Ocular biomarkers: useful incidental findings by deep learning algorithms in fundus photographs.

BACKGROUND/OBJECTIVES: Artificial intelligence can assist with ocular image analysis for screening and diagnosis, but it is not yet capable of autonomous full-spectrum screening. Hypothetically, false-positive results may have unrealized screening potential arising from signals persisting despite training and/or ambiguous signals such as from biomarker overlap or high comorbidity. The study aimed to explore the potential to detect clinically useful incidental ocular biomarkers by screening fundus photographs of hypertensive adults using diabetic deep learning algorithms. SUBJECTS/METHODS: Patients referred for treatment-resistant hypertension were imaged at a hospital unit in Perth, Australia, between 2016 and 2022. The same 45° colour fundus photograph selected for each of the 433 participants imaged was processed by three deep learning algorithms. Two expert retinal specialists graded all false-positive results for diabetic retinopathy in non-diabetic participants. RESULTS: Of the 29 non-diabetic participants misclassified as positive for diabetic retinopathy, 28 (97%) had clinically useful retinal biomarkers. The models designed to screen for fewer diseases captured more incidental disease. All three algorithms showed a positive correlation between severity of hypertensive retinopathy and misclassified diabetic retinopathy. CONCLUSIONS: The results suggest that diabetic deep learning models may be responsive to hypertensive and other clinically useful retinal biomarkers within an at-risk, hypertensive cohort. Observing that models trained for fewer diseases captured more incidental pathology increases confidence in signalling hypotheses aligned with using self-supervised learning to develop autonomous comprehensive screening. Meanwhile, non-referable and false-positive outputs of other deep learning screening models could be explored for immediate clinical use in other populations.

Therapeutic Inertia With Initial Low-Dose Quadruple Combination Therapy for Hypertension: Results From the QUARTET Trial.

BACKGROUND: Low-dose combinations are a promising intervention for improving blood pressure (BP) control but their effects on therapeutic inertia are uncertain. METHODS: Analysis of 591 patients randomized to an ultra-low-dose quadruple pill or initial monotherapy. The episode of therapeutic inertia was defined as a patient visit with a BP of >140/90 mm Hg without intensification of antihypertensive treatment. We compared the frequency of therapeutic inertia episodes between Quadpill and initial monotherapy as a proportion of the total population (intention-to-treat analysis with the denominator being all participants randomized) and as a proportion of people with uncontrolled BP (with the denominator being participants with uncontrolled BP). RESULTS: Therapeutic inertia occurred in fewer participants randomized to Quadpill compared with monotherapy. For example, among the 390 participants with a 6-month follow-up, therapeutic inertia according to unattended BP was 21/192 (11%) versus 45/192 (23%), P=0.002. There were similar rates of therapeutic inertia among those with uncontrolled unattended BP in each group (all P>0.4). Consistent observations were seen with the use of attended office BP measures. The major determinants of not intensifying treatment during follow-up were BP readings that were close to target and large improvements in BP compared with the previous visit. CONCLUSIONS: Among all treated individuals, low-dose Quadpill reduced the number of therapeutic inertia episodes compared with initial monotherapy. After the first follow-up visit, most high BP values did not lead to treatment intensification in both groups. Education is needed about the importance of treatment intensification despite a significant improvement in BP or BP being close to target. REGISTRATION: URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12616001144404; Unique identifier: ACTRN12616001144404.

Ambulatory blood pressure after 12 weeks of quadruple combination of quarter doses of blood pressure medication vs. standard medication.

BACKGROUND: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail. METHODS: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes. RESULTS: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P  < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P  < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P  < 0.001). The reduction in BP load was also more pronounced with the quadpill. CONCLUSION: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy.

Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis.

BACKGROUND: Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies. METHODS: A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically. RESULTS: In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed (P=0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P=0.0051). The observed reduction in estimated glomerular filtration rate across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up. CONCLUSIONS: Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.

