bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARISON OF EFFECTS OF BLOOD PRESSURE, BLOOD GLUCOSE AND LIPID VARIABILITY ON CARDIOVASCULAR PROGNOSIS IN DIABETIC PATIENTS
Authors: Joo Hyung Joon , Chung Se Hwa , Kim Yong Hyun , Kim Eung Ju
Published: June 2023

Objective:

Metabolic abnormalities such as dyslipidemia, glucose and high blood pressure are common in diabetic patients. Variabilities in these measures have been reported as a potential residual cardiovascular risk factors. This study aimed to analyze the relationship between variabilities of blood pressure, blood glucose, total cholesterol and triglyceride levels (metabolic variability parameters) and their effects on cardiovascular prognosis in diabetic patients.

Design and method:

A total of 22,310 diabetic patients aged 40 years or older who had their blood pressure, blood glucose, total cholesterol, and triglyceride levels measured three or more times for three years after January 1, 2017 at three tertiary general hospitals were selected. They were divided into high/low groups based on their systolic blood pressure (SBP), blood glucose, total cholesterol (TC) and triglyceride coefficient of variation (CV) over a 3-year period. The incidence of major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke, was compared between groups, and significant risk factors for MACE were estimated by multivariable Cox regression analysis.

Results:

The number of measurements for 3 years was 15.1 times for SBP, 7.8 times for TC, 6.9 times for triglyceride, and 8.6 times for glucose. The correlation between the CV of SBP and the CV of glucose was highest, and the correlation between the CV of SBP and the CV of triglycerides was the lowest. All groups with high CV had a higher incidence of MACE than those with low CV (2.5% vs 6.0% for SBP CV groups, 3.0% vs 5.5% for TC CV groups, 3.8% vs 4.7% for triglyceride CV groups, 2.7% vs 5.8% for glucose CV groups). Multivariable Cox regression analysis suggested male, creatinine, prior myocardial infarction, SCORE2, SBP CV, TC CV, mean TC, and mean triglyceride as independent risk predictors for MACE in diabetic patients (HR 1.087 (95% CI 1.068 – 1.107) for SBP CV, 1.023 (1.016 – 1.031) for TC CV).

Conclusions:

Metabolic variability parameters, especially SBP CV and TC CV are important residual risk factors for cardiovascular events in diabetic patients.
WHITE COAT EFFECT DURING BLOOD PRESSURE SELF SCREENING: PREVALENCE AND DETERMINANTS IN THE FRENCH HYPERTENSION OBSERVATORY
Authors: Girerd Xavier , Buyer Paul De , Boualit Robert , Pathak Atul , Asmar Roland , Lopez-Sublet Marilucy
Published: June 2023

Objective:

To evaluate the frequency and determinants of the white coat effect in subjects performing a standardized self monitoring of blood pressure.

Design and method:

The French Hypertension Observatory is a non profit initiative set up by the Hypertension French Research Fundation to evaluate the cardiovascular risk of employees working in companies in France. During ‘prevention days’ organized in the company's premises between 9:00 a.m. and 5:00 p.m., volunteer employees performed a self-test of their blood pressure using a validated automatic blood pressure monitor with arm cuff. Self unattended BP measurements were performed with 3 measures 1 minute apart. 4012 subjects were included. The difference between SBP 1 and 3 measurements were considered to define the white coat effect (WCE).

Results:

The prevalences of WCE (for at least 10 or 20 mmHg of WCE) when first measure indicates 140 for SBP are detailed in the table.

Conclusions:

The white coat effect is also observed in subjects who measure their blood pressure unattended. During a blood pressure self-screening testing, subjects aged less than 35 years, those with a BMI < 20 or female participants more frequently present a white coat effect than other subjects.
IMPACT OF SEASONAL BLOOD PRESSURE CHANGES ON VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY
Authors: Dell’Oro Raffaella , Schumacher Helmut , Böhm Michael , Grassi Guido , Koon Teo K. , Mahfoud Felix , Parati Gianfranco , Redon Josep , Yusuf Salim , Mancia Giuseppe
Published: June 2023

Objective:

Visit-to-visit blood pressure (BP) variability (V) associates with an increased risk of cardiovascular events. Limited information is available, however, on the factors responsible for this phenomenon. We investigated the role of seasonal BP modifications on the magnitude of BPV and its impact on cardiovascular risk.

Design and method:

In 28365 patients included in the ONTARGET and TRANSCEND trials the on-treatment systolic (S) BP values were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for each BPV quintile (Q), quantified by the coefficient of variation (CV) of between-visits mean SBP. The differences in the risk of morbid and fatal cardiovascular events between Qs were assessed by the Cox regression model.

Results:

SBP was 4 mmHg lower in summer than in winter regardless of sex, age, diabetes, baseline SBP and achieved SBP of the patients. Winter/summer SBP differences contributed significantly to each SBP-CV and the contribution increased progressively from Q1 to 5. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio of the primary endpoint of the trials, i.e.morbid and fatal cardiovascular events (Q5 vs Q1: 1.51, 95% CI 1.36 - 1.67). A similar trend was observed for secondary endpoints. This was also the case after subtraction of the SBP seasonality.

