The effects of topiroxostat on vascular function in patients with hyperuricemia

Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol and febuxostat, inhibit the catalysis of serum uric acid (SUA) synthesis. In doing so, they are thought to improve vascular endothelial function in patients with hyperuricemia and cardiovascular risk by reducing increases in SUA and reactive oxygen species levels. We performed a retrospective cohort study to evaluate the effects of topiroxostat, a novel XOR inhibitor, on vascular function measured by flow‐mediated dilation (FMD) on ultrasonography. In total, 23 patients with hyperuricemia were enrolled. After approximately 8 weeks, topiroxostat was associated with a significant increase in the peak percentage change in diameter (∆FMD) from 4.53% ± 2.09% to 5.54% ± 3.08% (P = .045). It also significantly reduced the SUA levels from 7.31 ± 1.43 to 5.44 ± 1.11 mg/dL (P < .001). Although further studies are needed to validate these results, it appears that topiroxostat improves vascular endothelial function in patients with hyperuricemia.     

Association of urinary sodium/potassium ratio with structural and functional vascular changes in non‐diabetic hypertensive patients

Studies aiming to associate the sodium/potassium (Na/K) ratio with hypertension use 24‐hour urinary excretion as a daily marker of ingestion. The objective of this study was to evaluate the association between urinary Na/K ratio and structural and functional vascular alterations in non‐diabetic hypertensive patients. In hypertensive patients (n = 72), aged between 40 and 70 years, both sexes (61% women), in use of hydrochlorothiazide, we measured blood pressure, 24‐hour urine sample collection, assessment of carotid‐femoral pulse wave velocity (cf‐PWV, Complior), central hemodynamic parameters (SphygmoCor), and post‐occlusive reactive hyperemia (PORH). The participants were divided according to the tertile of 24‐hour urinary Na/K ratio. Each group contained 24 patients. Systolic blood pressure was higher in T2 (133 ± 9 vs 140 ± 9 mmHg, P = .029). C‐reactive protein (CRP) presented higher values in T3 as compared to T1 [0.20(0.10‐0.34) vs 1.19 (0.96‐1.42) mg/dL, P < .001]. Higher values in T3 were also observed for aortic systolic pressure (aoSP) [119(114‐130) vs 135(125‐147) mmHg, P = .002] and cf‐PWV (9.2 ± 1.6 vs 11.1 ± 1.5 m/s, P < .001). The urinary Na/K ratio presented significant correlations with proteinuria (r = .27, P = .023), CRP (r = .77, P < .001), cf‐PWV (r = .41, P < .001), and post‐occlusive reactive hyperemia on cutaneous vascular conductance (PORH CVC) (r = −.23, P = .047). By multivariate linear regression, it was detected an independent and significant association of cf‐PWV with urinary Na/K ratio (R ² = 0.17, P < .001) and PORH CVC with CRP (R ² = 0.30, P = .010). Our data indicated that increased urinary Na/K ratio in non‐diabetic hypertensive patients was associated with higher degree of inflammation, raised peripheral and central pressure levels, and changes suggestive of endothelial dysfunction and arterial stiffness.     

Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized,double‐blind, 8‐week study

A majority of patients with hypertension fail to achieve blood pressure (BP) control despite treatment with commonly prescribed drugs. This randomized, double‐blind phase III trial assessed the superiority of sacubitril/valsartan 200 mg (97/103 mg) to continued olmesartan 20 mg in reducing ambulatory systolic BP after 8‐week treatment in patients with mild to moderate essential hypertension uncontrolled with olmesartan 20 mg alone. A total of 376 patients were randomized to receive either sacubitril/valsartan (n = 188) or olmesartan (n = 188). Superior reductions in 24‐hour mean ambulatory systolic BP were observed in the sacubitril/valsartan group vs the olmesartan group (−4.3 mm Hg vs −1.1 mm Hg, P < .001). Reductions in 24‐hour mean ambulatory diastolic BP and pulse pressure and office systolic BP and diastolic BP were significantly greater with sacubitril/valsartan vs olmesartan (P < .014). A greater proportion of patients achieved BP control with sacubitril/valsartan vs olmesartan. The overall incidence of adverse events was comparable between the groups. Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20 mg.     