Salt sensitivity risk derived from nocturnal dipping and 24-h heart rate predicts long-term blood pressure reduction following renal denervation.

BACKGROUND: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories. OBJECTIVES: We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort. METHODS: Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ±â€Š1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively. RESULTS: One-way ANOVA indicated a significant treatment effect ( P  = 0.03) between low ( n  = 15), moderate ( n  = 35), and high ( n  = 10) SSI risk with systolic BP reduction of 9.6 ±â€Š3.7 mmHg, 8.4 ±â€Š3.5 mmHg, and 28.2 ±â€Š9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P  = 0.18). High SSI risk independently correlated with systolic BP reduction ( P  = 0.02). CONCLUSIONS: Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts.

Trends in blood pressure changes and hypertension prevalence in Australian adults before and during the COVID-19 pandemic.

Efforts to limit the impact of the coronavirus disease (COVID-19) pandemic led to the implementation of public health measures and reallocation of health resources. To investigate trends in blood pressure (BP), hypertension and BMI in the Australian population during the COVID-19 pandemic, data from publicly accessible health stations were analyzed. Average BP and BMI measured by the SiSU Health Station network in Australia in over 1.6 million health screenings were compared between the years 2018 and 2021. Additionally, paired trajectories for BP and BMI development before and during the COVID-19 pandemic were calculated. Comparisons between pre-COVID years and post-COVID years of 2018 versus 2020, 2019 versus 2020, 2018 versus 2021, and 2019 versus 2021 showed increases in average adjusted systolic BP of 2.0, 1.7, 2.6, and 2.3 mmHg, respectively. Paired analysis of longitudinal data showed an overall increase in the trajectory of systolic BP of 3.2 mmHg between pre- and post-COVID years. The prevalence of hypertension in users of the health stations increased by approximately 25% in the years 2020-2021. Similar trends were seen for BMI. Data from public Australian health stations indicated a strong trend toward higher BP during the COVID-19 pandemic. At the population level, BP increments have been shown to markedly increase cardiovascular disease risk. Anti-pandemic measures need to be carefully evaluated in terms of secondary public health effects and health support systems extended to effectively target cardiovascular risk.

Taming resistant hypertension: The promise of novel pharmacologic approaches and renal denervation.

Resistant hypertension is associated with an exceedingly high cardiovascular risk and there remains an unmet therapeutic need driven by pathophysiologic pathways unaddressed by guideline-recommended therapy. While spironolactone is widely considered as the preferable fourth-line drug, its broad application is limited by its side effect profile, especially off-target steroid receptor-mediated effects and hyperkalaemia in at-risk subpopulations. Recent landmark trials have reported promising safety and efficacy results for a number of novel compounds targeting relevant pathophysiologic pathways that remain unopposed by contemporary drugs. These include the dual endothelin receptor antagonist, aprocitentan, the aldosterone synthase inhibitor, baxdrostat and the nonsteroidal mineralocorticoid receptor antagonist finerenone. Furthermore, the evidence base for consideration of catheter-based renal denervation as a safe and effective adjunct therapeutic approach across the clinical spectrum of hypertension has been further substantiated. This review will summarise the recently published evidence on novel antihypertensive drugs and renal denervation in the context of resistant hypertension.

Cost-effectiveness of ultra-low-dose quadruple combination therapy for high blood pressure.

