Effect of 12 weeks continuous positive airway pressure on day and night arterial stiffness and blood pressure in patients with type 2 diabetes and obstructive sleep apnea: A randomized controlled trial.

The objective of this study was to evaluate the effect of continuous positive airway pressure treatment on pulse wave velocity and blood pressure in patients with type 2 diabetes and obstructive sleep apnea. A randomized controlled study was performed, including 72 patients with type 2 diabetes and newly diagnosed obstructive sleep apnea recruited from outpatient clinics at three Danish hospitals. The patients were randomized to continuous positive airway pressure for 12 weeks or no continuous positive airway pressure. Office measurements were performed at baseline, 4 weeks and 12 weeks. At baseline and 12 weeks, a 24-hr measurement of pulse wave velocity and blood pressure was performed. No significant change was observed in the primary outcome variable of carotid-femoral pulse wave velocity measured with SphygmoCor. With the Mobil-O-Graph, changes in office pulse wave velocity between the groups were significant: 0.3 m/s; 95% confidence interval, 0.1-0.6; p = .02. The group receiving continuous positive airway pressure had a larger decrease in pulse wave velocity than controls but none of the changes within the groups were significant. No significant change in ambulatory blood pressure was observed in any of the two groups after 12 weeks. In conclusion, continuous positive airway pressure treatment for 12 weeks does not significantly reduce pulse wave velocity or blood pressure in patients with type 2 diabetes and obstructive sleep apnea.

Blood pressure, sympathovagal tone, exercise capacity and metabolic status are linked in Turner syndrome.

OBJECTIVES: We studied cardiac autonomic changes in relation to metabolic factors, body composition and 24-hour ambulatory blood pressure measurements in Turner syndrome patients without known hypertension. DESIGN: Cross sectional. PATIENTS: Participants were 48 TS women and 24 healthy female controls aged over 18 years. METHODS: Short-term power spectral analysis was obtained in supine-standing-supine position. Bedside tests included three conventional cardiovascular reflex tests of heart rate response to standing up, heart rate response to deep breathing and blood pressure response to standing up. Mean heart rate during the last 2 minutes of work was used to calculate the maximal aerobic power (VO2max ). RESULTS: We found a significantly higher mean reciprocal of the heart rate per second (RR) in TS. Testing for interaction between position and status (TS or control), there were highly significant differences between TS and controls in high-frequency (HF) power, the coefficient of component variation (square root of HF power/mean RR) and low-frequency (LF): HF ratio, with a dampened decline in vagal activity among TS during standing. Bedside test showed TS had a significantly higher diastolic BP in the supine position compared to controls, and the adaptive rise in BP, when changing to upright position was reduced. VO2max and self-reported level of physical activity were significantly correlated to systolic ambulatory blood pressure both 24-hour and night diastolic ambulatory blood pressure. CONCLUSION: Vagal tone and modulation of the sympathovagal balance during alteration in body position are impaired in TS. These changes can be risk factors for cardiovascular disease.

Morning blood pressure surge and target organ damage in newly diagnosed type 2 diabetic patients: a cross sectional study.

BACKGROUND: Type 2 diabetic patients display significantly higher incidence of cardiovascular (CV) events including stroke compared to non-diabetics. Morning blood pressure surge (MBPS) and blunted systolic night-day (SND) ratio have been associated with CV events in hypertensive patients. No studies have evaluated MBPS in newly diagnosed diabetic patients or studied the association with vascular target organ damage at this early time point of the diabetes disease. METHODS: Ambulatory blood pressure monitoring was performed in 100 patients with newly diagnosed type 2 diabetes and 100 age and sex matched controls. MBPS and SND-ratio were calculated. Markers of early vascular target organ damage included pulse wave velocity (PWV), white matter lesions (WML) on brain MRI, and urine albumin/creatinine ratio (UAE). RESULTS: No significant differences in MBPS were found between diabetic patients and controls. Neither MBPS or SND-ratio were associated with PWV, UAE or WML in the diabetic group independently of age, gender and 24-h systolic blood pressure. 40.2 % of diabetic patients and 25.8 % of controls were classified as non-dippers (p = 0.03). CONCLUSION: MBPS and SND-ratio are not associated with subclinical markers of vascular target organ damage in our study sample of newly diagnosed type 2 diabetic patients.