Acupuncture for patients with mild hypertension: A randomized controlled trial

Acupuncture may be beneficial for patients with mild hypertension, but the evidence is not convincing. We aimed to examine the effect of acupuncture on blood pressure (BP) reduction in patients with mild hypertension. We conducted a multicenter, single‐blind, sham‐controlled, randomized trial in eleven hospitals in China. The trial included 428 patients with systolic blood pressure (SBP) from 140 to 159 mm Hg and/or with diastolic blood pressure (DBP) from 90 to 99 mm Hg. The patients were randomly assigned to receive 18 sessions of affected meridian acupuncture (n = 107) or non‐affected meridian acupuncture (n = 107) or sham acupuncture (n = 107) during 6 weeks, or to stay in a waiting‐list control (n = 107). All patients received 24‐hour ambulatory blood pressure monitoring at weeks 6, 9, and 12. We included 415 participants in the intention‐to‐treat analysis. The two acupuncture groups were pooled in the analysis, since they had no difference in all outcomes. SBP decreased at week 6 in acupuncture group vs sham acupuncture vs waiting‐list group (7.2 ± 11.0 mm Hg vs 4.1 ± 11.5 mm Hg vs 4.1 ± 13.2 mm Hg); acupuncture was not superior to sham acupuncture (mean difference 2.7 mm Hg, 95% CI 0.4 to 5.9, adjusted P = 0.103) or waiting‐list control (2.9 mm Hg, 95% CI −0.2 to 6.0, adjusted P = 0.078). However, acupuncture was superior to sham acupuncture (3.3 mm Hg, 95% CI 0.2 to 6.3, adjusted P = 0.035) and waiting‐list control (4.8 mm Hg, 95% CI 1.8 to 7.8, P < 0.001) at week 9. Acupuncture had a small effect size on the reduction of BP in patients with mild hypertension.     

Impact of daily glucose fluctuations on cardiovascular outcomes after percutaneous coronary intervention for patients with stable coronary artery disease undergoing lipid-lowering therapy

Aims/IntroductionGlucose fluctuation (GF) is a residual risk factor for coronary artery disease (CAD). We investigated whether GF influenced clinical outcomes and progression of coronary stenosis in stable CAD patients.Materials and MethodsIn this prospective study, 101 consecutive lipid‐controlled stable CAD patients underwent percutaneous coronary intervention were enrolled, and GF was expressed as the mean amplitude of glycemic excursion (MAGE) obtained by continuous glucose monitoring before the procedure was evaluated. At 9 months after enrollment, culprit and non‐culprit (mild‐to‐moderate stenosis without ischemia) lesions were serially assessed by angiography. Cardiovascular events (CVE) consisting of cardiovascular death, non‐fatal myocardial infarction or ischemia‐driven revascularization during 2‐year follow up, rapid progression in non‐culprit lesions (defined as ≥10% luminal narrowing progression in lesions with stenosis ≥50%, ≥30% luminal narrowing progression in non‐culprit lesions with stenosis <50% or normal segment, or progression to total occlusion) were evaluated.ResultsCVE occurred in 25 patients, and MAGE was significantly higher in the CVE group (76.1 ± 24.8 mg/dL vs 59.3 ± 23.7 mg/dL; P = 0.003). Multivariate analysis showed that MAGE was an independent predictor of CVE (odds ratio 1.027, 95% confidence interval 1.008–1.047; P = 0.005). The optimal MAGE value to predict CVE was 70.7 mg/dL (area under the curve 0.687, 95% confidence interval 0.572–0.802; P = 0.005). Furthermore, MAGE was independently associated with rapid progression, and with the luminal narrowing progression in all non‐culprit lesions (r = 0.400, P < 0.05).ConclusionsDaily GF might influence future CVE in lipid‐controlled stable CAD patients.     

