Hypertension-mediated Organ Damage Research Articles

High normal blood pressure and left ventricular structural and functional disorders in young adults

Aim. To evaluate the association of a high normal blood pressure (BP) with the risk of early hypertension-mediated organ damage (HMOD) in young adults.Material and methods. Medical screening of population aged 18-45 years (n=987) revealed that in 173 persons, office BP corresponded to a high normal level or hypertension (HTN). Echocardiography (GE Healthcare Vivid 9, using EchoPAC Software) was performed when HTN was confirmed by office BP measurement and/or according to 24-hour ambulatory BP monitoring (ABPM) (n=127). In addition, creatinine and albumin-to-creatinine ratio in spot urine were measured.Results. The median age was 23 [21; 25] years. The median systolic (SBP) and diastolic BP (DBP) was 129 [121; 137] and 75±12 mm Hg, respectively. The detection rate of LV geometry abnormalities was 3,3 times higher in the high normal BP group [95% CI, 1,06-6,28, p=0,02], and 10,7 times higher in the HTN group [95% CI, 2,32-16,49, p=0,04] compared with the optimal+normal BP group. In a multivariate analysis, the independence of associations with the LV mass index (LVMI) was confirmed only for the mean nighttime DBP, left atrial volume index, and the ratio of LV peak early diastolic velocity to the average septal and lateral peak early diastolic mitral annular velocity.Conclusion. In young people, the prevalance of HMOD is comparable in the groups with high normal BP and HTN, while significant differences were found between the group with optimal+normal BP levels and patients with HTN and high normal BP. An independent association of elevated LVMI with mean nighttime DBP was found.

Elevated Th17 cell proportion, related cytokines and mRNA expression level in patients with hypertension-mediated organ damage: a case control study.

BackgroundImmune abnormalities and inflammatory responses play critical roles in progression of hypertension. Basic studies have confirmed that Th17 cell and related cytokines are important in promoting hypertension-mediated organ damage, but few clinical evidences have been published. Therefore, our study aimed to investigate the relationship between Th17 cell and its related cytokines and hypertension-mediated organ damage in human.MethodsThis study enrolled 179 patients with hypertension (including 92 with hypertension-mediated organ damage and 87 without hypertension-mediated organ damage) and 63 healthy participants. The proportion of Th17 cells in peripheral blood mononuclear cells was measured by flow cytometry. The concentrations of interleukin-17 and interleukin-23 were detected by enzyme-linked immunosorbent assay. Real time-polymerase chain reaction was used to detect the mRNA expression levels of interleukin-17, retinoic acid-related orphan receptor (ROR) γt and signal transducer and activator of transcription-3 (STAT-3).ResultsThe proportion of Th17 cells, the concentration of interleukin-17 and interleukin-23 and the mRNA expression levels of interleukin-17, retinoic acid-related orphan receptor γt and signal transducer and activator of transcription-3 were significantly increased in hypertension-mediated organ damage group compared with those in non-hypertension-mediated organ damage group and control group (P < 0.005).ConclusionTh17 cells and their associated cytokines may be involved in hypertension-mediated organ damage formation and may be able to serve as new biomarkers of hypertension-mediated organ damage and potential therapeutic targets.

ISOLATED DIASTOLIC HYPERTENSION IS NOT A BENIGN SITUATION REGARDING HYPERTENSION MEDIATED ORGAN DAMAGE IN PATIENTS WITH FIRST DIAGNOSED AND NEVER TREATED ESSENTIAL HYPERTENSION

Isolated diastolic hypertension (IDH) usually remains untreated as it is considered benign compared to isolated systolic or combined systolic/diastolic hypertension. Hypertension mediated organ damage (HMOD) needs to be assessed in each individual hypertensive patient in order to estimate cardiovascular risk. We aimed to investigate the HMOD differences between first diagnosed and never treated patients with IDH compared to normotensive subjects.We studied 68 non-diabetic, first diagnosed and never-treated hypertensive patients with IDH (mean age = 49 + 9, 65% males, 24% smokers) and 30 normotensives (mean age = 51 + 10, 17% males, 20% smokers). Office and ambulatory blood pressure monitoring (24 h ABPM), CV risk factors [smoking, obesity (BMI), hyperlipidemia and HMOD [aortic stiffness (PWV), left ventricular diastolic dysfunction (EEa), cardiac hypertrophy (LVMI), coronary arteries microcirculation (CFR), carotid intima-media thickness (cIMT) were estimated in each hypertensive patient as well as normotensive subject.IDH patients had similar age, BMI and smoking habit, decreased LDL-C and increased diastolic (89 + 9 vs. 84 + 9 mmHg, p = 0.02) and mean office BP (106 + 9 vs. 99 + 12 mmHg, p = 0.01) as well as 24 h systolic (126 + 3 vs. 119 + 6 mmHg, p < 0.001) and diastolic ABPM (84 + 4 vs. 73 + 4 mmHg, p < 0.001) compared to normotensives. Regarding HMOD, IDH patients had increased LVMI (78 + 17 vs. 68 + 19 g/m2, p = 0.03) and IMT (0.9 + 0.1 vs. 0.8 + 0.1 mm, p = 0.03) but similar PWV, E/Ea and CFR compared to normotensives. LVMI was related to diastolic (r = 0.32, p = 0.008) and mean (r = 0.32, p = 0.01) office BP in IDH patients.The presence of HMOD in patients with first diagnosed and never treated IDH underscores the need for antihypertensive treatment (life style changes and medication). As HMOD may regress with successful antihypertensive treatment, there is still time for physicians to reduce future CV events in those patients.