Reproducibility of pulse wave analysis and pulse wave velocity in patients with type 2 diabetes.

AIMS: Patients with type 2 diabetes have increased arterial stiffness and a high incidence of cardiovascular disease compared with non-diabetics. Arterial stiffness and central waveforms can be assessed by carotid-femoral pulse wave velocity (PWV) and pulse wave analysis (PWA) using the SphygmoCor device. These methods can potentially improve cardiovascular risk stratification in the future. However, a prerequisite is acceptable reproducibility. The objective of this study was to assess the intra- and inter-observer reproducibility of PWV and PWA indices in patients with type 2 diabetes using the SphygmoCor device. METHODS: Two trained observers (A and B) each undertook two PWA and two carotid-femoral PWV recordings in random order in 20 patients with type 2 diabetes under standardized conditions on the right side of the patients. Observer A also made double recordings on the left side. The mean of the two recordings was used for inter-observer comparison. Data were analyzed by Bland-Altman plots. RESULTS: The mean intra-observer differences (± 2SD) on the right side for observer A and B, respectively, were 0.0 ± 2.8 mmHg and 0.3 ± 3.2 mmHg (aortic systolic blood pressue (BP)), 0.0 ± 1.2 mmHg and 0.1 ± 1.0 mmHg (aortic diastolic BP), - 1.1 ± 3.2% and 1.1 ± 9.6% (central augmentation index (Aix)), - 1.6 ± 6.6% and 0.1 ± 9.0% (Aix normalized to heart rate 75 beats/min (Aix@HR75)) and 0.1 ± 1.8 m/s and 0.0 ± 1.6 m/s (PWV). The mean inter-observer differences (± 2SD) were - 2.6 ± 13.0 mmHg (aortic systolic BP), - 2.1 ± 7.4 mmHg (aortic diastolic BP), - 0.8 ± 8.4% (Aix), - 1.5 ± 7.4% (Aix@HR75) and - 0.3 ± 1.6 m/s (PWV). Left-vs-right comparison showed comparable results (observer A). CONCLUSIONS: PWA and PWV assessed with the SphygmoCor device are characterized by good reproducibility in patients with type 2 diabetes.

Rebound Hypoglycemia and Hyperglycemia in Type 1 Diabetes.

AIMS: The aim was to investigate rebound hypoglycemic and hyperglycemic events, and describe their relation to other glycemic metrics. METHODS: Data from intermittently scanned continuous glucose monitoring were downloaded for 90 days for 159 persons with type 1 diabetes. A hypoglycemic event was defined as glucose <3.9 mmol/l for at least two 15-minute periods. Rebound hypoglycemia (Rhypo) was a hypoglycemic event preceded by glucose >10.0 mmol/l within 120 minutes and rebound hyperglycemia (Rhyper) was hypoglycemia followed by glucose >10.0 mmol/l within 120 minutes. RESULTS: A total of 10 977 hypoglycemic events were identified of which 3232 (29%) were Rhypo and 3653 (33%) were Rhyper, corresponding to a median frequency of 10.1, 2.5, and 3.0 events per person/14 days. For 1267 (12%) of the cases, Rhypo and Rhyper coexisted. The mean peak glucose was 13.0 ± 1.6 mmol/l before Rhypo; 12.8 ± 1.1 mmol/l in Rhyper. The frequency of Rhyper was significantly (P < .001) correlated with Rhypo (Spearman's rho 0.84), glucose coefficient of variation (0.78), and time below range (0.69) but not with time above range (0.12, P = .13). CONCLUSIONS: The strong correlation between Rhyper and Rhypo suggests an individual behavioral characteristic toward intensive correction of glucose excursions.

The Frequency of Intermittently Scanned Glucose and Diurnal Variation of Glycemic Metrics.

