bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
EFFECTS OF DAPAGLIFLOZIN IN HIGH AND LOW DIETARY SALT INTAKE PATIENTS WITH ALBUMINURIC DIABETIC KIDNEY DISEASE: A SUBANALYSIS OF THE Y-AIDA STUDY
Authors: Kinguchi Sho , Wakui Hiromichi , Misumi Toshihiro , Azushima Kengo , Yamanaka Takeharu , Terauchi Yasuo , Tamura Kouichi
Published: April 2021

Objective:

Current guidelines recommend the intensive control of BP as well as blood glucose to reduce albuminuria and prevent the development of diabetic kidney disease (DKD). We reported that improved home BP profile with dapagliflozin is independently associated with amelioration of albuminuria in Japanese patients with DKD (Kinguchi, et al. Cardiovasc Diabetol. 2019). The aim of this subanalysis was to investigate the differences in home BP lowering effects between high and low dietary salt intake patients with albuminuric DKD.

Design and method:

The Yokohama Add-on Inhibitory efficacy of Dapagliflozin on Albuminuria in Japanese patients with type 2 diabetes (Y-AIDA) study was a prospective, multicenter, single-arm study. A total of 86 T2DM (HbA1c 7.0–10.0%) individuals with albuminuric DKD (UACR > = 30 mg/gCr, eGFR > = 45 ml/min/1.73m2) were enrolled, and 85 participants were administered with add-on dapagliflozin for 24 weeks. Subgroup analysis, in which patients were classified into 2 groups according to their urinary sodium excretion at baseline, was conducted to determine the change from baseline in home BP profile at week 24.

Results:

At baseline, office systolic BP and morning, evening, and nocturnal home systolic BP were comparable between high urinary sodium excretion group (high group) and low urinary sodium excretion group (low group) (144.0 ± 19.7 vs 140.4 ± 18.4, P = 0.4044; 138.5 ± 12.1 vs 136.4 ± 16.6, P = 0.5179; 137.4 ± 17.6 vs 134.4 ± 17.3, P = 0.4481; 124.7 ± 14.8 vs 125.9 ± 14.9, P = 0.7267). The change in evening home systolic BP was greater in high group than in low group (-13.1 ± 12.0 vs -6.4 ± 11.4, P = 0.0203). The change in office BP, and morning and nocturnal home BP were comparable between high group and low group.

Conclusions:

In albuminuric DKD patients who have high dietary salt intake, add-on dapagliflozin treatment resulted in a greater decrease in evening home BP than in those who have low dietary salt intake.
PREDIABETES, PREHYPERTENSION AND RISK FOR ALL-CAUSE AND CARDIOVASCULAR MORTALITY AMONG US ADULTS: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEYS
Authors: Chen Chao-Lei , Liu Lin , Huang Jia -Yi , Yu Yu-Ling , Shen Geng , Lo Kenneth , Huang Yu -Qing , Feng Ying -Qing
Published: April 2021

Objective:

Recent studies have suggested that prehypertension and prediabetes are associated with an increased risk for all-cause or cardiovascular mortality but the findings are inconsistent. The purpose of this study was to explore the associations of prehypertension alone, prediabetes alone, and prehypertension combined with prediabetes with risk for all-cause mortality and cardiovascular mortality among healthy US adults.

Design and method:

Data for this study were obtained from the 1999–2014 National Health and Nutrition Examination Surveys (NHANES), a representative survey of the civilian, non-institutionalized US population conducted by the Center for Disease Control and Prevention (CDC). A total of 23622 participants without baseline hypertension, diabetes and cardiovascular disease (CVD) were enrolled after applying the inclusion and exclusion criteria. Prehypertension was defined as systolic/diastolic blood pressure: 120–139/80–89mmHg. Prediabetes was defined as fasting glucose 100–125 mg/dL or a hemoglobin A1c (HbA1c) between 5.7% and 6.4%. Participants were followed for cardiovascular and all-cause mortality through 31 December 2015. Cox proportional hazards models, sensitivity analyses and Kaplan-Meier survival curves were performed.