Conclusions:

Winter/summer SBP differences significantly contribute to visit-to-visit SBP variability and more so as variability becomes greater. This contribution, however, does not explain the adverse prognostic significance of visit-to-visit BP variations.
ASSOCIATION BETWEEN NOCTURNAL VARIATION IN BLOOD PRESSURE AND RISK OF ACUTE ISCHEMIC STROKE: A SYSTEMATIC REVIEW
Authors: Ztriva Eleftheria , Daios Stylianos , Kachtsidis Vasileios , Dimas Grigorios , Toumpouras Theodoros , Andronoglou Markos , Kakaletsis Nikolaos , Kanellos Ilias , Polychronopoulos Georgios , Kaiafa Georgia , Tegos Thomas , Savopoulos Christos
Published: June 2023

Objective:

Blood pressure (BP) is a dynamic parameter characterized by fluctuations during the 24-hour period. Variability of BP has been associated with cardiovascular risk and the occurrence of acute ischemic stroke (AIS). Circadian variation in BP during the night shows some basic patterns. The purpose of this study is to to correlate deviations from baseline patterns of circadian BP variation with the risk of AIS to select the optimal therapeutic intervention.

Design and method:

To complete our study, we systematically reviewed the literature from 1990-2022 through electronic medical databases (MEDLINE, Scopus and Cochrane).

Results:

During the nighttime hours, BP drops 10 - 20% in normotensive and untreated hypertensive patients - a dipping phenomenon, followed by a rapid and gradual increase during waking hours. In the studies being reviewed, patients were classified according to the rate of fall in systolic BP during 24-hour recording into four categories: the extreme-dippers drop >20%, dippers drop >10% and <20%, non-dippers drop <10% and >0%, and reverse-dippers or risers drop <0%. Deviating from standard dipping patterns is associated with an increased risk of AIS and highlights the value of chronotherapy, whereas no significant difference is observed in stroke prognosis. The extreme-dipping phenomenon is associated with the occurrence of ischemic stroke (IS), either due to under-treatment or due to subsequent morning hypertensive spike, whereas aggressive antihypertensive treatment seems to be significantly responsible. Interestingly, the occurrence of microbleeds in IS territory has been strongly associated with the reverse-dipping pattern.

Conclusions:

Overnight BP variation is an independent and robust predictor of cardiovascular risk, including AIS. Nocturnal BP may constitute a therapeutic target for the prevention of AIS. However, the available data on the effect of antihypertensive drugs and the implementation of chronotherapy with pre-sleep medication are conflicting in terms of improving cardiovascular risk. Therefore, at present, current guidelines for the treatment of BP do not recommend the aforementioned therapeutic approach as the best treatment in day-to-day clinical practice. More extensive and targeted studies are needed in the future to confirm the potential benefits of the application of chronotherapy in the prevention of AIS.
VARIATIONS IN THE PERCEPTION OF BITTER TASTE MAY MODULATE THE RISK OF HYPERTENSION
Authors: Oliveira Alda Pereira da Silva , Costa Marta , Santos Carolina , Ferreira Joana , Barbosa Paula , Mascarenhas Mário , Bicho Manuel
Published: June 2023

Objective:

The perception of bitter taste conditioned by the TAS2R38 gene (combined Proline/Alanine/Valine and Isoleucine phenotypes) may be associated with food consumption. Individuals with one copy of PAV are bitter tasters, with two copies of AVI are non-bitter tasters, and with AAV < AAI < PAI are intermediate bitter tasters. Consumption salt balance is determined by the function of the epithelial sodium channels that lead to its preference and the bitter taste receptors associated with its aversion. In turn, a chronic high salt intake was associated with the inhibition of bitter receptors with less salty taste aversion leading to potential higher consumption and risk of hypertension. The objective was to evaluate the influence of bitter taste perception on the risk of arterial hypertension.

Design and method:

DNA from 339 individuals was quantified and genotyped by reverse transcription followed by polymerase chain reaction (RT-PCR). Blood pressure was determined by standard methods. Arterial hypertension was diagnosed in 141 individuals who were compared with 198 normotensive individuals. Thyroid functional status is determined by clinical history, physical examination, FT4, FT3, TSH, antiperoxidase, antithyroglobulin, and TRAB antibodies. Hypothyroidism at 33.3%, hyperthyroidism 14.3% and euthyroidism 52.35%. Statistics: chi2 and t-Student, considering significance <0.05.

Results:

The frequencies of the TAS2R38 diplotypes were: PVI/PVI (26%); PVV/PVI (0.9%); PVV/AVI(10.6%); PVV/AVV(0.9%); AVV/AVV(2.4%); PAI/PVI(0.3%); PAV/PVI(5.95%); PAV/AVI(37.5%); AAV/AAV(12.7%); PAV/AAV(2.75%) and PAV/AAI(0.3%). The TAS2R38 AAV/AAV and PAV/AAV diplotypes showed a lower risk of hypertension adjusted for thyroid dysfunction, compared to the remaining diplotypes of this gene, with OR = 0.458[0.236-0.887], p = 0.021. Other diplotypes showed no significant association.

Conclusions:

Individuals with bitter tasting associated with AAV genotypes may be less likely to develop hypertension compared to other bitter tasters. The lower risk of hypertension in these genotypes may be associated with greater functionality of bitter taste receptors associated with aversion to salt intake. In conclusion, the genetic polymorphisms of the bitter taste gene may influence the risk for arterial hypertension and may therefore be considered potential future therapeutic targets. The absence of bitter-insensitive individuals (AVI/AVI) in this sample limits the understanding of the influence of these genotypes on the risk of hypertension.
OVERWEIGHT OR OBESITY DOES NOT CARRY AN INCREASED RISK OF ADVERSE OUTCOME IN YOUNG TO MIDDLE AGE PEOPLE WITHOUT METABOLIC ABNORMALITIES
Authors: Palatini Paolo , Saladini Francesca , Mos Lucio , Fania Claudio , Battista Francesca , Ermolao Andrea , Garavelli Guido , Rattazzi Marcello
Published: June 2023

Objective:

Overweight or obesity (OvOb) is a risk factor for the development of cardiometabolic complications. However, according to some investigators, OvOb developed without hypertension and insulin resistance may be considered as a benign phenotype. The aim of the present study was to investigate the prognostic significance of OvOb (BMI> = 25 kg/m2) without concomitant metabolic abnormalities in young-to-middle-age subjects screened for stage 1 hypertension.