BACKGROUND: The relation between the frequency of intermittently scanned continuous glucose monitoring (isCGM) and diurnal variation of time in range (TIR) and time below range (TBR) is unknown. METHOD: A total of 163 persons with type 1 diabetes who used isCGM had glucose data for 60 days downloaded. Mean TIR and median TBR were calculated for 15-minute periods and presented for daytime and nighttime. The values for tertiles of scanning frequency were compared. RESULTS: The 1st tertile (n = 53) of the population scanned <10 times; the 2nd tertile (n = 56) 10-13 times, and the 3rd tertile (n = 54) >13 per 24 hours. TIR (%, mean ± (SD)) increased significantly from the 1st to the 3rd scan tertile both during the day (43.8 ± 14.8, 52.0 ± 12.3, 62.1 ± 12.8) and the night (44.5 ± 17.3, 52.3 ± 18.5, 64.0 ± 13.9; P < .0001). In contrast, TBR (median, (IQR)) was not significantly associated with scan tertiles during daytime (3.5% (1.1-7.8), 4.4% (1.8-6.1), 3.5% (2.1-6.1); P = .85) or nighttime (3.8% (1.4-13.7), 5.0% (1.6-9.6), 5.7% (3.6-10.9); P = .24). In a multiple regression model, a 50% increase in 24-hour scanning frequency was associated with a 7.8 percentage point increase in TIR (95% CI, 5.6-10.0). CONCLUSIONS: Increased scanning frequency was associated with a higher TIR both during daytime and nighttime with no change in TBR.

Real life evaluation of sodium-glucose cotransporter 2 inhibition in type 1 diabetes and the risk of diabetic ketoacidosis.

BACKGROUND: The indication for treatment of type 1 diabetes(T1D) with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin has been withdrawn in Europe likely because of concern for diabetic ketoacidosis (DKA). We calculated the incidence of DKA in people with T1D treated with SGLT2i in Denmark. METHODS: Clinical data from adults with T1D in Denmark were collected from nine outpatient clinics. Electronic health records made the search for DKA accurate. RESULTS: From a population of 10.500 we observed 134 people treated with SGLT2i over a total period of 222 patient-years. Of those 72% were female, mean age (SD) was 51.4 (13.6) years and median duration of treatment (median, IQR) with an SGLT2i were 12.0 (6.0-29.0) months. The incidence of DKA was zero%. CONCLUSION: In 134 people with T1D treated with SGLT2i we found that none of the participants developed DKA during the treatment.

Invasive aortic pulse pressure is not superior to cuff pulse pressure in cardiovascular risk prediction.

OBJECTIVE: Aortic pulse pressure (PP) represents the hemodynamic cardiac and cerebral burden more directly than cuff PP. The objective of this study was to investigate whether invasively measured aortic PP confers additional prognostic value beyond cuff PP for cardiovascular events and death. With increasing age, cuff PP progressively underestimates aortic PP. Whether the prognostic association between cuff PP and outcomes is age-dependent remains to be elucidated. METHODS: Cuff PP and invasively measured aortic PP were recorded in 21 908 patients (mean age 63 years, 58% men, 14% with diabetes) with stable angina pectoris undergoing elective coronary angiography during January 2001--December 2012. Multivariate Cox models were used to assess the association with incident myocardial infarction, stroke, and death. Discrimination was assessed using Harrell's C-index. RESULTS: During a median follow-up period of 3.7 years (range 0.1-10.8 years), 422 strokes, 511 myocardial infarctions, and 1530 deaths occurred. Both cuff and aortic PP were associated with stroke, myocardial infarction, and death in crude analyses. However, only cuff PP remained associated with stroke (hazard ratio per 10 mmHg, 1.06 (95% confidence interval (CI) 1.01--1.12)] and myocardial infarction [hazard ratio per 10 mmHg 1.05 (95% CI 1.01--1.11)] in multivariate Cox models. Both cuff and aortic PP lost significance as predictors of death in multivariate models. Age did not modify the prognostic association between cuff PP and stroke, myocardial infarction, and death. CONCLUSION: Invasively measured aortic PP did not add prognostic information about cardiovascular outcomes and death beyond cuff PP in patients with stable angina pectoris.

Thoracic aortopathy in Turner syndrome and the influence of bicuspid aortic valves and blood pressure: a CMR study.