OBJECTIVE: To determine the cost-effectiveness and cost-utility of a quadpill containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg and bisoprolol 2.5 mg in comparison with irbesartan 150 mg for people with hypertension who are either untreated or receiving monotherapy. METHODS: We conducted a within-trial and modelled economic evaluation of the Quadruple UltrA-low-dose tReaTment for hypErTension trial. The analysis was preplanned, and medications and health service use captured during the trial. The main outcomes were incremental cost-effectiveness ratios (ICERs) for cost per mm Hg systolic blood pressure (BP) reduction at 3 months, and modelled cost per quality-adjusted life year (QALY) over a lifetime. RESULTS: The within-trial analysis showed no clear difference in cost per mm Hg BP lowering between randomised treatments at 3 months ($A10 (95% uncertainty interval (UI) $A -18 to $A37) per mm Hg per person) for quadpill versus monotherapy. The modelled cost-utility over a lifetime projected a mean incremental cost of $A265 (95% UI $A166 to $A357) and a mean 0.02 QALYs gained (95% UI 0.01 to 0.03) per person with quadpill therapy compared with monotherapy. Quadpill therapy was cost-effective in the base case (ICER of $A14 006 per QALY), and the result was sensitive to the quadpill cost in one-way sensitivity analysis. CONCLUSIONS: Quadpill in comparison with monotherapy is comparably cost-effective for short-term BP lowering. In the long-term, quadpill therapy is likely to be cost-effective. TRIAL REGISTRATION NUMBER: ANZCTRN12616001144404.

Catheter-Based Renal Denervation: 9-Year Follow-Up Data on Safety and Blood Pressure Reduction in Patients With Resistant Hypertension.

BACKGROUND: Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU). METHODS: We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU. RESULTS: A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg (P<0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg (P<0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline (P=0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m2. Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU (P<0.0001). CONCLUSIONS: RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.

Stagnating rates of blood pressure control in Australia: insights from opportunistic screening of 10 046 participants of the May Measurement Month campaigns.

BACKGROUND: Raised blood pressure (BP) remains the single most important modifiable risk factor contributing to cardiovascular and all-cause mortality in Australia and worldwide. May Measurement Month , a global BP measurement and screening campaign initiated by the International Society of Hypertension and carried out in Australia since its inception in 2017, aimed at obtaining standardized BP measurements from members of the community to increase awareness of high BP and its associated risks. METHOD: Adults participants (≥18 years) were recruited through opportunistic sampling across Australia during the month of May in 2017, 2018 and 2019. Trained volunteers recorded BP readings in a standardized manner and collected data on demographic, lifestyle factors and comorbidities. Hypertension was defined as SBP of at least 140 mmHg, or DBP of at least 90 mmHg, or taking antihypertensive medication. Data were collated centrally and analysis was carried out using regression models to evaluate the associations between BP and participant characteristics. RESULTS: A total of 10 046 participants were screened, of whom 3097 (31.0%) had hypertension, only 48.5% were aware of their condition and 44.4% were taking antihypertensive medication. Of those taking antihypertensive medication, 53.2% were controlled to less than 140/90 mmHg, whereas the remaining 46.8% of participants had BP of at least 140/90 mmHg suggestive of inadequately treated hypertension. CONCLUSION: Consecutive data obtained over a 3-year period in Australia demonstrated stagnating awareness, treatment and control rates with the latter two being substantially lower than global rates and those in other high-income countries. Concerted efforts from all stakeholders will be required to help overcome the unacceptably poor rates of BP treatment and control in Australia.

Evaluation of Circulating Platelet Extracellular Vesicles and Hypertension Mediated Organ Damage.

Elevated circulating platelet-derived extracellular vesicles (pEVs) have been associated with arterial hypertension. The role of hypertension-mediated organ damage (HMOD) to induce EV release is still unknown. We studied the micro- and macro-vascular changes (retinal vascular density and pulse wave velocity), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), and assessed the psychosocial status (anxiety and depression) in hypertensive patients to determine their relationship with EV release. Pulse wave velocity showed a significant positive correlation with pEVs (r = 0.33; p = 0.01). Systolic blood pressure (SBP) negatively correlated with retinal vascularity. The superficial retinal vascular plexus density in the whole image showed a significant negative correlation with 24 h SBP (r = −0.38, p < 0.01), day-SBP (r = −0.35, p = 0.01), and night-SBP (r = −0.27, p = 0.04). pEVs did not show significant associations with microvascular damage (retinal vascular density), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), or psychosocial status (anxiety and depression). Our results indicate that the pEV levels were associated with macrovascular damage measured by PWV, whereas no significant association between pEVs and microvascular damage, endothelial function, or emotional status could be detected. The potential utility of pEV in clinical practice in the context of HMOD may be limited to macrovascular changes.