Poor sleep quality is associated with cardiac autonomic dysfunction in treated hypertensive men

Hypertensives present cardiac autonomic dysfunction. Reduction in sleep quality increases blood pressure (BP) and favors hypertension development. Previous studies suggested a relationship between cardiovascular autonomic dysfunction and sleep quality, but it is unclear whether this association is present in hypertensives. Thus, this study evaluated the relationship between sleep quality and cardiac autonomic modulation in hypertensives. Forty‐seven middle‐aged hypertensive men under consistent anti‐hypertensive treatment were assessed for sleep quality by the Pittsburgh Sleep Quality Index (PSQI—higher score means worse sleep quality). Additionally, their beat‐by‐beat BP and heart rate (HR) were recorded, and cardiac autonomic modulation was assessed by their variabilities. Mann‐Whitney and t tests were used to compare different sleep quality groups: poor (PSQI > 5, n = 24) vs good (PSQI ≤ 5, n = 23), and Spearman’s correlations to investigate associations between sleep quality and autonomic markers. Patients with poor sleep quality presented lower cardiac parasympathetic modulation (HR high‐frequency band = 26 ± 13 vs 36 ± 15 nu, P = .03; HR total variance = 951 ± 1373 vs 1608 ± 2272 ms², P = .05) and cardiac baroreflex sensitivity (4.5 ± 2.3 vs 7.1 ± 3.7 ms/mm Hg, P = .01). Additionally, sleep quality score presented significant positive correlation with HR (r = +0.34, P = .02) and negative correlations with HR high‐frequency band (r = −0.34, P = .03), HR total variance (r = −0.35, P = .02), and cardiac baroreflex sensitivity (r = −0.42, P = .01), showing that poor sleep quality is associated with higher HR and lower cardiac parasympathetic modulation and baroreflex sensitivity. In conclusion, in treated hypertensive men, poor sleep quality is associated with cardiac autonomic dysfunction.     

Improvement in health‐related quality of life after renal sympathetic denervation in real‐world hypertensive patients: 12‐month outcomes in the Global SYMPLICITY Registry

Renal denervation has been shown to reduce blood pressure in patients with uncontrolled hypertension, but less is known about its impact on quality of life. This analysis evaluated 12‐month blood pressure and quality of life outcomes in 934 patients from the Global SYMPLICITY Registry who completed the EuroQoL five‐dimensions three‐level questionnaire (EQ‐5D‐3L). At baseline, 32% of patients reported anxiety/depression and 48% reported pain/discomfort. At 12 months (n=496), office and 24‐hour ambulatory systolic blood pressure were reduced by 13.9±26.6 and 7.7±19.3 mm Hg, respectively, and 8% (P<.001) more patients reported no problems in anxiety/depression. Furthermore, numerically more patients reported no problems in pain/discomfort (4%, P=.08). Perceived health‐related quality of life (visual analog scale) improved from baseline to 12 months (68±18 vs 73±17, P<.001), and the improvement was largest among patients with severe anxiety/depression at baseline (50±24 vs 64±22, P=.005 [n=32]). In this analysis, renal denervation was associated with a significant improvement in health‐related quality of life, particularly anxiety/depression.     

Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: A randomized,double‐blind, 8‐week study