BACKGROUND: To investigate aortic dimensions in women with Turner syndrome (TS) in relation to aortic valve morphology, blood pressure, karyotype, and clinical characteristics. METHODS AND RESULTS: A cross sectional study of 102 women with TS (mean age 37.7; 18-62 years) examined by cardiovascular magnetic resonance (CMR- successful in 95), echocardiography, and 24-hour ambulatory blood pressure. Aortic diameters were measured by CMR at 8 positions along the thoracic aorta. Twenty-four healthy females were recruited as controls. In TS, aortic dilatation was present at one or more positions in 22 (23%). Aortic diameter in women with TS and bicuspid aortic valve was significantly larger than in TS with tricuspid valves in both the ascending (32.4 +/- 6.7 vs. 26.0 +/- 4.4 mm; p < 0.001) and descending (21.4 +/- 3.5 vs. 18.8 +/- 2.4 mm; p < 0.001) aorta. Aortic diameter correlated to age (R = 0.2 - 0.5; p < 0.01), blood pressure (R = 0.4; p < 0.05), a history of coarctation (R = 0.3; p = 0.01) and bicuspid aortic valve (R = 0.2-0.5; p < 0.05). Body surface area only correlated with descending aortic diameter (R = 0.23; p = 0.024). CONCLUSIONS: Aortic dilatation was present in 23% of adult TS women, where aortic valve morphology, age and blood pressure were major determinants of the aortic diameter.

Ambulatory arterial stiffness index in Turner syndrome: the impact of sex hormone replacement therapy.

BACKGROUND: Morbidity and mortality from congenital and acquired cardiovascular (CV) disease is increased in Turner syndrome (TS), where traditional indices of CV risk are widely present but the single most common feature remains estrogen deficiency. AIM: To investigate CV risk in TS as expressed by the widely available ambulatory arterial stiffness index (AASI) and the impact of female sex hormone replacement therapy (HRT) hereon. METHODS: TS women (n = 26) were examined following HRT washout and again during 6 months of HRT. Age-matched healthy female controls (n = 24) were examined once. 24-Hour ambulatory blood pressures, AASI in addition to metabolic and anthropometric indices of CV risk were measured. RESULTS: The relatively tachycardic TS women had higher systolic and diastolic blood pressures. HRT reduced diastolic blood pressures with an increase in physical fitness, worsening of glucose tolerance, and a reduction in high-density lipoprotein. AASI was significantly elevated in TS when compared to controls (0.36 (0.02) vs. 0.26 (0.03), p = 0.01) but unaffected by HRT. Major explanatory variables to AASI were status (being TS or not), age, and diurnal pulse variability. CONCLUSION: AASI was elevated in TS, possibly indicating elevated CV risk with no impact of short-term HRT.

Pulse pressure lowering effect of dual blockade with candesartan and lisinopril vs. high-dose ACE inhibition in hypertensive type 2 diabetic subjects: a CALM II study post-hoc analysis.

BACKGROUND: Elevated pulse pressure (PP) is strongly associated with micro- and macrovascular complications in type 2 diabetic patients. We examined the effect of 12 months of dual blockade with candesartan and lisinopril vs. high-dose lisinopril monotherapy on ambulatory PP in hypertensive type 2 diabetic patients from the CALM (Candesartan and Lisinopril Microalbuminuria Trial) II study. METHODS: The CALM II study was a 12-month prospective, randomized, parallel-group, double-masked study that included 75 type 1 and type 2 diabetic subjects with hypertension. Participants were randomized for treatment with either high-dose lisinopril (40 mg once daily (o.d.)) or for dual blockade treatment with candesartan (16 mg o.d.) and lisinopril (20 mg o.d.). In this article, we present data from the post-hoc subgroup of 51 type 2 diabetic subjects who completed the full 12-month study period with successful ambulatory blood pressure (BP) measurements at both baseline and follow-up visits. RESULTS: Baseline 24-h BP values were similar in the two groups (24-h systolic BP (SBP) 130 +/- 12 vs. 127 +/- 9, 24-h diastolic BP (DBP) 77 +/- 8 vs. 74 +/- 7, and 24-h PP 53 +/- 8 vs. 53 +/- 7 mm Hg, for the lisinopril and dual blockade groups, respectively, P > 0.2 for all). Compared with lisinopril monotherapy, dual blockade treatment caused a highly significant reduction in 24-h PP levels (-5 +/- 5 mm Hg, P = 0.003), albeit the difference in the BP lowering effect between the treatment groups did not differ significantly for 24-h systolic (P = 0.21) or diastolic (P = 0.49) BP. Dual blockade treatment significantly lowered 24-h SBP (-5 +/- 11 mm Hg, P = 0.03), but not 24-h DBP (-2 +/- 7 mm Hg, P = 0.29), whereas in the lisinopril group, the opposite effect was observed (24-h SBP -1 +/- 9 mm Hg, P = 0.45, 24-h SBP -3 +/- 7 mm Hg, P = 0.03). CONCLUSIONS: Twelve months of dual blockade with candesartan and lisinopril significantly reduced PP when compared with high-dose monotherapy with lisinopril. Larger studies are needed to confirm this observation, and to evaluate whether this effect translates into a greater degree of end-organ protection from dual blockade treatment than from conventional angiotensin-converting enzyme (ACE) inhibition.

