bluuebunny/crossref_metadata_2025_split huggingface dataset:
SELF-TESTING OF BLOOD PRESSURE ACCORDING TO THE DEPISTHTA® PROTOCOL IN THE POPULATION OF THE FRENCH LEAGUE AGAINST HYPERTENSION SURVEY 2019
Authors: Girerd X. , Pathak A. , Vaïsse B. , Hanon O. 
Published: April 2021

ABSTRACT

Objective: The FLAHS 2019 survey was organized to determine the distribution of blood pressure in the adult population over 35 years of age through the use of self-screening.

Design and method: FLAHS surveys are conducted by a self-administered questionnaire sent by mail to individuals from the Kantar Health Metascope permanent sampling frame (panel representing the population living in metropolitan France). Among the positive respondents to the question: Do you have a device to measure blood pressure at home? It was obtained measurements according to the depistHTA® protocol (3 consecutive measurements leaving an interval of 1 minute between each measurement while keeping the sitting position, without getting up between each measurement). The average of the last 2 measurements was taken to define the subject's BP.

Results: Of the 7627 subjects aged 35 and over, 1706 had a blood pressure monitor. Self-testing was possible in 50% of subjects taking antihypertensive treatments (938 subjects) and 15% of untreated patients (767 subjects).
Among the untreated: 18.8% had BP > = 140 or 90; 29.1% had BP > = 135 or 85 and 64.9% had BP > = 120 or 80. Among subjects taking antihypertensive drugs: 64.1% had BP < 140 and 90; 50.4% had BP < 135 and 85 and 14.6% had BP < 120 and 80.
Among untreated people aged 35 to 54 years: 16.1% had BP > = 140 or 90; 25.7% had BP > = 135 or 85 and 59.2% had BP > = 120 or 80.
Among those treated with antihypertensive drugs and aged 35 to 54 years: 68.5% had BP < 140 and 90; 54.8% had BP < 135 and 85 and 25.0% had BP < 120 and 80.

Conclusions: Self-screening for blood pressure is possible in the general population. When the depistHTA® protocol is used, BP > = 140 or 90 is observed in 18.8% of untreated subjects aged 35 and over, or 5 million subjects in metropolitan France. In treated hypertensive patients, BP < 135 and 85 is noted in 50.4% of patients, indicating that control of treated hypertension is not improving in France.
depistHTA® is available on stores.
RENIN-ANGIOTENSIN SYSTEM INHIBITION, CARDIORESPIRATORY FITNESS AND MORTALITY RISK IN DIABETIC PATIENTS
Authors: Pittaras Andreas , Grassos Haralampos , Doumas Michael , Myers Jonathan , Faselis Charles , Kokkinos Peter 
Published: April 2021

Objective:
Patients with type 2 diabetes mellitus (T2DM) have significantly higher risk of cardiovascular events and mortality. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) decrease mortality risk in T2DM patients. Cardiorespiratory fitness (CRF) is associated with lower mortality risk in T2DM patients. However, the combined effects of CRF and ACEI/ARBs on mortality risk in T2DM patients has not been assessed.

Design and method:
We identified 6,888 T2DM patients (age 58.3 + 10.1 years) with no evidence of ischemia as indicated by a maximal standardized exercise treadmill test. We established two CRF categories based on age-adjusted median peak metabolic equivalents (METs) achieved: Unfit (5.4 ± 1.3 METs; n = 3,474) and Fit (9.0 ± 2.3 METs; n = 3414). We then formed 2 groups within each CRF category (treated and not treated with ACEI/ARBs) for a total of four CRF-ACEI/ARBs groups. Cox proportional hazards models, adjusted for known risk factors were constructed to assess the CRF-ACEI/ARBs interaction and mortality risk association.

Results:
During a follow-up of 14.2 + 6.9 years, 2,495 patients died, accounting for 25.5 events/ 1,000 person-years of observation. Patients treated with ACE/ARBs had 25% lower mortality risk compared to those not treated with ACE/ARBs (HR 0.75; 95% CI: 0.69-0.82). When CRF-ACEI/ARBs categories were considered, Unfit individuals not treated with ACEI/ARBs had 24% higher mortality risk compared to those treated with ACEI/ARBs (HR 1.24; 95% CI 1.11–1.38). For Fit individuals, the risk was 26% lower (HR: 0.74; CI: 0.66–0.83) for those not treated with ACEI/ARBs and 45% lower in those treated with ACEI/ARBs (HR 0.55; 95% CI 0.48–0.62).