Design and method:

We examined 1208, 18-to-45-year-old participants from the HARVEST study. Mean age was 33.1 ± 8.6 years and BP 145.5 ± 10.6/93.5 ± 5.7 mmHg. Participants were classified into four groups according to whether they had OvOb or not (0/1) and had normal (group 0) or at least one abnormal (group 1) metabolic syndrome parameter (glucose, triglyceride, HDL-cholesterol, and average 24-hour BP). The predictive role of OvOb/metabolic group for incident hypertension and cardiovascular or renal events (MACE) was evaluated in Cox survival analyses, adjusting for other risk factors and several confounders.

Results:

ObOv was present in 51.1% of the participants and at least one metabolic abnormality was present in 74.5%. Among the subjects with OvOb, 20.2% had no metabolic abnormalities, 40.5% had one metabolic abnormality, and 39.3% had two or more metabolic abnormalities. During a median follow-up of 17.4 years, 80.6% of the participants developed hypertension requiring pharmacological treatment and 8.9% had a MACE. In adjusted Cox models, OvOb participants with at least one metabolic abnormality had an increased risk of incident hypertension (HR, 1.43; 95%CI,1.12 - 1.81, p = 0.003) and MACE (2.34,1.03 - 5.36, p = 0.043) compared to those with normal metabolic parameters. Among the participants with normal BMI, a similar metabolic-related increase in risk was found for the hypertension outcome (HR, 1.52;95%CI,1.21 - 1.92, p = 0.0003), but not for MACE (1.64,0.70 - 3.81, p = 0.25). In a Cox model in the whole population, when controlled for each other the metabolic group (0/1) was a predictor of hypertension (p < 0.0001) and MACE (p = 0.028) whereas the ObOv group was not (p>0.05).

Conclusions:

These data show that in young-to-middle-age people, an abnormal metabolic profile is an important predictor of future hypertension needing treatment and MACE. OvOb without metabolic abnormalities does not carry an increased risk of adverse outcomes.
URIC ACID RELATIONSHIPS WITH LIPID PROFILE AND ADIPOSITY INDICES: IMPACT OF DIFFERENT HYPERURICEMIC TRESHOLDS
Authors: Maloberti Alessandro , Vanoli Jennifer , Finotto Alessandra , Bombelli Michele , Facchetti Rita , Redon Pau , Mancia Giuseppe , Grassi Guido
Published: June 2023

Objective:

Previous studies focused on the relationships between Serum Uric Acid (SUA) and lipids have found an association mainly with triglycerides. Furthermore, previous studies on adiposity indices have been focused on the evaluation of the Visceral Adiposity Index (VAI). The present study was aimed at providing within the same population a systematic evaluation of lipids and adiposity indices with SUA, employing both the classic cutoff for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study.

Design and method:

We analyzed data collected in 1892 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA, lipid profile and variables necessary to calculate VAI, Cardio-Metabolic Index (CMI) and Lipid Accumulation Product (LAP).

Results:

At linear regression model (corrected for confounders) SUA correlated with all the lipids values (with the strongest for triglycerides) and adiposity indices. When the two different cutoffs were compared, the URRAH one was significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non-HDL, P < 0.001) while this was not the case for the classic one. Regarding adiposity indices the classic cutoff displays highest OR as compared to the URRAH one.

Conclusions:

Newly reported URRAH cutoff for hyperuricemia better relate to atherogenic lipoprotein (LDL and non-HDL) when compared to the classic one. The opposite has been found for adiposity indexes where the classic cut-off seems to present highest performance. Among adiposity indexes, LAP present the highest OR for the relationship with hyperuricemia.
CHANGES IN AMBULATORY BLOOD PRESSURE DURING THE TRANSITION TO RETIREMENT
Authors: Karelius Saana , Vahtera Jussi , Suorsa Kristin , Heinonen Olli Juhani , Pentti Jaana , Niiranen Teemu Juhani , Stenholm Sari
Published: June 2023

Objective:

Retirement is a major life event characterized by removal of work-related stressors and changes in health behaviours. The association between retirement and changes in blood pressure (BP), and particularly in ambulatory BP, has been scarcely studied. We aimed to examine changes in ambulatory BP during retirement transition.

Design and method:

Two hundred and fifty ageing workers (mean age 63.2 years, 84% women) from the Finnish Retirement and Aging study participated in annual office BP measurements and 114 (mean age 63.1, 90% women) of them underwent annual ambulatory BP measurements before and after retirement. On average, the participants provided data on ambulatory BP at 2.7 (range 2 - 4) measurements. We used generalized linear models to examine BP changes at retirement. The FIREA study was conducted in accordance with the Helsinki declaration and was approved by the Ethics Committee of Hospital District of Southwest Finland (ETMK: 84/1801/2014). All participants gave written informed consent.

Results:

Most marked changes in BP during the follow-up were observed for asleep SBP, which decreased before retirement, increased during retirement transition and plateaued after retirement (before retirement vs. retirement transition P = 0.07 and after retirement vs. retirement transition P = 0.02). Awake SBP and 24-h SBP declined with most apparent decrease before retirement (before retirement vs. retirement transition P = 0.07 and P = 0.07). Awake DBP and 24-h DBP showed relatively consistent decline throughout the follow-up with no differences between the time periods. SBP and DBP dipping reduced before and during retirement transition, but not after retirement. Among shift workers, asleep BP increased and BP dipping decreased more than in regular day workers.