Effects of renal denervation on coronary flow reserve and forearm dilation capacity in patients with treatment-resistant hypertension. A randomized, double-blinded, sham-controlled clinical trial.

BACKGROUND: Microvascular impairment is well documented in hypertension. We investigated the effect of renal sympathetic denervation (RDN) on cardiac and peripheral microvasculature in patients with treatment-resistant essential hypertension (TRH). METHODS: A randomized, single centre, double-blinded, sham-controlled clinical trial. Fifty-eight patients with TRH (ambulatory systolic BP (ASBP) ≥ 145mmHg) despite stable treatment were randomized to RDN or SHAM. RDN was performed with the unipolar Medtronic Flex catheter. Coronary flow reserve (CFR) and coronary- and forearm minimum vascular resistance (C-Rmin and F-Rmin) were determined using transthoracic Doppler echocardiography and F-Rmin with venous occlusion plethysmography at baseline and at six-months follow-up. RESULTS: RDN was performed with 5.3±0.2 lesions in the right renal artery and 5.4±0.2 lesions in the left. Baseline ASBP was 152±2mmHg (RDN, n=29) and 154±2mmHg (SHAM, n=29). Similar reductions in MAP were seen at follow up (-3.5±2.0 vs. -3.2±1.8, P=0.92). Baseline CFR was 2.9±0.1 (RDN) and 2.4±0.1 (SHAM), with no significant change at follow-up (0.2±0.2 vs. -0.1±0.2, P=0.57). C-Rmin was 1.9±0.3 (RDN) and 2.7±0.6 (SHAM) (mmHgmin/ml pr. 100g) and did not change significantly (0.3±0.5 vs. -0.4±0.8, P=0.48). F-Rmin was 3.6±0.2 (RDN) and 3.6±0.3 (SHAM) (mmHgmin/ml pr. 100ml tissue) and unchanged at follow-up (4.2±0.4 vs. 3.8±0.2, P=0.17). Left ventricular mass index was unchanged following RDN (-4±7 (RDN) vs. 3±5 (SHAM) (g/m2) P=0.38). CONCLUSION: The current study does not support positive effects of RDN on microvascular impairment in TRH.

Evaluation of interarm blood pressure differences using the Microlife WatchBP Office in a clinical setting.

OBJECTIVE: The aim of this study was to evaluate the usefulness of Microlife WatchBP Office and the effect of increasing the number of measurements in the clinical evaluation of systolic interarm difference (IAD). PATIENTS AND METHODS: Office blood pressure was measured simultaneously on both arms in 339 patients (85% diabetic) using the Microlife WatchBP Office, a fully automatic, oscillometric device. The patients included were all scheduled for ambulatory blood pressure measurement at the outpatient clinic of endocrinology at Silkeborg Regional Hospital, Denmark. Two successive sets of three individual measurements were made. A statistical analysis of variance was carried out on the measurements. RESULTS: In the first set of measurements, the mean IAD was -0.3 mmHg and the prevalence of IAD greater than or equal to 10 mmHg was 9.1%. Only 7.6% of the patients with an IAD less than 10 mmHg in the first set of measurements had an IAD greater than or equal to 10 mmHg in the second set of measurements. The 95% limits of agreement for the mean IAD for a single set of three measurements were ±13.16 mmHg. The probability of detecting an IAD more than 10 mmHg only increased slightly with an increasing number of measurements. CONCLUSION: A single set of triplicate measurements using Microlife WatchBP is an acceptable method for evaluating IAD as more measurements do little to improve the probability of detecting an IAD more than 10 mmHg because of high intraindividual variation.

Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study.