Association of Circulating Platelet Extracellular Vesicles and Pulse Wave Velocity with Cardiovascular Risk Estimation.

Elevated circulating platelet-derived extracellular vesicles (EVs) have been reported in conditions associated with thrombotic risk. The present study aimed to assess the relationship between circulating platelet-derived EV levels, cardiovascular risk stratification and vascular organ damage, as assessed by pulse wave velocity (PWV). A total of 92 patients were included in the present analysis. Platelet EV were evaluated by flow cytometry (CD41+/Annexin v+). The cardiovascular risk was determined using the 2021 ESC guideline stratification and SCORE2 and SCORE-OP. PWV was performed as a surrogate to assess macrovascular damage. Risk stratification revealed significant group differences in EV levels (ANOVA, p = 0.04). Post hoc analysis demonstrated significantly higher levels of EVs in the very high-risk group compared with the young participants (12.53 ± 8.69 vs. 7.51 ± 4.67 EV/µL, p = 0.03). Linear regression models showed SCORE2 and SCORE-OP (p = 0.04) was a predictor of EV levels. EVs showed a significant association with macrovascular organ damage measured by PWV (p = 0.01). PWV progressively increased with more severe cardiovascular risk (p < 0.001) and was also associated with SCORE2 and SCORE-OP (p < 0.001). Within the pooled group of subjects with low to moderate risk and young participants (<40 years), those with EV levels in the highest tertile had a trend towards higher nocturnal blood pressure levels, fasting glucose concentration, lipid levels, homocysteine and PWV. Levels of platelet-derived EVs were highest in those patients with very high CV risk. Within a pooled group of patients with low to moderate risk, an unfavourable cardiometabolic profile was present with higher EV levels.

Impact of various night-time period definitions on nocturnal ambulatory blood pressure.

BACKGROUND: Several definitions of night-time BP exist for the calculation of nocturnal blood pressure (BP) based on 24-h BP measurements. How much these methods differ regarding the resulting nocturnal blood pressure values, under which circumstances these differences become clinically meaningful, and under which circumstances diary-adjusted measurements should be used preferentially remains uncertain. METHODS: Data of 512 24-h BP recordings were analysed regarding differences in nocturnal BP based on three alternative definitions of night-time: 2300-0700 h, 0100-0500 h, and diary-adjusted measures. RESULTS: Mean systolic nocturnal BP between 2300-0700 h was 2.5 mmHg higher than between 0100 and 0500 h and 1.6 mmHg higher than diary adjusted estimates. Up to 38.3% of individuals showed BP differences of more than 5 mmHg when comparing temporal definitions of night-time, resulting in significant proportions of individuals being re-classified as hypertensive. When diary-derived sleeping patterns differed by less than 2 h from the 2300 to 0700 h fixed time definition, mean BP discrepancies remained below 3 mmHg. Absolute time discrepancies between diary and 2300-0700 h fixed time definition of 2-4, 4-8 or at least 8 h led to SBP/DBP differences of 4.1/3.1, 6.8/6.1, and 14.5/9.1mmHg, respectively. CONCLUSION: Average differences of nocturnal BP between varying definitions in study/cohort data are small and would be of limited relevance in many settings. However, substantial differences can be observed in individual cases, which may affect clinical decision-making in specific patients. In patients whose sleeping patterns differs by more than 2 h from defined fixed night-times, diaries should be used for adjustment.

Platelet-derived extracellular vesicles correlate with therapy-induced nocturnal blood pressure changes.