Conclusions:

Retirement was found to associate with beneficial changes in awake BP but unfavourable changes in asleep BP, especially in shift workers.
CUMULATIVE BLOOD PRESSURE LOAD AND INCIDENT DEMENTIA, COGNITIVE FUNCTION, AND ALL-CAUSE AND CARDIOVASCULAR DEATHS IN ADULTS AGED 70 YEARS AND OLDER
Authors: Xu Xiaoyue , Catts Vibeke , Harris Katie , Wang Nelson , Numbers Katya , Trollor Julian , Brodaty Henry , Rodger Anthony , Sachdev Perminder , Schutte Aletta
Published: June 2023

Objective:

Few studies have focused on the contribution of long-term exposure to elevated BP to dementia and deaths, particularly among older adults. We examined the prognostic value of cumulative BP (cBP) and cBP load in relation to incident dementia, cognitive decline, all-cause and cardiovascular deaths among adults aged 70 years and above, followed over 15 years. We also explored whether seated vs standing BP has more predictive value for these outcomes.

Design and method:

The Sydney Memory and Aging Study (N = 1,037) comprised a cohort of community-dwelling individuals aged 70 - 90 years without dementia, recruited from two areas of Sydney, Australia. Baseline data collection was performed in 2005-2007 and the cohort was followed every two years for 7 waves until 2021. Sitting and standing systolic, diastolic BP and pulse pressure (PP) were measured from wave 1 to 3. Cumulative sitting and standing BP and its load were calculated from the area under the curve. We assessed the association of BP parameters with incident dementia, cognitive function, all-cause and cardiovascular deaths between wave 4 and 7, in Cox proportional hazards models.

Results:

A total of 520 participants with three waves of BP data were included (47.7% men, median age at baseline, 77 [IQR: 74 - 81] years). In the multivariable-adjusted Cox model, cumulative pulse pressure (cPP) load was associated with a higher risk of dementia (sitting p for trend = 0.004; standing p for trend = 0.023), and lower global cognitive scores (sitting p for trend = 0.005; standing p for trend = 0.022). However, no significant associations were found upon additional age adjustment (p for tend>0.05). Sitting and standing cPP and cPP load were also associated with higher risk of all-cause deaths (all p for trend < 0.006). No associations were found for cumulative systolic or diastolic sitting or standing BP and dementia and cognition, as well as all-cause and cardiovascular deaths in both crude and adjusted models.

Conclusions:

Long-term cPP load predicted a significant age-dependent increase in risk for dementia, cognitive decline, and deaths in adults older than 70 years.
ONGOING ANTI-HYPERTENSIVE TREATMENT DOESN’T IMPACT ON OUTCOME ON MEDIUM-LONG TERM SEQUELAE OF PATIENTS WITH MODERATE TO SEVERE COVID-19 PNEUMONIA
Authors: Cattaneo Chiara , Salvotti Francesca , Leidi Francesca , Pellegrinelli Riccardo , Geroldi Veronica , Loro Giorgia , Reale Scilla , Vaccarello Paola , Cherubini Fabio , Borghi Erika , Napoli Federico , Malerba Paolo , Ciuceis Carolina De , Rosei Claudia Agabiti , Rizzoni Damiano , Boari Gianluca E.M.
Published: June 2023

Objective:

One “hot” topic that remains to be elucidated is the possible role of anti-hypertensive drugs on middle and long term outcome of COVID-19 pneumonia.

Namely, ACE2 receptor is highly expressed on the surface of cardiac and pulmonary cells, and it is used by coronaviruses, to enter host cells; specifically, the interaction between the “spike” protein of coronaviruses and ACE2 has been identified as a key factor for the virus transmission.

This makes the role of ACE-inhibitors and Angiotensin Receptor Blockers (ARBs) drugs extremely controversial and their role – if any – is still to be elucidated. Moreover, it is still unclear whether these drugs may have any impact on SARS-CoV-2 sequelae.

Design and method:

In this retrospective study, we analysed a group of 70 hypertensive unvaccinated patients treated in our Medicine ward for moderate to severe COVID-19 pneumonia during pandemic who survived and accepted to undergo a follow-up visit after a mean of 260 days including phone interview, standard laboratory tests, chest x-ray and/or chest computed tomography, spirometry with evaluation of DLCO. Patients were divided in three groups according to hypertensive treatment: ACE-inhibitors (n. 27) or ARBs (n. 21) or other anti-hypertensive medication.

The considered groups where homogeneous (see table)

Results:

As shown in the table, biochemical, radiological and respiratory data were not significantly different.

Again, we did not find any significant difference in terms of number of non-specific radiological alterations (i.e. ground-glass opacities, irregular linear/reticular opacities), lung fibrosis, spirometry data, DLCO diffusion, persisting effort dyspnoea.

Biochemical data were, once more, substantially super-imposable in the two groups

Conclusions:

In conclusion, in our study, we could not detect any difference in middle-long term outcome nor in complication type or number in the groups of hypertensive patients undergoing different treatments.

This result seems to support and to strengthen the idea that ACE-inhibitors and ARBs do not play a significant role on onset, evolution and middle-long term outcome of moderate to severe COVID-19 pneumoniae: although the number of follow-up patients is very small, we did not find any difference in sequelae in both groups.
COVID-19 AND ARTERIAL STIFFNESS IN VACCINATED YOUNG ADULTS WITHOUT PRIOR CO-MORBIDITIES. A CROSS-SECTIONAL ANALYSIS OF THE FIT@4COVID COHORT STUDY
Authors: Pereira Telmo , Lira Fábio , Caseiro Armando , Castanheira Joaquim , Coelho-e-Silva Manuel
Published: June 2023

Objective:

The long-term consequences of COVID-19 amongst survivors of acute infection are unknown, particularly on the cardiovascular system. Given the ability of the virus to affect the arterial wall, the question emerges to whether COVID-19 has a negative modulating effect of the vascular aging trajectory, conveying accelerated arterial stiffening and endothelial dysfunction, and thus, contributing to an increased CV risk over the life course.

