5818, 69% men, age 58 ± 11 years, body mass index 33 ± 7 kg/m 2 , apnea hypopnea index 34 ± 26 events/h) were analyzed. Reported medications [BB, diuretic, renin-angiotensin blocker (RAB), calcium channel blocker (CCB), and centrally acting antihypertensive (CAH)] were classified according to ATC code. Office blood pressure was compared in patients with monotherapy or combination therapy controlling for confounders. Results: Poorly controlled SBP according to the ESC/ESH guidelines was found in 66% of patients. Patients receiving monotherapy with RAB, CCB or CAH had 2.2 (95% CI 1.4–3.0), 3.0 (1.9–4.1) and 3.0 (1.7–4.7) mmHg higher SBP compared with those on BB (adjusted model, P = 0.007, 0.008 and 0.017, respectively). In those with a combination of two antihypertensive drugs, SBP was 5.5 (4.0–7.1), 5.1 (3.7–6.6), 4.3 (2.5–6.1) and 3.1 (1.6–4.6) mmHg higher in those on CCB/RAB, BB/RAB, BB/CCB or diuretic/RAB compared with those on BB/diuretic (adjusted model, P < 0.001, <0.001, 0.018 and 0.036, respectively). Conclusion: Poorly controlled blood pressure was common in OSA patients with antihypertensive medication. Treatment with BB alone or BB in combination with a diuretic was associated with the lowest systolic pressure in this large clinical cohort.