This study assessed the efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril/valsartan vs olmesartan in Asian patients with mild‐to‐moderate hypertension. Patients (N = 1438; mean age, 57.7 years) with mild‐to‐moderate hypertension were randomized to receive once daily administration of sacubitril/valsartan 200 mg (n = 479), sacubitril/valsartan 400 mg (n = 473), or olmesartan 20 mg (n = 486) for 8 weeks. The primary endpoint was reduction in mean sitting systolic blood pressure (msSBP) from baseline with sacubitril/valsartan 200 mg vs olmesartan 20 mg at Week 8. Secondary endpoints included msSBP reduction with sacubitril/valsartan 400 mg, and reductions in clinic and ambulatory BP and pulse pressure (PP) vs olmesartan. In addition, changes in msBP from baseline in the Chinese subpopulation, elderly (≥65 years), and in patients with isolated systolic hypertension (ISH) were assessed. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP than olmesartan 20 mg at Week 8 (between‐treatment difference: −2.33 mm Hg [95% confidence interval (CI) −4.00 to −0.66 mm Hg], P < 0.05 for non‐inferiority and superiority). Greater reductions in msSBP were also observed with sacubitril/valsartan 400 mg vs olmesartan 20 mg (−3.52 [−5.19 to −1.84 mm Hg], P < 0.001 for superiority). Similarly, greater reductions in msBP were observed in the Chinese subpopulation, in elderly patients, and those with ISH. In addition, both doses of sacubitril/valsartan provided significantly greater reductions from baseline in nighttime mean ambulatory BP vs olmesartan. Treatment with sacubitril/valsartan 200 or 400 mg once daily is effective and provided superior BP reduction than olmesartan 20 mg in Asian patients with mild‐to‐moderate hypertension and is generally safe and well tolerated.     

Effects of aerobic interval training on arterial stiffness and microvascular function in patients with metabolic syndrome

The authors determined the effect of high‐intensity aerobic interval training on arterial stiffness and microvascular dysfunction in patients with metabolic syndrome with hypertension. Applanation tonometry was used to measure arterial stiffness and laser Doppler flowmetry to assess microvascular dysfunction before and after 6 months of stationary cycling (training group; n = 23) in comparison to a group that remained sedentary (control group; n = 23). While no variable improved in controls, hypertension fell from 79% (59%–91%) to 41% (24%–61%) in the training group, resulting in lower systolic and diastolic pressures than controls (−12 ± 3 and −6 ± 2 mm Hg, P < .008). Arterial stiffness declined (−17% augmentation index, P = .048) and reactive hyperemia increased (20%, P = .028) posttreatment in the training group vs controls. Blood constituents associated with arterial stiffness and a prothrombotic state (high‐sensitivity C‐reactive protein, fibrinogen, platelets, and erythrocytes) remained unchanged in the training and control groups. In summary, 6 months of an intense aerobic exercise program reduced both arterial stiffness and microvascular dysfunction in patients with metabolic syndrome despite unchanged blood‐borne cardiovascular risk factors. Training lowers blood flow resistance in central and peripheral vascular beds in a coordinated fashion, resulting in clinically relevant reductions in hypertension.     

Admission hyperglycemia predicts poorer short‐ and long‐term outcomes after primary percutaneous coronary intervention for ST‐elevation myocardial infarction

Aims/Introduction

Admission hyperglycemia is associated with poor outcome in patients with myocardial infarction. The present study evaluated the relationship between admission glucose level and other clinical variables in patients with ST‐elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Materials and Methods

The 959 consecutive STEMI patients undergoing primary PCI were divided into five groups based on admission glucose levels of <100, 100–139, 140–189, 190–249 and ≥250 mg/dL. Their short‐ and long‐term outcomes were compared.

Results

Higher admission glucose levels were associated with significantly higher in‐hospital morbidity and mortality, the overall mortality rate at follow up, and the incidence of reinfarction or heart failure requiring admission or leading to mortality at follow up. The odds ratios (95% confidence interval) for in‐hospital morbidity, in‐hospital mortality, mortality at follow up and re‐infarction or heart failure or mortality at follow up of patients with admission glucose levels ≥190 mg/dL, compared with those with admission glucose levels <190 mg/dL, were 2.12 (1.3–3.4, P = 0.001), 2.74 (1.4–5.5, P = 0.004), 2.52 (1.2–5.1, P = 0.01) and 1.70 (1.03–2.8, P = 0.04), respectively. Previously non‐diabetic patients with admission glucose levels ≥250 mg/dL had significantly higher in‐hospital morbidity or mortality (44 vs 70%, P = 0.03). Known diabetic patients had higher rates of reinfarction, heart failure or mortality at follow up in the 100–139 mg/dL (8 vs 27%, P = 0.04) and 140–189 mg/dL (11 vs 26%, P = 0.02) groups.