Results:

Overall, 12272 (51.95%) of subjects at baseline did not have prehypertension and prediabetes, 5841 (24.73%) had prehypertension alone, 2757 (11.67%) had prediabetes alone, and 2752 (11.65%) had both prehypertension and prediabetes. During a median follow-up of 8.58 years, a total of 1039 (4.40%) all-cause deaths and 98 (0.41%) CVD-related deaths occurred. Compared with participants without either prediabetes or prehypertension, the multivariable adjusted hazard ratios for all-cause mortality among participants with prehypertension alone, prediabetes alone, and both prediabetes and prehypertension were 1.01 (95% CI 0.79, 1.3), 1.13 (0.83, 1.53), and 1.17 (0.89, 1.55) (P for trend= 0.199), as well as for cardiovascular mortality were 1.40 (95%CI 0.59, 3.32), 1.31 (0.45, 3.83), and 1.61 (0.64, 4.05) (P for trend= 0.365), respectively. Subgroup analyses by age, gender, race, BMI, smoke status, TG and HDL-C showed no significant interaction.

Conclusions:

Our findings suggested that neither prehypertension nor prediabetes, as well as prehypertension with concomitant prediabetes, was associated with an increased risk for all-cause and cardiovascular mortality.
THE EFFECT OF DAPAGLIFLOZIN ON 24-HOUR BLOOD PRESSURE AND ARTERIAL STIFFNESS IN PATIENTS WITH TYPE-2 DIABETES MELLITUS: A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL
Authors: Papadopoulou Eirini , Loutradis Charalampos , Tzatzagou Glyceria , Kotsa Kalliopi , Zografou Ioanna , Minopoulou Ioanna , Theodorakopoulou Marieta , Tsapas Apostolos , Karagiannis Asterios , Sarafidis Pantelis
Published: April 2021

Objective:

Arterial hypertension is present in > 90% of patients and arterial stiffness is a prominent risk factor for heart failure and overall mortality in patients with type-2 diabetes mellitus (DM). Previous evidence suggests that sodium-glucose transporter 2 (SGLT-2) inhibitors can effectively manage hyperglycemia, but also reduce office blood pressure (BP) levels and the incidence of heart failure and death in these patients. The aim of this study is to evaluate the effects of dapagliflozin on ambulatory blood pressure (BP) levels and arterial stiffness parameters in patients with type-2 DM.

Design and method:

This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 DM on monotherapy or combination therapy with two of: metformin, sulphonylurea, DDP-4 inhibitor, or insulin. Patients were randomized in a 1:1 ratio to oral dapagliflozin 10 mg per day or placebo for 12 weeks. Study participants underwent 24-h ambulatory BP monitoring with the Mobil-O-Graph NG monitor at baseline and study-end.

Results:

Baseline demographic, clinical and laboratory parameters were similar in the two groups (age 61.74 ± 6.73 vs 60.64 ± 9.35; p = 0.534). During follow-up, 24-hour brachial SBP decreased in the active (128.97 ± 12.57 vs 123.17 ± 12.35; p < 0.001) but was similar in the control group (128.95 ± 12.41 vs 128.86 ± 13.45; p = 0.942). 24-hour central SBP/DBP significantly decreased only in the dapagliflozin (117.41 ± 10.52/78.88 ± 7.25 vs 113.30 ± 8.75/77.25 ± 6.54; p = 0.002/p = 0.047) group. Corresponding reductions of 24-hour central SBP (-4.12 ± 8.00 vs -0.65 ± 7.77; p = 0.046) were greater with dapagliflozin than placebo. Aortic pulse pressure (PP) decreased only in the dapagliflozin group (38.53 ± 7.44 vs 36.05 ± 6.59 mmHg; p = 0.004). 24-hour heart-rate adjusted augmentation-index significantly decreased with dapagliflozin. Importantly, there was a significant difference in the change of 24-hour PWV (-0.16 ± 0.32 vs 0.02 ± 0.27; p = 0.007) favoring dapagliflozin.

Conclusions:

Treatment with dapagliflozin produce statistically significant and clinically meaningful reductions in 24-hour brachial and central BP levels and reduce PWV levels in type-2 diabetics. Improvement in these parameters may substantially contribute to the cardiovascular benefits of SGLT-2 inhibitors.
PREVALENCE OF CHRONIC HYPERTENSION IN PREGNANT WOMEN FOLLOWING THE 2017 ACC/AHA GUIDELINE CHANGE IN DIAGNOSTIC CRITERIA FOR HYPERTENSION
Authors: Reynolds Kristi , Zhou Hui , Bider-Canfield Zoe , Cheetham T. Craig , Portugal Cecilia , Bello Natalie A.
Published: April 2021

Objective:

To examine the effect of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline for high blood pressure (BP) on the prevalence of chronic hypertension in pregnant women.