Conclusions:
ACEI/ARBs therapy and increased CRF are effective in lowering mortality risk in in T2DM patients. The combination of ACEI/ARBs and higher CRF was synergistic, resulting in substantially lower mortality risk than either therapy alone.
CYB5R3 BIASES SOLUBLE GUANYLYL CYCLASE ACTIVATION IN RESISTANCE ARTERIES
Authors: Durgin Brittany , Hahn Scott , Straub Adam 
Published: April 2021

Objective:
Nitric oxide (NO) regulates blood pressure by binding the reduced heme iron on soluble guanylyl cyclase (sGC) in vascular smooth muscle cells (SMC) which leads to the production of cyclic guanosine 3’,5’-monophosphate (cGMP) and vasodilation. In cardiovascular disease, oxidative stress causes oxidation or loss (apo-) of the sGC heme, impairing NO binding and causing vasoconstriction. Subsequently, new therapeutic compounds termed sGC activators have been developed for use in cardiovascular disease to target oxidized heme, and to a greater extent apo-sGC, to cause irreversible, NO-independent reactivation of cGMP production and vasodilation. However, few studies have defined the impact of NO-independent sGC activation on vascular physiology in non-stressed conditions.

Design and method:
To address this, we performed vasoreactivity studies on resistance and aortic arteries under non-stressed, physiological conditions and telemetry for in vivo blood pressure recordings.

Results:
Interestingly, we found that resistance arteries are log-orders more sensitive to sGC activator BAY 58–2667 than conduit aortic arteries in non-stressed conditions. This suggests that resistance arteries may contain a previously unknown, physiologically activatable pool of heme oxidized and/or apo-sGC that can be activated independent of NO and disease. We have previously published that cytochrome b5 reductase 3 (CYB5R3) reduces the oxidized heme sGC to its NO-sensitive, reduced state which confers resilience from systemic hypertension. We hypothesized that CYB5R3 may serve as a rheostat in physiological blood pressure and sGC activator function. In transgenic CYB5R3 overexpression (CYB5R3 OE) mice, we found that resistance arteries, but not aorta have a blunted response to sGC activator induced vasodilation and blood pressure lowering in unstressed conditions (n = 4–8/group). OE CYB5R3 mice also exhibit a ∼7 mmHg decreases in pulse pressure and impaired blood pressure reduction in response to an acute injection of BAY 58–2667 when compared to controls (n = 5/group). Consistent with this, no difference in vasodilation response to NO donor sodium nitroprusside (SNP) was observed between CYB5R3 OE and littermate controls irrespective of vessel type (n = 2–6/group).

Conclusions:
These data suggest that CYB5R3 is important in regulating resistance artery sensitivity to sGC activator BAY 58–2667 likely via governing sGC redox state in non-stressed, physiological conditions.
STRUCTURAL ALTERATIONS OF MICROCIRCULATION IN CANCER PATIENTS TREATED WITH ANTIANGIOGENIC DRUGS
Authors: Brami Valeria , Coschignano Maria Antonietta , De Ciuceis Carolina , Rossini Claudia , Berruti Alfredo , Rosei Claudia Agabiti , Paini Anna , Cosentini Deborah , Volta Alberto Dalla , Salvetti Massimo , Porteri Enzo , Petelca Alina , Nardin Matteo , Chiarini Giulia , Muiesan Maria Lorenza , Rizzoni Damiano 
Published: April 2021

Objective:
Development of hypertension as well as alterations in microcirculation (decreased capillary density) have been recently reported to be associated with tyrosine kinase inhibitor (TKI) treatment in cancer patients (Dalbeni A, et al. Cancers 2019). An increased blood pressure has also been demonstrated with direct anti-VEGF inhibitor. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect also the structure of retinal arterioles which seems to have prognostic significance in term of cardiovascular events.

Design and method:
For this purpose, we included 14 patients with a diagnosis of cancer (renal n = 8, lung n = 2, gastrointestinal n = 2, thyroid n = 1, breast n = 1) underwent a treatment neither with a TKI (n = 11: sunitimib n = 5, pazopanib n = 4, nintedanib n = 1, lenvatinib n = 1) or with an anti-VEGF antibody (n = 3: bevacizumab n = 2, ramucirumab n = 1). All patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total (after venous congestion) capillary density were assessed by capillaroscopy whereas retinal arteriole morphology was obtained by Adaptive Optic. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after three (T3) and six (T6) months after treatment. Changes in antihypertensive treatment was also assessed.