Conclusions

Admission hyperglycemia, especially at glucose levels ≥190 mg/dL, is a predictor of poor prognosis in STEMI patients undergoing primary PCI.     

A randomized multicenter study on ambulatory blood pressure and arterial stiffness in patients treated with valsartan/amlodipine or nifedipine GITS

In a pre‐specified subgroup analysis of a 12‐week randomized multicenter study, we investigated effects of valsartan/amlodipine 80/5 mg single‐pill combination (n = 75) and nifedipine GITS 30 mg (n = 75) on ambulatory blood pressure (BP) and arterial stiffness assessed by brachial‐ankle pulse wave velocity (PWV) in patients with uncontrolled hypertension. At week 12, the between‐treatment mean differences in systolic/diastolic BP were smaller for 24‐hour and daytime (–2.1/–1.7 and −2.0/−1.5 mm Hg, respectively, P ≥ 0.22) but greater (P < 0.01) for nighttime (–4.0/‐2.8 mm Hg, P ≤ 0.09), especially in sustained uncontrolled hypertension (−5.0/−4.1 mm Hg, P ≤ 0.04) and non‐dippers (−6.5/−3.7 mm Hg, P ≤ 0.07), in favor of valsartan/amlodipine. At week 12, PWV was significantly reduced from baseline by valsartan/amlodipine (n = 59, P < 0.0001) but not nifedipine (n = 59, P = 0.06). The changes in PWV were significantly associated with that in ambulatory systolic BP and pulse pressure in the nifedipine (P ≤ 0.0008) but not valsartan/amlodipine group (P ≥ 0.57), with a significant interaction (P ≤ 0.045). The valsartan/amlodipine combination was more efficacious than nifedipine GITS in lowering nighttime BP in sustained uncontrolled hypertension and non‐dippers, and in lowering arterial stiffness independent of BP lowering.     

Meaning of upper limit of normal range of post‐load 1‐h plasma glucose level defined by oral glucose tolerance test in Japanese subjects

Aims/Introduction

To identify upper limit post‐load 1‐h plasma glucose (1‐h PG) after 75‐g oral glucose test in a Japanese population.

Materials and Methods

A total of 918 subjects were enrolled. We divided the subjects into two groups: normal 2‐h post‐load plasma glucose (2‐h PG; <140 mg/dL) and impaired 2‐h PG group (≥140 mg/dL).

Results

A total of 417 subjects had normal 2‐h PG and 501 had impaired 2‐h PG. The receiver operating characteristic (ROC) curve showed that the optimal cut‐off value of 1‐h PG was 179 mg/dL (area under ROC curve = 0.89), providing that the sensitivity, specificity, and positive and negative predictive value were 85, 79, 82 and 83%, respectively. The subjects with 1‐h PG < 179 mg/dL consisted of 0.5% diabetes and 99.5% non‐diabetes, whereas those with 1‐h PG ≥ 179 mg/dL consisted of 26.9% diabetes and 73.1% non‐diabetes (P < 0.01). Furthermore, there was a significant correlation between 1‐h PG and 2‐h PG (r² = 0.57, P < 0.01).

Conclusions

These data suggested that 179 mg/dL is the upper limit of the normal range of post‐load of 1‐h PG in a Japanese population. Thus, the subjects with 1‐h PG ≥ 179 mg/dL might be at risk of developing future diabetes. Therefore, appropriate prospective study should be carried out to test this hypothesis.     

Association between retinal arterial narrowing and left ventricular diastolic dysfunction in masked hypertensives