Design and method:

We conducted a cross-sectional study among women aged 15–49 years who had a live or stillbirth between 2009 and 2014 within an integrated US healthcare system. We compared the prevalence of chronic hypertension by the 2017 ACC/AHA guideline (defined as BP > = 130/80 mmHg) and the American College of Obstetricians and Gynecologists (ACOG) guideline (defined as BP > = 140/90 mmHg) overall and stratified by maternal age at delivery and race/ethnicity. Chronic hypertension was defined as > = 2 high BPs from outpatient encounters on different days within 30 days and taken < = 20 weeks gestation. The lowest BP value was used when there were multiple measurements from a single encounter. Women dispensed antihypertensive medication and who had a diagnosis of hypertension were classified as having hypertension by both guidelines regardless of BP value.

Results:

A total of 143,191 unique pregnancies were included (mean age was 30.1 years; 51% Hispanic, 26% non-Hispanic White, 8% non-Hispanic Black, 13% Asian). The prevalence of hypertension by ACOG and AHA/ACC was 2.3% and 9.7%, respectively. Using the 2017 ACC/AHA guideline, we identified 108,512 (75.8%) women with normal BP (<120/80 mmHg), 20,808 (14.5%) women with elevated BP (120–129/< 80 mmHg), 12,658 (8.8%) with hypertension stage 1 (130–139/80–89 mmHg), and 1,213 (0.9%) with hypertension stage 2 (> = 140/90 mmHg). Using ACOG criteria, 139,937 (97.7%) women had BP < 140/90 mmHg (31,425 of these women (22.5%) had BP 120–139/80–89 mmHg) and 3,254 (2.3%) women had hypertension (27 of these women (0.8%) had severe hypertension defined as BP> = 160/110 mmHg). Younger women and non-Hispanic whites and Hispanics experienced larger increases in the prevalence of hypertension by the 2017 ACC/AHA guideline (Figure).

Conclusions:

Adoption of the 2017 ACC/AHA guideline to define hypertension increased the prevalence of chronic hypertension in pregnancy over 300%. Further research is needed to examine whether this lower threshold for defining hypertension in pregnancy is associated with increased maternal and neonatal complications.
PARAMETERS OF CHANGING COAGULATION SYSTEM IN PREGNANT WOMEN WITH PREECLAMPSIA
Authors: Kurbanov Bakhodir
Published: April 2021

Objective:

The reasons for the development of preeclampsia are multifactorial, complex and not fully understood. However, according to modern concepts, the leading role belongs to endothelial damage, changes in platelet function, as well as immunological and genetic factors. Purpose of our study: to investigate changes of hemostasiological indicators in women with preeclampsia.

Design and method:

We conducted a study of the blood coagulation system in 68 pregnant women in the third trimester, of which 34 were pregnant with a physiological course of the gestational period (control group) and 38 pregnant women with preeclampsia (main group). The age of the women surveyed ranged from 20 to 42 years. The average age of women in the main group was 28.13 ± 0.83, and in the control group, 29.27 ± 0.70 years.

Results:

A significant decrease in the average platelet count in women with severe preeclampsia relative to healthy pregnant women in the third trimester of pregnancy (161.2 ± 9.6 × 109 / l and 193.5 ± 8.7 × 109 / l) (P < 0.05) When studying platelet aggregation activity, we found that platelet aggregation activity was significantly higher in the main group –112.7 ± 3.5 compared with the control group — 99.8 ± 3.3 (P < 0.05).

The concentration of fibrinogen, the main substrate of blood coagulation, was slightly higher in pregnant women with preeclampsia - 4.0 ± 0.2 g / l than in women with physiological pregnancy - 3.5 ± 0.17 g / l. In pregnant women with preeclampsia in the III trimester, a statistically significant shortening of ABP was established - 43.9 ± 0.9 seconds compared with the control - 51.2 ± 0.2 seconds (P < 0.001).

Conclusions:

Women with preeclampsia have signs of a subacute form of disseminated intravascular coagulation and signs of thrombocytopathy and consumption coagulopathy in combination with a decrease in blood anticoagulant and fibrinolytic potential.
ATTENUATION OF PLACENTAL LIPID DEPOSITION BY GLUTAMINE SUPPLEMENTATION IMPROVES FETAL OUTCOME IN INSULIN-RESISTANT PREGNANT RATS
Authors: Olaniyi Kehinde , Olatunji Lawrence
Published: April 2021

Objective:

Maternal metabolic adaptation is critical for placental and fetal development, growth and survival. However, evidence exists that indiscriminate consumption of fructose-enrich drink (FRD) during pregnancy disrupts maternal-fetal metabolic tolerance and/or glucose homeostasis with consequent adverse pregnancy outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic pathologies. Nevertheless, the effects of GLN on FRD-induced placental lipotoxicity during pregnancy are unknown. The present study was conducted to investigate the protective effects of GLN on pregnancy outcomes of female rats exposed to gestational FRD.