Results:
Result are reported in the Table. Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or added additional agents) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters. Basal capillary density resulted reduced by antiangiogenic drugs after three or six months.

Conclusions:
Our preliminary data suggest that an increase of antihypertensive treatment is necessary in patients treated with a tyrosine kinase inhibitor (TKI) or a direct VEGF inhibitor, confirming a pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular alterations seem to be partially preserved since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.
RELATIONSHIPS BETWEEN CHOROIDAL THICKNESS AND 24 H PULSE PRESSURE IN HYPERTENSIVE PATIENTS
Authors: Mulè Giuseppe , Vadala Maria , Guarrasi Giulia , Sorce Alessandra , Montalbano Katia , Carollo Caterina , Mancia Ettore , Cottone Santina 
Published: April 2021

Objective:
The choroid is a pure vascular structure and its thinning may reflect a microvascular damage, that may be the local expression of a more generalised vascular injury. Choroid may be easily damaged directly by acute and chronic severe elevation of blood pressure (BP). However, all the studies exploring the association of BP values with choroidal thickness yielded conflicting results. Our study was aimed to assess in hypertensive patients the relationships between choroidal thickness and “office” and 24-hour BP readings.

Design and method:
We enrolled 158 consecutive hypertensive subjects (age: 48 ± 13 years) attending our Hypertension Centre. All the patients underwent clinic BP measurements, 24-h ambulatory BP monitoring (ABPM) and morphological evaluation of the retino-choroidal district by SS-OCT. OCT measurements were performed according to the ETDRS protocol whose map divides the macula into 9 subfields. The circular grid is centred over the fovea and consists of 3 concentric rings,the inner and outer rings are further divided into quadrants: temporal, nasal, superior, and inferior. The retinal and choroidal thicknesses were automatically calculated by the OCT mapping software and only one eye of each subject was randomly selected for analysis and for sake of brevity we show only the data referring to the mean choroidal thickness. (MCT).

Results:
MCT (250 ± 62 m) showed significant correlations with: mean 24-h DBP (r = 0.18; p = 0.02) and diurnal (r = 0.21; p = 0.009), mean 24-h pulse pressure (PP) (r = - 0.30; p < 0.001), of the day (r = - 0.19; p = 0.02) and of the night (r = - 0.25; p = 0.002). The correlation between the 24-hour PP and the SCM remains significant even after accounting for confounders in the multiple linear regression (r = - 0.18; p = 0.02).

Conclusions:
Our results, highlighting an inverse association between choroid thickness and 24-hour PP (possible index of arterial stiffness) seem to reinforce the hypothesis that choroidal thinning may be the expression of systemic vascular damage.
HYPERCOG COGNITIVE SCREENING IN OLDER ADULTS WITH HYPERTENSION: A PILOT STUDY
Authors: D’Andria Maria Flora , Rivasi Giulia , Turrin Giada , Tortu’ Virginia , Falzone Daniele , Giuliani Evelina , Giordano Antonella , Ungar Andrea 
Published: April 2021

Objective:
Hypertension is a risk factor for cognitive impairment. According to the 2018 ESH/ESC guidelines for hypertension management, cognitive screening tests should be included in the assessment of older hypertensive adults. Numerous screening tests are available, but their diagnostic accuracy in hypertensive people has been scarcely investigated. The present study aimed at analyzing and comparing the diagnostic accuracy of the MiniCog, the Montreal Cognitive Assessment (MoCA), the Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT) in older hypertensive patients.

Design and method:
The study was carried out in the Referral Centre for Hypertension in Elderly of Careggi Hospital, Florence, Italy, between February 2017 and May 2019. Subjects aged 65 or older without a prior diagnosis of cognitive impairment were enrolled. Participants underwent a cognitive screening using the MMSE, the MoCa, the Mini-Cog and the CDT, followed by a complete neuropsychological evaluation. Depressive symptoms and functional status were assessed with the Geriatric Depression Scale and the Basic and Instrumental Activities of Daily Life, respectively. Sensitivity and specificity were assessed for each tests and their combinations, using the ROC curves for the MMSE and the MoCA.