Morphological change in retinal vessel diameters has been reported to be associated with negative cardiovascular outcomes, but its association with left ventricular diastolic dysfunction (LVDD) is not clear. This study aimed to examine the association between echocardiographic markers of LVDD and retinal vascular diameters, in untreated masked hypertension (MH). In this observational study, 105 MH patients without other cardiovascular risks were included (mean age 48.4 ± 5.7, female 72.4%). All individuals underwent extensive clinical and laboratory investigations, including echocardiography, ambulatory blood pressure monitoring, and retinal vascular diameters measured by optical coherence tomography. In the group, LVDD was diagnosed in 36 participants evaluated by left ventricular volume index, E/A and E/e’ ratio. Compared to non‐LVDD, LVDD subjects displayed narrower retinal arteriolar diameter (139.1 ± 33.8 vs 165.1 ± 29.1; adjusted P = .007) and wider retinal venular diameter (237.9 ± 42.2 vs 214.9 ± 44.8; adjusted P = .045). Significant and independent associations were demonstrated for retinal arteriolar narrowing and E/A ratio (adjusted β = 0.744, P = .031) and for retinal arteriolar diameter and E/e’ ratio (adjusted β = −0.158, P = .001) after controlling for age, gender, body mass index, ambulatory systolic blood pressure, low‐density lipoprotein cholesterol, and retinal venular diameter. In untreated MH subjects, retinal arteriolar diameter, a marker of microvascular damage, was independently associated with echocardiographic markers of diastolic dysfunction. These findings might underscore the hypothesis that microvascular disease could contribute to cardiac remodeling.     

Is it possible to predict the onset of nocturnal asymptomatic hypoglycemia in patients with type 1 diabetes receiving insulin degludec? Potential role of previous day and next morning glucose values

Aims/IntroductionTo determine whether the occurrence of nocturnal asymptomatic, serious, clinically important hypoglycemia (NSH) could be predicted based on glucose values on the previous day and the following morning of the day of onset.Materials and MethodsThis study examined patients with type 1 diabetes who underwent continuous glucose monitoring assessments and received insulin degludec. NSH was defined as glucose level <54 mg/dL detected between 24.00 and 06.00 hours. The participants were evaluated to determine the following: (i) glucose level at bedtime (24.00 hours) on the previous day (BG); (ii) fasting glucose level (FG); and (iii) the range of post‐breakfast glucose elevation. The patients were divided into those with NSH and those without, and compared using t‐tests. Optimal cut‐off values for relevant parameters for predicting NSH were determined using receiver operating characteristic analysis.ResultsThe study included a total of 31 patients with type 1 diabetes (mean glycated hemoglobin value 7.8 ± 0.7%). NSH occurred in eight patients (26%). BG and FG were significantly lower in those with NSH than in those without (P = 0.044, P < 0.001). The range of post‐breakfast glucose elevation was significantly greater in those with NSH than in those without. The cut‐off glucose values for predicting NSH were as follows: BG = 90 mg/dL (sensitivity 0.83/specificity 0.75/area under the curve 0.79, P = 0.017) and FG = 69 mg/dL (0.83/0.75/0.86, P = 0.003).ConclusionsThe results showed that in patients with type 1 diabetes receiving insulin degludec, BG <90 mg/dL and FG <69 mg/dL had an approximately 80% probability of predicting the occurrence of NSH.     

Digital thermal monitoring techniques to assess vascular reactivity following finger and brachial occlusions

Digital thermal monitoring (DTM) is an alternative, noninvasive, methodology to evaluate endothelial function using temperature change on finger as a surrogate measure of the magnitude of vascular reactivity index (VRI). A most recent modification to the technique includes the application of occlusion cuff at the base of a finger. We evaluated the validity of DTM compared with the standard flow‐mediated dilation (FMD) protocol. Thirty‐eight (22 males; 38 ± 15 years) participants were studied. Occlusion cuff was placed over the right antecubital fossa or at the base of the right index finger. Temperature monitors were placed on bilateral index fingers to assess change in temperature throughout 5‐min occlusion and recovery phases. VRI values obtained with the finger occlusion (1.58 ± 0.29 AU) were not significantly different from VRI measured with the brachial artery occlusion (1.55 ± 0.26 AU; p = .47), and the agreement of VRI values was confirmed in the Bland‐Altman plot with a mean difference of −0.03 ± 0.34 (95% confidence interval: −0.15 to 0.09). Shear rate_AUCI was significantly correlated with VRI obtained from brachial occlusion (r = .34) and finger occlusion VRI (r = .54; all p < .05). Moreover, brachial FMD was significantly correlated with brachial occlusion VRI (r = .69; p < .05) and finger occlusion VRI (r = .53; p < .05). Therefore, finger‐based VRI may be a valid and novel alternative measure of endothelial function that is more suitable than the standard FMD or hyperemic shear rate for the assessment of endothelial function in the routine clinical setting.     