Design and method:

Pregnant Wistar rats weighing 160–180 g were randomly allotted into control, GLN, FRD and FRD+GLU groups (6 rats per group). The groups received vehicle (p.o.), glutamine (1 g/kg), fructose (10%; w/v) and fructose plus glutamine respectively throughout the period of gestation. Insulin resistance (IR) and insulin sensitivity were estimated by homeostatic model of assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) respectively. Plasma and tissue biochemical analysis were determined using enzyme-linked immunosorbent assay kits or fluorescence assay as appropriate.

Results:

Data showed that FRD increased placental weight and decreased fetal length and weight. It also caused maternal insulin resistance with correspondent increase in blood glucose, plasma insulin and decreased insulin sensitivity. In addition, FRD increased placental triglyceride, total cholesterol, low density lipoprotein-cholesterol, free fatty acid, atherogenic lipid, lipid peroxidation (malondialdehyde), lactate and uric acid synthesis, and decreased nitric oxide, adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense.

Conclusions:

The present study demonstrates that high FRD consumption during pregnancy causes placental lipotoxicity-driven defects with consequent fetal growth restriction. The findings also suggest that glutamine supplementation improves fetal outcome by ameliorating placental defects through suppression of uric acid synthesis and lipid peroxidation, as well as enhancement of NO-dependent endothelial function and antioxidant defense (Figure 1). Similarly, the study also suggests that glutamine supplementation in pregnancy could be useful as a reprogramming intervention to prevent impaired placental-fetal development and subsequent newborn and adulthood metabolic-related syndromes (Figure 1).
MISMATCH BETWEEN AVAILABLE CAPACITY AND ESTIMATED NUMBER OF PHYSICIAN VISITS NEEDED FOR HYPERTENSION CARE: AN ANALYSIS OF WORLDWIDE DATA
Authors: Neupane Dinesh , Gao Yumin , Feng Yijing , Matsushita Kunihiro , Appel Lawrence J.
Published: April 2021

Objective:

In most countries, only physicians are allowed to prescribe antihypertensive medication. Thus physician capacity (number of clinic visits physicians can allocate for hypertension care) is a key determinant of hypertension control. The objective of this study is to estimate the gap in clinic visits between available visit capacity and number of visits needed for hypertension care worldwide.

Design and method:

Data from the Global Health Observatory of World Health Organization and the World Bank were used to calculate the total number of hypertensive patients in each country. We assumed that the average physician would have 5,000 clinic visits/year and patients with hypertension require at least three visits a year. The gap in clinic visits between available capacity and patient need was calculated for each country. The analysis was further stratified based on income group according to the World Bank classification.

Results:

We estimated that 67 countries do not have the capacity to provide at least three visits to each hypertensive patient (countries in light to dark orange/red in Figure). Most of those countries are in Sub-Sharan Africa (63%), East Asia and Pacific (16%) and South Asia (9%), and all are in lower middle income or low-income countries. Of these countries, 38 countries cannot provide even a single visit to a hypertensive patient. On the other hand, 98% of high-income countries and 77% of upper-middle-income countries have the capacity to provide at least three visits per patient per year. The largest gap is seen in India followed by Indonesia, Ethiopia and Bangladesh.

Conclusions:

There is a huge gap in clinic visits between available capacity and the estimated need for hypertension care in low and middle income countries. To fill this gap, countries will need additional physicians or more likely implement a system of task sharing with allied health workers, such as nurses and community health workers.
THE ASSOCIATIONS BETWEEN HYPERTENSION AND STROKE FROM MAY MEASUREMENT MONTH AND BETWEEN NATIONAL HYPERTENSION PARAMETERS WITH STROKE MORTALITY FROM THE GLOBAL BURDEN OF DISEASE
Authors: Lin Queran , Ye Tingxi , Beaney Thomas , Poulter Neil R.
Published: April 2021

Objective:

To characterise the association between stroke history and hypertension from the 2017 and 2018 May Measurement Month (MMM) blood pressure (BP) screening campaigns.

To identify whether national-level MMM hypertension parameters are associated with national stroke mortality statistics.