Results:
Among 94 participants undergoing a complete cognitive evaluation, 35 (37.2%) had mild cognitive impairment or dementia. Seven patients (7.44%) had a multi-domain cognitive impairment. According to the ROC curves, the best detection of cognitive impairment could be achieved with a cut-off score of 24 for the MoCA (AUC 0.746) and 27.5 for the MMSE (AUC 0.689). The MoCA had the highest diagnostic accuracy, providing a sensitivity of 80% and a specificity of 59%. A cognitive screening including both the Mini-Cog and the MMSE provided a higher sensitivity (74%) and specificity (51%) than the MMSE alone (sensitivity and specificity of 69% and 52%, respectively).

Conclusions:
In conclusion, we observed a high prevalence of cognitive impairment (37.2%) among older hypertensive outpatients with no prior diagnosis of dementia. The MoCA with a cut-off of 24 seems to have a good diagnostic accuracy in this population and could be included in the assessment of hypertension-related organ damage, to screen for cognitive impairment.
POPULATION ATTRIBUTABLE FRACTION OF HYPERTENSION FOR ONSET OF ISCHEMIC STROKE AMONG ATRIAL FIBRILLATION PATIENTS WITH AND WITHOUT ANTICOAGULATION
Authors: Maeda Toshiki , Nishi Takumi , Funakoshi Shunsuke , Tada Kazuhiro , Tsuji Masayoshi , Satoh Atsushi , Kawazoe Miki , Yoshimura Chikara , Arima Hisatomi 
Published: April 2021

Objective:
CHA2DS2-Vasc score is the most widely used risk score for prediction of ischemic stroke among patients with atrial fibrillation (AF). Although hypertension, a component of the CHA2DS2-Vasc score, is an established risk factor of ischemic stroke, there is still uncertainty surrounding the magnitude of its effects in the total patient population with AF, particularly according to use of oral anticoagulants. The objective of the present analysis was to investigate the effects and population attributable fractions (PAF) of hypertension for incidence of ischemic stroke among AF patients with/without anticoagulation in a real-world setting of Japan.

Design and method:
We conducted an observational study of 21,581 patients with AF using health-check and insurance claim data in Japan from 2005 to 2017. Hypertension was defined as blood pressure levels higher than 140/90 mm Hg or use of blood pressure lowering medications. Outcome was fatal and non-fatal ischemic stroke. We employed COX proportional hazard model to obtain hazard ratios (HR) and in order to assess the PAF of hypertension and other risk factors for incidence of ischemic stroke.

Results:
A total of 11,848 AF patients (54.9%) were on oral anticoagulants. During a mean 2.8-year follow-up period, 343 ischemic stroke events occurred. Hypertension was a significant risk factor for incident ischemic stroke among AF patients without anticoagulation (adjusted HR 2.62 [95%CI 1.72 to 4.01] p < 0.001) and among those on anticoagulants (adjusted HR 1.50 [1.08 to 2.09] p = 0.017). The largest PAF was also observed for hypertension among components of the CHA2DS2-Vasc score (47.2% [33.3% to 58.1%] for patients without anticoagulation and 23.1% [6.1% to 37.0%] for those on anticoagulants).

Conclusions:
In this large-scale, real-world study of Japanese patients with AF, hypertension was the most prominent risk factor among components of the CHA2DS2-Vasc score, even though they were on oral anticoagulants. In order to obtain maximum reduction in incidence of ischemic stroke among patients with AF, effective management and prevention of hypertension would be most essential irrespective of use of oral anticoagulants.
PREDIABETES AND RISKS FOR ALL-CAUSE AND CARDIOVASCULAR MORTALITY BY HYPERTENSION STATUS: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEYS
Authors: Liu Lin , Huang Yuqing , Huang Jiayi , Chen Chaolei , Yu Yuling , Shen Geng , Lo Kenneth , Feng Yingqing 
Published: April 2021

Objective:
Current recommendation suggests prediabetes testing for adults with overweight or obesity who have at least one cardiovascular risk factor. Given the detrimental effects of combined prediabetes and hypertension on CVD events, it is important to understand whether testing should be conducted for adults with hypertension regardless of other cardiovascular risk factors

Design and method:
Participants from the 1999–2014 National Health and Nutrition Examination Surveys (NHANES) aged over 18 years without diabetes were enrolled for analysis. Participants were classified according to their status of prediabetes and hypertension, and followed up for cardiovascular and all-cause mortality till 31 December 2015. Cox proportional hazards models were built to estimate the hazard ratios (HR) for all-cause and cardiovascular mortality among participants with prediabetes, hypertension, and both. Results were also stratified by age, gender and demographic backgrounds to explore subgroup differences in associations.