Objective:

The main aim of this study was to ascertain the consequences of COVID-19 on arterial stiffness, by measuring PWV and thereby evaluating the presence of EVA. Secondary objectives of the study include investigating the effect of the SARS-CoV-2 infection on haemodynamic parameters measured by PWA.

Design and method:

A cross-sectional analysis of the initial data from the Fit@4COVID cohort was made. Carotid-femoral pulse wave velocity (PWV) and carotid pulse wave analysis (PWA) were evaluated in participants with (Covid19 group) and without (Control group) prior infection with SARS-CoV-2. Groups were matched for age and gender. Blood samples were taken for confirmation of prior exposition to the virus and to study the immune and inflammatory profile.

Results:

A total of 60 participants, equally divided in two groups, were enrolled, with a mean age of 20 ± 1.0 years. No significant differences were observed between groups concerning anthropometric, sociodemographic and clinical characteristics. Significant differences between-groups were observed for PWV (control: 5.84 ± 0.33 m/s, Covid19: 6.19 ± 0,47 m/s; p < 0.01), even after adjusting for mean arterial pressure (p = 0.019). Significant differences were also depicted for central systolic blood pressure, with 106.40 ± 9.27 mmHg in the control group and 115.00 ± 11.23 mmHg in the Covid19 group (p = .012). Similar results were found when observing brachial systolic blood pressure, central pulse pressure and brachial pulse pressure, all of which showed higher values in the Covid19 group.

Conclusions:

The cross-sectional analysis of the initial Fit@4COVID data buttresses a relevant impact of the SARS-CoV-2 virus over the arterial wall, even in healthy young adults with mild forms of COVID-19. The long-term effects of COVID-19 over the cardiovascular system remains to be demonstrated.
COVID-19 AND MORTALITY IN HYPERTENSIVE PATIENTS ACCORDING TO CARDIORESPIRATORY FITNESS
Authors: Faselis Charles , Doumas Michael , Pittaras Andreas , Samuel Immanuel Babu , Gorsuch Belinda , Ladas Alexandros , Lavie Carl , Myers Jonathan , Kokkinos Peter
Published: June 2023

Objective:

COVID-19 mortality risk increases with the presence of underlying comorbidities, including hypertension. Epidemiologic evidence also suggests an inverse association between self-reported physical activity and COVID-19 cases and deaths. However, no information exists regarding the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized exercise treadmill test (ETT) and mortality in hypertensive patients.

We assessed the hypothesis that CRF is inversely and independently associated with COVID-19 mortality risk in non-vaccinated hypertensive patients

Design and method:

From 2020 to 2021, we identified 17,358 hypertensive patients (mean age: 60.3 ± 8.2 years) with a normal response to an exercise tolerance test (ETT), prior to COVID-19. We established five CRF categories based on age-stratified quintiles of peak metabolic equivalents (MET) achieved: Least-Fit (4.7 ± 1.2 METs; n = 3,486); Low-Fit (7.1 ± 1.3; n = 4,616); Moderate-Fit (8.4 ± 1.3 METs; n = 3,320); Fit (10.3 ± 0.9 METs; n = 4,084); and High-Fit (12.8 ± 1.6 METs; n = 1,852). Multivariable Cox proportional hazard models were constructed to estimate hazard ratios (HR) and 95% confidence intervals [CI] for mortality across CRF categories. The models were adjusted for age, gender, race, comorbidities, medications, hospitalization, intubation, and time elapsed between ETT and COVID-19. The Least-Fit category was used as the reference group.

Results:

Results: During the follow-up of 100 days, 1,853 individuals died (10.7%). The risk for death was 7% lower for each 1-MET increase in exercise capacity (HR = 0.93, CI: 0.92-0.95; p < 0.001). The risk across fitness categories declined progressively with increased CRF and was 26% lower for the Least-Fit individuals (HR = 0.74; CI: 0.66 - 0.84), approximately 30% to 40% lower for Moderate-Fit and Fit, and 50% lower (HR = 0.50; CI: 0.41 - 0.62; p < 0.001) for High-Fit patients.

Conclusions:

Increased CRF was inversely related to COVID-19 mortality risk in hypertensive patients. The association was graded and independent of comorbidities.
IMPACT IN RENAL PARAMETERS OF ACHIEVED BP DURING ANTIHYPERTENSIVE TREATMENT IN DIABETIC SUBJECTS. REAL WORLD DATA
Authors: Martinez Fernando , Calderon Jose Miguel , Diaz Javier , Sauri Inma , Fernandez Antonio , Lidón Laura , Forner Maria Jose , Redon Josep
Published: June 2023

Objective:

The controversy to use an intensive or standard antihypertensive treatment in diabetic subjects is still not solved. The objective of the present study was to assess the impact of BP levels in renal parameters (progression of KDIGO stage and decrease of 20% GFR in two years) during treatment in Type 2 diabetic subjects.

Design and method:

T2DM patients were included. During the study, SBP, DBP, eGFR, UAE, HbA1, lipid levels were measured and average of values in each six months periods was calculated. Cox proportional hazard models time-derived was applied to assess the impact of BP levels in progression of one stage in KDIGO (stages I to IV) and a 20% reduction in the eGFR in 2 year-period. Covariates of age, sex, smoking, previous cardiovascular events, HbA1c, lipid levels and drug treatments for hypertension, diabetes, anticoagulant or antiaggregant were included in the analysis.