OBJECTIVE: To assess and compare the long-term effects of the combination of candesartan and lisinopril with high-dose lisinopril on systolic blood pressure in patients with hypertension and diabetes. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, parallel-group, double-blind, double-dummy study with a 12-month follow-up. Drug therapy was either lisinopril 40 mg once daily or dual-blockade treatment with candesartan 16 mg once daily and lisinopril 20 mg once daily. The study comprised 75 type 1 and type 2 diabetic patients aged 35-74 years. The main outcome measures were seated and 24-h ambulatory systolic blood pressure. RESULTS: Reduction in systolic blood pressure (24-h systolic blood pressure) reduction was obtained in both treatment arms (mean reduction at final follow-up: dual blockade 6 mmHg vs. lisinopril 2 mmHg), but no significant difference was found between dual-blockade and lisinopril 40 mg once daily (P = 0.10). Both treatments were generally well tolerated, and similar low rates of side effects were found in the two groups. CONCLUSIONS: There was no statistically significant difference between lisinopril 40 mg once daily and lisinopril 20 mg in combination with candesartan 16 mg once daily in reducing systolic blood pressure in hypertensive patients with diabetes.

Reduced Subendocardial Viability Ratio Is Associated With Unfavorable Cardiovascular Risk Profile in Women With Short Duration of Type 2 Diabetes.

BACKGROUND: The pathophysiological perturbations underlying the unfavorable cardiovascular prognosis in women with type 2 diabetes (T2DM) remain elusive. Low subendocardial viability ratio (SEVR), an index of myocardial oxygen supply and demand, has been associated with intermediate cardiovascular risk markers and cardiovascular mortality in various populations. However, whether SEVR is associated with sex and cardiovascular risk markers in patients with T2DM remains to be clarified. METHODS: We examined 86 T2DM patients (mean age 59±10 years, 47% women, median diabetes duration 1.9 (range 0.2-5.0) years) and 86 sex- and age-matched control subjects in a cross-sectional study. SEVR was noninvasively assessed by tonometry and markers of cardiovascular risk by carotid-femoral pulse wave velocity (PWV), homeostasis model assessment of insulin resistance (HOMA2-IR), C-reactive protein, urinary albumin/creatinine ratio, and heart rate variability. RESULTS: Women with diabetes had significantly lower SEVR compared to both men with diabetes (161% ± 26% vs. 178% ± 32%, P < 0.01), women without diabetes (185% ± 24%, P < 0.001), and men without diabetes (188% ± 28%, P < 0.001). The differences remained significant after adjustment for age, systolic blood pressure, heart rate, diabetes, and smoking. SEVR was associated with PWV, HOMA2-IR, C-reactive protein, and reduced heart rate variability in patients and control subjects, but the associations became nonsignificant after adjustment for heart rate. CONCLUSIONS: SEVR is reduced in women with short duration of T2DM and associated with cardiovascular risk markers. The latter association seems to be at least partly mediated via heart rate. We hypothesize that reduced SEVR may contribute to the unfavorable cardiovascular prognosis in women with diabetes.

Invasively Measured Aortic Systolic Blood Pressure and Office Systolic Blood Pressure in Cardiovascular Risk Assessment: A Prospective Cohort Study.

Aortic systolic blood pressure (BP) represents the hemodynamic cardiac and cerebral burden more directly than office systolic BP. Whether invasively measured aortic systolic BP confers additional prognostic value beyond office BP remains debated. In this study, office systolic BP and invasively measured aortic systolic BP were recorded in 21 908 patients (mean age: 63 years; 58% men; 14% with diabetes mellitus) with stable angina pectoris undergoing elective coronary angiography during January 2001 to December 2012. Multivariate Cox models were used to assess the association with incident myocardial infarction, stroke, and death. Discrimination and reclassification were assessed using Harrell's C and the Continuous Net Reclassification Index. Data were analyzed with and without stratification by diabetes mellitus status. During a median follow-up period of 3.7 years (range: 0.1-10.8 years), 422 strokes, 511 myocardial infarctions, and 1530 deaths occurred. Both office and aortic systolic BP were associated with stroke in patients with diabetes mellitus (hazard ratio per 10 mm Hg, 1.18 [95% confidence interval, 1.07-1.30] and 1.14 [95% confidence interval, 1.05-1.24], respectively) and with myocardial infarction in patients without diabetes mellitus (hazard ratio, 1.07 [95% confidence interval, 1.02-1.12] and 1.05 [95% confidence interval, 1.01-1.10], respectively). In models including both BP measurements, aortic BP lost statistical significance and aortic BP did not confer improvement in either C-statistics or net reclassification analysis. In conclusion, invasively measured aortic systolic BP does not add prognostic information about cardiovascular outcomes and all-cause mortality compared with office BP in patients with stable angina pectoris, either with or without diabetes mellitus.

Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

BACKGROUND: Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. METHOD: We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). RESULTS: We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ±â€Š12 mmHg (RDN) and 159 ±â€Š14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ±â€Š18.8 mmHg (RDN) vs. -6.0 ±â€Š13.5 mmHg (SHAM)] and at 6 months [-6.1 ±â€Š18.9 mmHg (RDN) vs. -4.3 ±â€Š15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ±â€Š2.7 (RDN) vs. 7.0 ±â€Š2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. CONCLUSION: Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Assessment of central blood pressure in patients with type 2 diabetes: a comparison between SphygmoCor and invasively measured values.

BACKGROUND: The SphygmoCor is used for noninvasive assessment of ascending aortic blood pressure (BP). However, the validity of the SphygmoCor transfer function has not been tested in an exclusively type 2 diabetic patient sample. Calibration with systolic (SBP) and diastolic (DBP) brachial BP has previously been associated with substantial imprecision of central BP estimates. We hypothesized that different noninvasive calibration strategies might improve the accuracy of the estimated ascending aortic BPs. METHODS: In 34 patients with type 2 diabetes we estimated ascending aortic SBP and DBP using the SphygmoCor device and compared these data with invasively recorded data. The validity of the transfer function was assessed by calibrating with invasively recorded DBP and mean BP (MBP). The influence of noninvasive calibration strategies was assessed by calibrating with brachial oscillometric SBP+DBP vs. DBP+MBP using a form factor (ff) of 0.33 and 0.40, respectively. RESULTS: When calibrating with invasive BP, the difference between estimated and invasively measured ascending aortic SBP and DBP was -2.3±5.6/1.0±0.9 mm Hg. When calibrating with oscillometric brachial BPs, the differences were -9.6±8.1/14.1±6.2 mm Hg (calibration with SBP and DBP), -8.3±11.7/13.9±6.1 mm Hg (DBP and MBP; ff = 0.33), and 1.9±12.2/14.1±6.2 mm Hg (DBP and MBP; ff = 0.40), respectively. Calibration with the average of 3 brachial BPs did not improve accuracy. CONCLUSIONS: The SphygmoCor transfer function seems valid in patients with type 2 diabetes. Noninvasive calibration with DBP and MBP (ff = 0.40) enables accurate estimation of mean ascending aortic SBP at the group level. However, the wide limits of agreement indicate limited accuracy in the individual patient. CLINICAL TRIALS REGISTRATION: Clinical Trials No. NCT01538290.

A plea for consistent reliability in ambulatory blood pressure monitoring: an unusual case of software error in Spacelabs Report Management System 92506.

OBJECTIVE: Ambulatory blood pressure monitors are subject to extensive validation protocols, but no international guidelines on the software processing the collected raw data exist. Hence, there seems to be little or no control of ambulatory blood pressure monitoring (ABPM) software with respect to errors. In this paper, we wish to point out an important error in Spacelabs Report Management System 92506 software. METHODS: By chance, we noticed discrepancies in the Spacelabs Report Management System 92506 hourly average tabular as shown on-screen and on printout. To exclude the possibility of a random error, 97 ABPM reports were evaluated. In a random patient, we calculated the hourly averages by the arithmetic mean from all measurements. Similarly, the summary average of 24 h, daytime and night-time blood pressure was calculated both by the arithmetic mean of all measurements and by the mean of hourly averages in the respective periods. RESULTS: Evaluation of ABPM reports showed errors in 89 out of 97 (92%). In a random patient, the numerical difference between printout and on-screen hourly averages was considerable, ranging from -37 to 18 mmHg systolic and from -16 to 10 mmHg diastolic. Calculation on the basis of raw data established that on-screen hourly average tabular was correct, whereas printout values were erroneous. The erroneous values were also found in the exported hourly average tabular. CONCLUSION: If researchers base calculations on the use of erroneous data from printout or exported hourly average tabular, the results and hence the conclusions may be wrong. Focus on ABPM software is warranted.