INTRODUCTION: Elevated nocturnal blood pressure (BP) is closely associated with increased risk of cardiovascular (CV) events. Circulating extracellular vesicles (EVs) have been proposed as a potential CV risk biomarker and shown to correlate with BP. The present study aimed to assess whether a reduction in BP is paralleled by respective changes in EVs. METHODS: Fifty-five hypertensive patients (age: 57.7 ±â€Š14.1 years) were included in the study. EVs and BP were assessed at baseline and at 12 weeks follow-up. Interventions to lower BP included advice on life-style modification only or life-style advice combined with additional pharmacotherapy. EVs were evaluated by flow cytometry (CD41+/Annexin V+) and BP by unobserved automated office BP and ambulatory BP monitoring. RESULTS: Nocturnal systolic BP correlated with EV levels at baseline ( P  = 0.01). Multivariable regression models showed that changes in nocturnal systolic BP (adjusted R2  = 0.23; P  = 0.01) and diastolic BP (adjusted R2  = 0.18; P  = 0.02) were associated with respective changes in EV levels. Furthermore, intervention-induced improvement of systolic dipping was associated with a reduction in EVs in the univariate analysis (adjusted R2  = 0.06; P  = 0.03). In contrast, systolic office, 24 h- and daytime-BP did not show significant associations with EVs. Patients whose medication was up-titrated at baseline showed a trend towards lower EV levels at follow-up (absolute change of -1.7 ±â€Š1.3 EV/µl; P  = 0.057). CONCLUSIONS: Circulating platelet-derived EVs were positively associated with nocturnal BP and therapy-induced changes over a 12-week treatment period. EVs may provide an integrated measure of BP changes achieved with pharmacotherapy.

Circulating short-chain fatty acids in hypertension: a reflection of various hypertensive phenotypes.

BACKGROUND: Hypertension is the most common chronic condition globally, contributing to an increased risk of cardiovascular disease and premature death. Despite advances in treatment options, approximately 10% of patients have resistant hypertension, characterized by elevated blood pressure that does not respond to treatment. The gut microbiome is now increasingly recognized to play a role in the development and pathogenesis of several diseases, including hypertension, although the exact mechanisms remain unclear. METHOD: The aim of the present study was to investigate circulating levels of short-chain fatty acids, metabolites produced by gut bacteria, in essential ( n  = 168) and resistant hypertensive ( n  = 27) patients, compared with healthy controls ( n  = 38). RESULTS: Serum acetate was significantly lower in the resistant hypertensive population, compared with both the normotensive controls and those with essential hypertension (748 ±â€Š89 versus 1335 ±â€Š61 and 1171 ±â€Š22 nmol/ml, P  < 0.0001). Acetate was also significantly lower in treated versus untreated hypertensive patients or controls (1112 ±â€Š27 versus 1228 ±â€Š40 and 1327 ±â€Š63 nmol/l, P  < 0.01), with this finding more pronounced with increasing number of antihypertensive therapies. In contrast, propionate was lower and butyrate significantly higher in those with essential hypertension compared with controls (propionate: 25.2 ±â€Š7.5 versus 58.6 ±â€Š7.6 nmol/ml, P  < 0.0001; butyrate: 46.5 ±â€Š3.5 versus 14.7 ±â€Š9.9 nmol/ml, P  < 0.01). A novel and perhaps clinically relevant observation was the significant difference in acetate and propionate levels between patients taking ACE inhibitors or angiotensin-receptor blockers. CONCLUSION: The present study has highlighted differences in circulating short-chain fatty acids in different hypertensive phenotypes and a possible influence of drug number and class. Although further research is necessary, this may represent a novel therapeutic target, particularly in patients with resistant hypertension.

Circulating platelet-derived extracellular vesicles correlate with night-time blood pressure and vascular organ damage and may represent an integrative biomarker of vascular health.