Polysomnography‐derived sleep parameters as a determinant of nocturnal blood pressure profile in patients with obstructive sleep apnea

Obstructive sleep apnea causes blood pressure (BP) surges during sleep, which may lead to increased sleep‐onset cardiovascular events. The authors recently developed an oxygen‐triggered nocturnal BP monitoring system that initiates BP measurements when oxygen desaturation (SpO₂) falls below a variable threshold. The association between nocturnal BP parameters obtained by nocturnal BP monitoring and simultaneously examined polysomnography‐derived sleep parameters in 116 patients with obstructive sleep apnea (mean age 57.9 years, 85.3% men) was studied. In multivariable analysis with independent factors of age, body mass index, sex, and polysomnography‐derived measures (apnea‐hypopnea index, apnea index, arousal index, lowest SpO₂, and SpO₂ < 90%), apnea‐hypopnea index (β = .26, P = .02) and lowest SpO₂ (β = −.34, P < .001) were independent determinants of hypoxia‐peak systolic BP (SBP), defined as the maximum SBP value measured by nocturnal BP monitoring. Similarly, apnea‐hypopnea index (β = .21, P = .04) and lowest SpO₂ (β = −.49, P < .001) were independent determinants of nocturnal SBP surge, defined as the difference between the hypoxia‐peak SBP and the average of the SBP values within 30 minutes before and after the hypoxia‐peak SBP, measured by the fixed‐interval function in the manner of conventional ambulatory BP monitoring. In conclusion, in polysomnography‐derived parameters, lowest SpO₂, defined as the minimum SpO₂ value during sleep, is the strongest independent determinant of hypoxia‐peak SBP and nocturnal SBP surge measured by nocturnal BP monitoring. Our findings suggest that the severity of the decrease in SpO₂ and the frequency of such decreases would be important indicators to identify high‐risk patients who are likely to develop cardiovascular events specifically during sleep.     

Pulse wave velocity progression over a medium‐term follow‐up in hypertensives: Focus on uric acid

The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow‐up period in hypertensive patients. Specific sex analysis was done due to the well‐known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow‐up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow‐up, despite better BP values (−8.5 ± 24.6 for SBP and −7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P < 0.001) with mean ΔPWV of+ 0.5 ± 2.2 m/s. A total of 61 patients were hyperuricemic (14.4%), and they present higher PWV baseline (9.0 ± 2.5 vs 8.5 ± 1.8 m/s, P = 0.03) without significant differences in ΔPWV. Hyperuricemic female (6.2%, 11 patients) presents higher baseline PWV without significant differences in ΔPWV. No differences were found in arterial stiffness in hyperuricemic males (20.4%, 50 patients). UA showed association with baseline and ΔPWV in the whole population but it loses statistical significance at the linear regression model. Same figures were also for sex analysis. Our findings provide evidence that baseline UA levels are not determinants of PWV progression over a median follow‐up of 3.8 years’ in hypertensive patients.     

Stage I hypertension is associated with impaired systolic function by strain imaging compared with prehypertension: A report from the prever study