Design and method:

Three BP readings and self-reported demographic, lifestyle and cardiovascular risk factors were collected from 2,515,578 participants in 95 countries. National stroke mortality statistics and Socio-Demographic Index (SDI) were extracted from the Global Burden of Disease (GBD) study 2017. Hypertension was defined as a raised BP (systolic BP > = 140 mmHg or diastolic BP > = 90 mmHg based on the mean of the second and third readings), or on antihypertensive medication.

Multiple imputation using chained equations was performed to estimate mean BP readings where missing. Logistic and linear regression were applied, respectively, to the association between hypertension and stroke and between national-level GBD stroke mortality with MMM proportions with raised, treated and uncontrolled BP.

Results:

Low-middle-SDI countries in MMM had the highest age-sex standardised proportion of participants with a previous stroke (4.9%), compared with high-middle-SDI countries (1.4%). Globally, individuals with a history of stroke had a significantly higher mean BP than those without (6.6/1.7 mmHg higher, p < 0.001). Amongst post-stroke participants, antihypertensive medication appeared to mitigate the impact of lifestyle factors on the odds of hypertension.

Stroke mortality increased, on average, by 34 per 100,000 per 1% increase in the proportion of untreated individuals with raised BP (p = 0.006) and by 22 per 100,000 per 1% increase in proportion with treated but uncontrolled BP (p = 0.003). Stroke mortality decreased, on average, by 14 per 100,000 per 1% increase in the proportion of hypertensives treated (p = 0.01).

Conclusions:

Our study found suboptimal BP control among participants with a previous stroke globally, especially in low SDI countries. There was a significant association between national stroke mortality from GBD and the proportions of participants with raised or uncontrolled BP and of hypertensives treated in MMM. This suggests that despite lacking a population-based design, estimates from MMM broadly reflect rates of downstream mortality and that opportunistic screening can be an effective means of screening for hypertension.
FEASIBILITY AND ACCEPTABILITY OF A NOVEL INTEGRATION OF ABSOLUTE CARDIOVASCULAR DISEASE RISK ASSESSMENT INTO ROUTINE BLOOD CHOLESTEROL TESTING
Authors: Chapman Niamh , Fonseca Ricardo , Murfett Leigh , Beazley Kevin , Mcwhirter Rebekah , Schultz Martin , Nelson Mark , Sharman James
Published: April 2021

Objective:

Absolute cardiovascular disease (CVD) risk assessment is recommended for primary prevention of CVD, yet uptake in general practice is limited. Lipid profile requests at pathology services provides an opportunity to improve uptake by integrating absolute CVD risk assessment with this service. This study aimed to assess the feasibility of such an additional service.

Design and method:

299 participants (aged 45–74 years) referred to pathology services for blood cholesterol had variables required to determine absolute CVD risk measured (blood pressure, age, sex, smoking and diabetes status). Data were recorded via self-report on a computer-based application with minimal direction from staff. The absolute risk score was communicated via the report sent to the referring medical practitioner as per usual practice. Evaluation questionnaires were completed immediately post visit and at 1-, 3- and 6-month follow-up via telephone (n = 262).

Results:

Absolute CVD risk reports were issued for 90% of participants. Most participants (95%) reported that the length of time for the pathology service assessment was acceptable, and 91% that the self-directed computer-based application was easy to use. 78% reported a preference for pathology services to conduct absolute CVD risk assessment. Only 2% preferred a medical practitioner. Of follow-up participants, 202 (75%) had a consultation with a medical practitioner, during which, aspects of CVD risk prevention were discussed (cholesterol and blood pressure 74% and 69% of the time, respectively).

Conclusions:

Measurement of absolute CVD risk in pathology services is feasible, highly acceptable among middle to older adults and may increase uptake of guideline-directed care in general practice.
STUDY ON REDUCTION OF MICROALBUMINURIA AMONGST HYPERTENSIVE PATIENTS WITH USE OF TRIPLE COMBINATION THERAPY (TRIPLIXAM)
Authors: Arun Abhishek
Published: April 2021

Objective:

Persistent microalbuminuria is earliest indicator of Chronic Kidney Disease amongst hypertensive patients and is also associated with target organ damage resulting in stroke, retinopathy and adverse cardiovascular outcomes.

The present study was aimed to evaluate the reduction in microalbuminuria amongst uncontrolled essential hypertensive patients with use of triple combination therapy.