Results:

52553 patients (age 66+/-11 yr, gender 51.2% females) with eGFR and 47558 with UAE measured during the study were included. 3851, 74 per 104/patients/year decline eGFR and 3568, 67 per 104/patients/year progress at least one KDIGO level. Overall, the increment or reduction of risk for the achieved SBP and DBP adjusted for all the other variables, as well as the risk for each of the covariates are in the figure for progression of KDIGO. SBP below 120 mmHg increases the risk of both eGFR and KDIGO whatever the DBP. DBP <70 mmHg does not increase the risk unless SBP >150 mmHg.

Conclusions:

In diabetic patients’ intensive reduction of SBP <120mmHg but not DBP<70mmHg increases the risk of renal damage.
A SYSTEMATIC REVIEW AND META-ANALYSIS ABOUT THE PREVALENCE OF FUNCTIONING ADRENAL INCIDENTALOMAS
Authors: Sconfienza Elisa , Tetti Martina , Forestiero Vittorio , Veglio Franco , Mulatero Paolo , Monticone Silvia
Published: June 2023

Objective:

Adrenal hyperfunction is associated with an increased risk of cardio-metabolic complications in subjects with adrenal incidentaloma. The aim of our study was to assess the prevalence of autonomous/possible autonomous cortisol secretion, primary aldosteronism, pheochromocytoma and Cushing syndrome in patients with adrenal incidentaloma.

Design and method:

We performed a comprehensive search of multiple databases (PubMed, Ovid MEDLINE, Web of Science) for potentially relevant studies without language restriction, up to February 2022. Studies were excluded if the diagnostic criteria used for diagnosing the hormonal alteration were not available or not in agreement with the available guidelines; in case of duplicate reports or if the studies were performed on selected cohorts of patients/specific populations.

Results:

We included 36 studies in the final analysis. The overall prevalence of functioning adrenal incidentalomas was 27.5%. Autonomous cortisol secretion/possible autonomous cortisol secretion, with a prevalence of 11.7% (95% C.I. 8.6, 15.7), was the most frequent hormonal alteration, while primary aldosteronism occurred in 4.4% of the patients (95% C.I. 3.1, 6.2). Subgroup analysis showed that primary aldosteronism was more prevalent in patients from Asia compared with patients from Europe/America, on the contrary, autonomous cortisol secretion/possible autonomous cortisol secretion had a lower prevalence in Asian countries. At meta-regression analysis, the prevalence of autonomous cortisol secretion/possible autonomous cortisol secretion was influenced by the proportion of female patients, while the prevalence of primary aldosteronism was positively associated with the proportion of patients with hypertension and the publication year. Finally, pheochromocytoma and Cushing syndrome prevalence were 3.8% (95% C.I. 2.8, 5.0) and 3.1% (95% C.I. 2.3, 4.3), respectively.

Conclusions:

We confirmed a wide heterogeneity among studies, that was partially explained by the differences in the populations included, such as the female gender and the geographical regions where patients were recruited; moreover, the year of the study publication plays a potential role in the observed effect, thus underlying an increasing awareness of these hormonal alterations in the latest years.
CXCR4-DIRECTED [68GA]GA-PENTIXAFOR PET/CT AS A NOVEL DIAGNOSTIC MODALITY IN PRIMARY ALDOSTERONISM
Authors: Baz Amir Hossein Chaman , Gotthardt Martin , Deinum Jaap , Langenhuijsen Johan
Published: June 2023

Objective:

Primary aldosteronism (PA) is caused by autonomous production of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction (‘subtyping’) is crucial, PA is cured by adrenalectomy in unilateral PA and is treated by medication in bilateral PA. Subtyping is currently done by adrenal vein sampling (AVS). We propose a new diagnostic imaging modality employing the PET-tracer [68Ga] Ga-PentixaFor. This tracer reportedly has high uptake in APAs, whereas uptake is low in BAH or normal adrenals. The goal of this study is to determine concordance of [68Ga] Ga-PentixaFor PET/CT and AVS. Secondary outcomes are optimal timepoint for scanning and quantitative criteria for lateralization at the optimal timepoint.

Design and method:

This study is step 1 of a two-step randomized controlled diagnostic trial. We included patients with PA from Radboudumc Nijmegen and UMC Utrecht, confirmed by an intravenous salt-loading test. Patients underwent AVS and [68Ga]Ga-PentixaFor PET/CT. A dynamic scan was performed to determine optimal timepoint for scanning in the first 6 patients. The main outcome was the concordance of AVS and [68Ga]Ga-PentixaFor PET/CT. The SUVmax was used to determine lateralization in [68Ga]Ga-PentixaFor PET/CT.

Results:

Nineteen patients underwent adrenal vein sampling and a [68Ga]Ga-PentixaFor PET/CT. The optimal timepoint of scanning was 1h post injection. AVS showed lateralization in 13/19 patients. Using a cut-off of SUV¬max-ratio of 1.4, concordance was 68%. (figure 1) Using a Bayesian prediction model, the predicted concordance is: 67% (CI80% = 53 - 79).

Figure 1: Scatter dot plot of the SUVmax Ratio in patients who had lateralization or no lateralization on AVS with a cut-off value of 1.4.

Conclusions:

[68Ga]Ga-PentixaFor PET/CT is a new imaging modality with high concordance with AVS. It is safe, readily available and as an out-patient procedure has the potential to improve subtyping in PA. With these preliminary results we have sufficient evidence of concordance to proceed to step 2 of the two-step trial: A pragmatic randomized controlled diagnostic trial, in which patients will be randomized in either [68Ga]Ga-PentixaFor PET/CT or AVS.
SALT RESTRICTION COMBINED WITH RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM BLOCKADE IS A POTENT ANTIHYPERTENSIVE STRATEGY IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Schneider Holger , Sarkis Anna -Lina , Sturm Lisa , Britz Vera , Lechner Andreas , Potzel Anne L , Müller Lisa Marie , Heinrich Daniel A , Künzel Heike , Nowotny Hanna F , Seiter Thomas Marchant , Kunz Sonja , Bidlingmaier Martin , Reincke Martin , Adolf Christian
Published: June 2023

Objective:

The relationship between high dietary salt intake and high blood pressure is well established. Recommendations for salt restriction have found their way into major guidelines for essential hypertension. Patients with primary aldosteronism (PA), the most common endocrine cause of arterial hypertension, are believed to be exquisitely salt sensitive, i.e., respond particularly well to salt restriction. However, surprisingly little efforts have been made to determine the precise impact of salt restriction in patients with PA.