Elevated office blood pressure (BP) has previously been associated with increased levels of circulating extracellular vesicles (EVs). The present study aimed to assess the relationship between levels of platelet derived EVs, ambulatory BP parameters, and pulse wave velocity as a marker of macrovascular organ damage. A total of 96 participants were included in the study. Platelet-derived extracellular vesicles (pEVs) were evaluated by flow cytometry (CD41+/Annexin v+). BP evaluation included unobserved automated office BP and ambulatory BP monitoring. Carotid-femoral pulse wave velocity (PWV) was measured as a marker of macrovascular damage. pEVs correlated with nocturnal systolic BP (r = 0.31; p = .003) and nocturnal dipping (r = -0.29; p = .01) in univariable analysis. Multivariable regression models confirmed robustness of the association of EVs and nocturnal blood pressure (p = .02). In contrast, systolic office, 24h- and daytime-BP did not show significant associations with pEVs. No correlations were found with diastolic BP. Circulating pEVs correlated with pulse wave velocity (r = 0.25; p = .02). When comparing different hypertensive phenotypes, higher levels of EVs and PWV were evident in patients with sustained hypertension compared to patients with white coat HTN and healthy persons. Circulating platelet derived EVs were associated with nocturnal BP, dipping, and PWV. Given that average nocturnal BP is the strongest predictor of CV events, platelet derived EVs may serve as an integrative marker of vascular health, a proposition that requires testing in prospective clinical trials.

Global Impact of Different Blood Pressure Thresholds in 4 021 690 Participants of the May Measurement Month Initiative.

BACKGROUND: Influential guidelines currently define hypertension at different thresholds of blood pressure (BP). The global May Measurement Month initiative provides a unique opportunity to estimate the potential consequences of universal lowering of BP thresholds on the prevalence of hypertension based on a large, real-world, patient-level data set. METHODS: The average of the second and third of 3 attended BP readings after 5 minutes of rest from 4 021 690 standardized, opportunistic BP screenings in various settings of the 2017 to 2019 May Measurement Month initiatives from 104 countries were analyzed to assess the demographic and phenotypic impact of 3 defined BP thresholds. RESULTS: The age- and sex-standardized median of the relative increase in rate of hypertension with a change of thresholds from ≥140/≥90 to ≥130/≥80 mm Hg was 72.3% (interquartile range, 59.3%-91.3%) among the participating countries. With a change from ≥140/≥90 to ≥120/≥70 mm Hg, the median range was 162.6% (interquartile range, 132.8%-202.6%). The increase in rate of hypertension was most pronounced in low-income (95.3% and 203.9%) and least pronounced in high-income countries (71.6% and 167.1%). CONCLUSIONS: The impact of a universal application of lower BP thresholds for the definition of hypertension would have an enormous impact on the prevalence of hypertension globally with large disparities between countries and substantial heterogeneity of demographic and phenotypic patterns, which should be confirmed in dedicated population studies. While focusing on lower BP targets may constitute an opportunity for early intervention, the potential socioeconomic consequences may pose unsurmountable obstacles for most health care systems worldwide.

Retinal Capillary Damage Is Already Evident in Patients With Hypertension and Prediabetes and Associated With HbA1c Levels in the Nondiabetic Range.

OBJECTIVE: We analyzed whether any change in capillary density in the retinal circulation could be detected in patients with hypertension in the prediabetic stage. RESEARCH DESIGN AND METHODS: In a cross-sectional analysis, we assessed capillary density in the foveal (CDF) and parafoveal retinal areas using optical coherence tomography-angiography in 62 patients with hypertension and normal glucose metabolism and 40 patients with hypertension and prediabetes. RESULTS: The CDF was lower in patients with prediabetes than in those with normal glucose metabolism. Moreover, we found a correlation between CDF and HbA1c and glucose levels for the entire cohort. In patients with HbA1c <6.5% (48 mmol/mol), CDF was lower in patients with HOMA for insulin resistance (HOMA-IR) ≥2.5 than in patients with HOMA-IR <2.5. CONCLUSIONS: Patients with hypertension and prediabetes display retinal capillary changes, and an association with markers of glucose metabolism exists, even within a nondiabetic HbA1c range.