Design and method:

It was a hospital based cross sectional prospective study done on 50 essential hypertension patients having uncontrolled blood pressure and presence of microalbuminuria in urine. Total duration of therapy was 3 months and triple combination therapy used in study as antihypertensive was Triplixam (Perindopril 4 mg, Amlodipine 5 mg and Indapamide 1.25 mg). Patients having Diabetes and other co morbidities were excluded from the study. Patients were evaluated at baseline and end of study visit for SBP,DBP, Urine for albumin excretion. Ethical clearance was taken prior to inclusion of patients.

Results:

There was significant reduction in both SBP (18 mm Hg) and DBP (10 mm Hg) with use of triple combination therapy (Triplixam). Microalbuminuria turned to normal albumin excretion in urine that was statistically significant (p < 0.01) was most significant and convincing finding.

Conclusions:

Triplixam is an excellent triple agent that can reduce blood pressure promptly and bring about reduction in urine albumin excretion thereby decreasing risk of end target organ damage. Early detection of renal dysfunction through microalbuminuria and prompt treatment can confer future protection from end stage renal disease.
METABOLIC EFFECT OF A MINERALOCORTICOID RECEPTOR ANTAGONIST IN A NEW MODEL OF DIABETIC NEPHROPATHY
Authors: Palacios Roberto , Bonnard Benjamin , Lima-Posada Ixchel , Genty Marie , Jaisser Frederic
Published: April 2021

Objective:

Diabetic nephropathy (DN) is the most prevalent form of chronic kidney disease (CKD) and is associated with cardiovascular diseases. Several studies reported beneficial effects of mineralocorticoid receptor (MR) antagonists in DN, indicating the importance of aldosterone/MR axis in this pathology

We investigated the metabolic alterations associated to a new model of DN and explored the effect of the MR antagonist canrenoate and conditional MR knock-down

Design and method:

One month after CKD induction by 5/6 nephrectomy, mice were split in 4 groups: SHAM, CKD, CKD with 60% fat diet (CKD-HFD) and CKD-HFD treated with 30 mg/kg/day canrenoate (CKD-HFD-CAN). Another series was split in 2 groups CKD-HFD Ctrl and CKD-HFD-AdipoMRKO (in which the MR gene is deleted in adipocytes only). Glycated hemoglobin (HbA1c) was measured and glucose tolerance test (ipGTT) and insulin tolerance test (ipITT) were performed between 5 and 7 weeks after the starting of the diet/treatment. The whole body fat content was determined by MRI (Brucker). The comparisons were performed by one-way ANOVA and two-way ANOVA for the insulin and glucose tolerance tests. Results were considered significant with p < 0.05.

Results:

The body weight, the fat content, the epididymal visceral adipose tissue (EVAT) size and HbAc1 were significantly higher in the CKD-HFD group vs SHAM or CKD, an effect prevented by the treatment with canrenoate. The glucose tolerance and the response to insulin were impaired in CKD-HFD vs SHAM or CKD, an effect ameliorated by canrenoate (Table). The impact on body weight, fat content and EVAT size was similar in CKD-HFD-adipoMRKO mice when compared to CKD-HFD Ctrl mice, however the improvement of the glucose tolerance was milder (Table).

Conclusions:

MR antagonism improves metabolic alterations associated to DN, partially due to its effect on adipose tissue, which could be translated in a better prognosis of the disease
HYPERTENSION AND RENIN-ANGIOTENSIN SYSTEM BLOCKERS ARE NOT ASSOCIATED WITH EXPRESSION OF ANGIOTENSIN CONVERTING ENZYME 2 (ACE2) IN THE KIDNEY
Authors: Jiang Xiao , Eales James , Scannali David , Nazgiewicz Alicja , Prestes Priscilla , Maier Michelle , Denniff Matthew , Xu Xiaoguang , Saluja Sushant , Wystrychowski Wojciech , Zywiec Joanna , Zukowska-Szczechowska Ewa , Burrell Louise M. , Greenstein Adam , Bogdanski Pawel , Keavney Bernard , Morris Adrew P. , Heagerty Anthony , Samani Nilesh J. , Guzik Tomasz J. , Charchar Fadi J. , Tomaszewski Maciej
Published: April 2021

Objective:

Angiotensin converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) – the cause of COVID-19 disease. However, the effect of RAS-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported.

Design and method:

We examined how hypertension, its major metabolic co-phenotypes and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterised by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model.

Results:

Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis.

Conclusions:

Our results indicate that neither hypertension nor antihypertensive treatment are likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.