Results:
A total of 34,047 participants with median follow-up period of 8.4 years were included in analysis. Prediabetes was defined as fasting plasma glucose between 100 and 125 mg/dL, or hemoglobin A1c between 5.7 and 6.4%, or self-reported hypoglycemic drug use. Hypertension was defined as systolic/diastolic blood pressure over 140/90 mmHg and/or self-reported antihypertensive medication use. At baseline, 5011 (14.7%) of them had combined prediabetes and hypertension. When compared with participants without prediabetes nor hypertension, prediabetes alone was not associated with all-cause (HR [95% CI]: 1.12 [0.93, 1.34]) nor with cardiovascular mortality (1.30 [0.74, 2.29]); hypertension alone was significantly associated with all-cause (HR [95% CI)]: 1.30 [1.11, 1.52]) and cardiovascular mortality (1.97 [1.22, 3.16]); combined prediabetes and hypertension was significantly associated with all-cause mortality (HR [95% CI]): 1.40 [1.19, 1.65]) and cardiovascular mortality (2.40 [1.49, 3.85]).According to subgroup analysis, participants with combined prediabetes and hypertension had a higher risk of all-cause mortality among those aged < 60 (HR: 2.19), White population (HR: 1.41) and male participants (HR:1.52).

Conclusions:
Prediabetes might elevate the risks of all-cause and cardiovascular mortality among people with hypertension.
ARTERIAL STIFFNESS IMPROVEMENT IN HYPERTENSIVE TYPE 2 DIABETIC PATIENTS: DISSIMILAR EFFECTS OF CANAGLIFLOZIN AND PERINDOPRIL
Authors: Ramirez Agustin Jose , Sanchez Maria Josefina , Sanchez Ramiro Ariel 
Published: April 2021

Objective:
We have shown in hypertensive type 2 diabetic patients (DM) a strong correlation between serum uric acid (SUA) and pulse wave velocity (PWV). Additionally, after 6 months treatment, we found a significant PWV improvement either with perindopril or canagliflozin that, when adjusted for office BP values, the PWV improvement was blunted in the perindopril treated patients while in those receiving canagliflozin a significant effect still remains. Thus, the aim of the present work was to evaluate in normoglycemic diabetic hypertensive patients with normal renal function, the effects and relationships of canagliflozin and perindopril on SUA, 24hs AMBP and carotid femoral PWV.

Design and method:
For 6 month, 40 hypertensive DM patients, under metformin 2000 mg and amlodipine, received canagliflozin 100–300 mg 10 mg daily (n = 20, 10 females, 59 ± 4y) while other 20 patients (8 females, 62 ± 4y) received perindopril 10 mg on top. Laboratory parameters determined at baseline and after a 6-month treatment were: HbA1C, fasting blood glucose level, glomerular filtration rate, SUA, urine acid uric, 24 h ambulatory blood pressure monitoring (ABPM) and PWV.

Results:
After 6 months treatment with canagliflozin, a decrease in PWV, (12.29 ± 0.16 to 8.49 ± 0.09m/sec; p < 0.001), HbA1C (8.1 to 7.0%; p < 0.05), SUA (7.87 ± 0.06 to 6.83 ± 0.06 mg/%; p < 0.05), and 24 h ABPM (154 ± 6/96 ± 5 to 141 ± 3/86 ± 4mmHg; p < 0.01) was observed. Similarly, after Perindopril, a decrease in 24hs ABPM (152 ± 7/98 ± 7 to 139 ± 6/84 ± 5mmHg; p < 0.05), PWV (12.53 ± 0.15 to 8.92 ± 0.19m/sec; p < 0.001) and SUA (7.77 ± 0.18 to 7.35 ± 0.11mg%; p < 0.05) was observed. Nevertheless, the SUA reduction induced by canagliflozin (-13.20 ± 0.71%) was greater (p < 0.001) than the induced by Perindopril (-4.98 ± 1.30%).
A significant correlation between delta SUA and delta PWV was only observed with canagliflozin (r: 0.82, p < 0.001). Urine uric acid increased from 350 ± 20 to 580 ± 30 mg/24hs (p < 0.05) with canagliflozin, whereas no changes were observed with perindopril.

Conclusions:
In patients with type 2 DM and hypertension, both canagliflozin and perindopril were able to ameliorate blood pressure and arterial stiffness values. Moreover, canagliflozin improved PWV associated to uric acid reduction. It is suggested that the reduction in SUA and the increase in UA urine excretion seems to have an intrinsic vascular wall effect therefore, it may reduce cardiovascular risk.