We, therefore, set out to implement a moderate salt restriction in patients with PA to assess its impact on blood pressure and secondary health outcomes.

Design and method:

We used nutritional education and continuous self-monitoring via a smartphone app to reduce salt intake in 41 patients with PA for a time span of 12 weeks. All patients were on mineralocorticoid receptor antagonist therapy and had stable blood pressure. Patients were monitored every 4 weeks with blood pressure and urine sampling and detailed blood work at weeks 0 and 12. Mental well-being was addressed by validated scoring systems.

Results:

Patients achieved a significant reduction of dietary salt intake (from 9.1 to 5.2 g/d) and of blood pressure (from 130/84 to 121/81 mmHg). We also registered a significant loss of body weight (-1.4 kg). While subjects initially featured PHQD scores compatible with depression, scores normalized at the end of the study. Multivariate regression analysis revealed that cumulative intake of drugs targeting the renin-angiotensin-aldosterone system was an independent predictor of blood pressure reduction.

Conclusions:

Salt restriction is an effective treatment in patients with PA. Patient empowerment by education and self-monitoring promotes salt restriction. Effects are facilitated by concomitant RAAS blockade. Salt restriction, despite being moderate, also improves mental well-being.
GENETIC DELETION OF AT1A RECEPTORS SELECTIVELY IN THE RENOMEDULLARY INTERSTITIAL CELLS OF THE KIDNEY MEDULLA ATTENUATES ANGIOTENSIN II-INDUCED HYPERTENSION
Authors: Li Xiao , Hassan Romana , Zhuo Jia
Published: June 2023

Objective:

The present study tested the hypothesis that genetic deletion of angiotensin II (Ang II) AT1 (AT1a) receptors selectively in the renomemdullary interstitial cells (RMICs) of the kidney medulla attenuates the development of Ang II-induced hypertension in mice.

Design and method:

To test the hypothesis, we used inducible Tenascin-C-CreER2 and Agtr1a-floxed recombination approach to generate a novel mouse model with deletion of AT1a receptors selectively in the RMICs of the kidney (RMIC-Agtr1a-/-). Adult male wildtype (WT) and RMIC-Agtr1a-/- mice (n = 10 per group) were implanted with a telemetry probe and infused with or without Ang II via an osmotic minipump (∼500 μg/kg/day, i.p.) for 2 weeks.

Results:

Mice with deletion of AT1a receptors selectively in RMICs of the kidney medulla were fertile and grew normally without apparent structural or histological abnormality in the kidney medulla. However, telemetry systolic, diastolic, and mean blood pressure were significantly lower in adult male RMIC-Agtr1a-/- than WT mice (WT: 122 ± 4 mmHg vs. RMIC-Agtr1a-/-: 102 ± 3 mmHg, P < 0.01). Interestingly, this hypotensive phenotype in RMIC-Agtr1a-/- mice was associated with significant decreases in 24 h urine output (WT: 1.56 ± 0.15 mL/24 h vs. RMIC-Agtr1a-/-: 0.98 ± 0.13 mL/24 h, P < 0.01), urinary sodium (WT: 207.9 ± 7.3 μmol/24 h vs. RMIC-Agtr1a-/-: 145.2 ± 5.4 μmol/24 h, P < 0.01), and potassium excretion (WT: 221.0 ± 6.7 μmol/24 h vs. RMIC-Agtr1a-/-: 160.8 ± 10.6 μmol/24 h, P < 0.01), respectively. Moreover, urine osmolality was markedly decreased in RMIC-Agtr1a-/-mice (WT: 1724 ± 335 mOsm/Kg H2O vs. RMIC-Agtr1a-/-: 1128 ± 102 mOsm/Kg H2O, P < 0.01). Ang II infusion significantly increased telemetry systolic blood pressure to 148 ± 5 mmHg in WT mice, but it increased systolic blood pressure only to 129 ± 8 mmHg in RMIC-Agtr1a-/- mice (P < 0.01). Furthermore, infusion of Ang II for 2 weeks failed to restore urine osmolality in RMIC-Agtr1a-/- mice (1226 ± 110 mOsm/Kg H2O, n.s.).

Conclusions:

In conclusion, the results of the present study support the hypothesis that AT1a receptors in the RMICs of the kidney medulla plays a critical role in maintaining basal blood pressure homeostasis and the development of Ang II-induced hypertension.
LEVERAGING TELE-EDUCATION AS AN EFFECTIVE PLATFORM TO PROVIDE EASY ACCESS TO HEALTHCARE WORKERS ON HYPERTENSION MANAGEMENT IN SUB-SAHARAN AFRICA
Authors: Muktar Maryam , Dabiri Olabisi , Okeke Chika , Ogboye Ayoposi , Odukwe Adaora , Mobisson Nneka
Published: June 2023

Objective:

This study aims at showing the efficacy of using tele-education in making knowledge easily accessible to healthcare workers by using the University of New Mexico's Project ECHO® model. This model provides healthcare workers access to evidence-based knowledge to combat the challenges associated with sub-optimal training and depleting resources across Sub-Saharan Africa's healthcare system. This effort has led to significant improvement in the quality of healthcare service delivery.