High blood pressure (BP) is associated with higher rates of cardiovascular events, even in stage I hypertension (HTN) and prehypertension (preHTN). Lower left ventricular (LV) systolic function, assessed by global longitudinal strain (GLS), has been demonstrated in individuals with HTN compared to individuals with normal BP, but a comparison of individuals with preHTN and stage I HTN was not described to date. The PREVER study includes two randomized double‐blind controlled trials, performed in volunteers with preHTN (PREVER‐prevention trial) or stage I HTN (PREVER‐treatment trial), aged 30‐70 years. A subsample of patients of both trials had GLS measured from 2D echocardiograms performed at baseline and after 18 months of follow‐up. We compared baseline data from both studies and, among stage I HTN patients, clinical and echocardiographic correlates of GLS were determined. Participants with preHTN (n = 91;53% female; 55 ± 9 yo) and stage I HTN (n = 105; 44% female; 55 ± 8 yo) had similar clinical parameters beyond the expected differences in BP levels. Participants with stage I HTN had lower GLS (−17.5 ± 2.5% vs −18.2 ± 2.4%, P = .03) compared with those with preHTN. In stage I HTN, lower GLS was associated with lower e'' and lower LV ejection fraction. In conclusion, patients in Stage I HTN may already express changes in GLS compared with individuals with preHTN, suggesting that even mildly difference in BP can be impact in subclinical systolic function.     

Pulse wave velocity is decreased with obesity in an elderly Chinese population

Obesity is generally considered an undesirable risk factor for cardiovascular disease; however, obese subjects with heart failure paradoxically can have better outcomes than their lean counterparts. This study aimed to investigate this characteristic in an elderly Chinese population. Elderly participants (N = 414, age 77 ± 11 years, 211 males) were recruited from a Chinese community‐dwelling elderly population. Subjects were divided into 3 groups according to body mass index (BMI ≤ 25, normal; 25‐28, overweight; and ≥28, obese). Arterial stiffness was assessed by brachial‐ankle pulse wave velocity (baPWV), and the atherosclerosis status was evaluated with the ankle brachial index (ABI). Brachial systolic blood pressure (BSBP) was significantly higher as BMI increased (135 ± 18.4, 138 ± 18.3, 147 ± 17.6 mm Hg; P = .003) adjusted for age, sex, and heart rate. However, baPWV was significantly lower as BMI increased (baPWV 1830 ± 18, 1793 ± 25, 1704 ± 36 cm/s; P = .008) in the three groups, even with additional adjustment for BSBP. BMI showed a significant negative correlation with baPWV (r = −.170, P = .001) after adjusting for confounding factors. Using multiple linear regression, BMI was negatively and independently associated with baPWV (β = −.190, P < .001) especially for age <80 years. Arterial stiffness, as measured by baPWV, is lower in overweight subjects in a Chinese elderly population compared to those with normal body weight. ABI showed no relationship with BMI. These findings suggest that reduced arterial stiffness in the overweight population, independent of confounding factors, may contribute to the explanation of the “obesity paradox.”     

Phase III,randomized, double-blind,placebo-controlled study to evaluate the efficacy and safety of teneligliptin monotherapy in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise

Aims/IntroductionAlthough the efficacy of teneligliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, has been amply studied for the treatment of type 2 diabetes, no clinical trials of teneligliptin have been carried out in China. We evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.Materials and MethodsThis multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study, carried out at 42 sites, enrolled type 2 diabetes patients with glycosylated hemoglobin 7.0 to <10.0% and fasting blood glucose <270 mg/dL. Patients were randomly assigned, in a 1:1 ratio, to treatment with 20 mg teneligliptin or a placebo (n = 127, each) administered orally once daily before breakfast for 24 weeks. Change in glycosylated hemoglobin from baseline to week 24 was the primary efficacy end‐point. Safety was assessed by the incidence of adverse events and adverse drug reactions.ResultsThe least square mean (LSM) change in glycosylated hemoglobin from baseline to week 24 was −0.95% with teneligliptin versus −0.14% with a placebo, yielding an LSM difference (teneligliptin vs placebo) of −0.80% (P < 0.0001). For the secondary end‐point, from baseline to week 24, the LSM change in fasting blood glucose was −21.9 mg/dL with teneligliptin versus −1.4 mg/dL with a placebo, yielding an LSM difference (teneligliptin vs placebo) of −20.5 mg/dL (P < 0.0001). The adverse event and adverse drug reaction incidence rates, including hypoglycemia, were similar in both groups.ConclusionsAt 24 weeks, teneligliptin was generally well tolerated and effective in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.