Design and method:

Aggregate data were obtained from 4 Tele-education sessions conducted between August 2022- November 2022 to improve the capacity of Healthcare workers. Each session included a didactic presentation by a subject matter expert and a case study presentation by a healthcare worker. The case presentation involved citing real-life hypertension-related cases at the health facility to enable peer-to-peer learning exchange, as encouraged by the ECHO® model for Healthcare workers. The impacts of the sessions were measured using the pre and post-session tests to evaluate the knowledge gained by participants.

Results:

The population of this study was the 1,389 Healthcare workers from different cadres (such as doctors, nurses, midwives, lab scientists, Community Health Extension Workers (CHEWs), and mid-level managers) who joined the tele-education sessions. There was an average knowledge gain of 11.1%. Over 1.7 million indirect beneficiaries (patients) were reached through services provided by these trained Healthcare workers.

Conclusions:

The knowledge gained demonstrated the effectiveness of tele-education in improving the capacity of Healthcare workers to provide quality services in managing patients living with or at risk of hypertension. Tele-education cuts across most of the barriers encountered in spreading knowledge to healthcare workers and promotes health literacy and improved service delivery.
EFFECTS OF CAROTID BARORECEPTOR STIMULATION ON REGIONAL SYMPATHETIC ACTIVITY IN CHRONIC HEART FAILURE
Authors: Vanoli Jennifer , Dell’Oro Raffaella , Gronda Edoardo , Quarti-Trevano Fosca , Seravalle Gino , Grassi Guido
Published: June 2023

Objective:

Carotid baroreceptor stimulation (BAT) exerts in heart failure (CHF) sympatho-inhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behaviour.

Design and method:

In 9 CHF patients (age 58.3 ± 252 yrs, mean ± SD) we recorded via the microneurographic technique muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) before, 6 and 12 months following BAT. Measurements included left ventricular ejection fraction (LVEF), brain natriuretic peptide BNP (elisa), 6-minute walking test (6WT), New York Heart Association (NYHA) class, Minnesota score, together with routine laboratory variables. 10 age-matched CHF patients not underwent BAT served as controls.

Results:

BAT caused significant increase in LVEF (from 33.4 ± 5.1 to 37.1 ± 5.4%, P < 0.05) and in 6 WT, and a significant reduction in the Minnesota score and in NYHA class (from 3.3 ± 0.4 to 2.4 ± 0.4 a.u), unaltering BNP. MSNA, but not SSNA, was markedky activated in CHF. BAT caused a significant reduction in MSNA 6 and 12 months follow-up (from 70.7 ± 2.7 to 47.0 ± 4.3 and 44.1 ± 3.5 bursts/100heartbeats, means ± SD, P < 0.05). This effect was not accompanied by any significant change in SSNA (from 11.3 ± 2.1 to 11.5 ± 1.7 and 11.6 ± 2.1 bursts/minute, P = NS). A significant correlation was found between baseline MSNA values and the MSNA changes after BAT, which were also related to the LVEF modifications. No significant change in the various variables was detected in the control group followed for a 12 month observation.

Conclusions:

These data provide the first evidence that BAT exerts heterogeneous effects on sympathetic cardiovascular drive, inducing a marked reduction in MSNA but not in SSNA, which appears to be within the normal range in this condition. These effects may depend on the different reflex modulation regulating neuroadrenergic drive in these cardiovascular districts.
CHANGES IN ECHOCARDIOGRAPHIC INDICES FOLLOWING KIDNEY TRANSPLANTATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Betsikos Achilleas , Theodorakopoulou Marieta , Korogiannou Maria , Marinaki Smaragdi , Papagianni Aikaterini , Boletis John , Tsioufis Konstantinos , Sarafidis Pantelis
Published: June 2023

Objective:

Cardiovascular disease is the leading cause of death in ESKD and uremic cardiomyopathy contributes significantly to the increased cardiovascular risk in these patients. Kidney transplantation is associated with improved survival compared to dialysis. This systematic review and meta-analysis (CRD42022371202) aims to assess the changes in echocardiographic indices in patients before and following kidney transplantation

Design and method:

We included studies in adult subjects with echocardiographic assessments before (baseline) and following kidney transplantation (>1 month follow-up). The primary outcome measure was left-ventricular mass index (LVMI). Literature search involved PubMed, Web-of-Science and Scopus databases, manual search of article references and grey literature.

Results:

From 6463 records initially retrieved, 35 studies with a total of 2692 participants were included in the final quantitative meta-analysis. From 30 studies (2211 patients) reporting the primary outcome, LVMI was significantly decreased after kidney transplantation compared to pre-transplantation values [WMD -21.16 g/m2, 95%CI(-27.21, -15.12), I2 = 88%, P < 0.001]. In subgroup analysis, higher differences were evident among 6 studies (N = 163) evaluating LVMI < 6 months after kidney transplantation [WMD -41.54 g/m2, 95%CI (-51.31, -31.78), I2 = 13%, P < 0.001] and lower differences among 24 studies (N = 2048) evaluating LVMI >6 months after kidney transplantation [WMD -16.64 g/m2, 95%CI(-22.79, -10.49), I2 = 88%, P < 0.001]. In sensitivity analyses, patients receiving kidney from living kidney donors (WMD; -76.90 g/m2, 95%CI (-122.13, -31.67), I2 = 88%, P < 0.001) and those on hemodialysis before KTx [WMD;-33.76 g/m2, 95%CI (-51.51, -16.00), I2 = 92% P < 0.001] presented higher LVMI reductions following transplantation.

Conclusions:

Kidney transplantation is associated with significant reductions in LVMI compared to the pre-transplantation levels. This could be another factor contributing to the lower cardiovascular risk observed in KTRs compared to dialysis patients