HEPATIC STEATOSIS INDEX IS INDEPENDENTLY RELATED TO HYPERTENSION MEDIATED ORGAN DAMAGE IN PATIENTS WITH FIRST DIAGNOSED AND NEVER TREATED ESSENTIAL HYPERTENSION AND SMOKING HABIT

Non-alcoholic fatty liver disease (NAFLD) is closely related to the metabolic syndrome, arterial hypertension and overall cardiovascular (CV) disease. We aimed to investigate if those first diagnosed and never-treated patients with essential hypertension at high risk for NAFLD, measured by the Hepatic Steatosis Index (I), already have an impaired CV risk profile estimated by increased blood pressure burden and accompanied by the presence of hypertension-mediated organ damage (HMOD).We studied 254 non-diabetic, first diagnosed and never-treated young hypertensive patients, [mean age=51 + 11 years, 59% males, 31% smokers]. Ambulatory blood pressure monitoring (24 h ABPM), CV risk factors [smoking, obesity (BMI), hyperlipidemia and HMOD [aortic stiffness (PWV), left ventricular diastolic dysfunction (EEa), cardiac hypertrophy (LVMI), coronary arteries microcirculation (CFR), carotid intima-media thickness (cIMT) and endothelial dysfunction (PBR5-25)] were estimated in each patient before treatment initiation. HIS was calculated as 8 times (ALT/AST ratio) + BMI (+2, if female; + 2, if diabetes mellitus).The whole hypertensive population was divided regarding I median value=39.3 in Group A (high risk NAFLD group, n = 127, age = 50 + 10) and Group B (low risk NAFLD group, n = 127, age = 52 + 11). Group A had increased BMI (32 + 5 vs. 27 + 3, p < 0.001), systolic night-time ABPM (128 + 15 vs. 124 + 11, p = 0.04), Chol (217 + 40 vs. 206 + 35, p = 0.01) and Trigl (141 + 79 vs. 112 + 65, p = 0.002), E/Ea (7 + 2 vs. 6 + 2, p = 0.4) and LVMI (83 + 17 vs. 79 + 15, p = 0.03) compared to Group B while all other studied demographic/laboratory/ABPM/HMOD parameters (PWV, MAU, CFR and cIMT) were similar. I was related to BMI (p < 0.001) and office BP, systolic (p < 0.001) and diastolic (p = 0.01), in total population as well as to LVMI (r = 0.24, p = 0.03) in smokers. Finally, in multiple regression analysis, we noted that I was independently associated with LVMI (beta = 0.28, p = 0.05) only in male smokers.Our findings underscore the augmented CV risk (smoking, obesity, hyperlipidemia, BP burden and HMOD) in people with first diagnosed arterial hypertension who are at high risk for NAFLD. As successful antihypertensive treatment may lead to HMOD regression, there is still time for those patients to be treated for hypertension disease and hyperlipidemia and quit smoking, in order to reduce future CV risk.

SMOKING HABIT IS NOT RELATED WITH HYPERTENSION MEDIATED ORGAN DAMAGE IN YOUNG PATIENTS WITH FIRST DIAGNOSED AND NEVER TREATED ESSENTIAL HYPERTENSION

Early onset arterial hypertension (AH) is associated with a considerably increased risk for cardiovascular (CV) disease. Cigarette smoking represents a significant CV risk factor. Aim of this study is the investigation of any differences between smokers and non smokers first diagnosed and never treated young patients with essential hypertension regarding the burden of blood pressure and the presence of hypertension-mediated organ damage (HMOD).We studied 272 non-diabetic, first diagnosed and never-treated young hypertensive patients, [median age=43(39-48), 68% males]. Ambulatory blood pressure monitoring (24 h ABPM), CV risk factors [smoking, obesity (BMI), hyperlipidemia and HMOD [aortic stiffness (PWV), left ventricular diastolic dysfunction (EEa), cardiac hypertrophy (LVMI), coronary arteries microcirculation (CFR), carotid intima-media thickness (cIMT) and endothelial dysfunction (PBR5-25)] were estimated in each young patient before treatment initiation.Young patients' population was divided regarding smoking habit in smokers group [n = 105, age = 43(38-47), 75 males)] and non-smokers [n = 167, age = 43 (39-48), 119 males]. LDL-C levels, triglycerides, 24 h and daytime systolic ABPM, systolic and diastolic BP variability (BPV) and systolic BP load (BPL) during daytime were increased in smokers compared to non-smokers. No significant differences between smokers and non-smokers regarding age, BMI, E/Ea, LVMI, PWV, MAU, CFR, cIMT and PBR5-25 were found. However, the incidence of LVH (13% vs. 6%, p = 0.04) and impaired CFR (p = 0.05) was increased in smokers compared to non-smokers. In multiple regression analysis, we noted that 24 h systolic ABPM was independently associated with PWV (beta = 0.31, p < 0.001), LVMI (beta = 0.32, p < 0.001) and CFR (beta = -0.18, p = 0.01) regardless of smoking habit.In young people with first diagnosed arterial hypertension, HMOD is independently related to BP burden, irrespective of smoking habit. As HMOD may regress with successful antihypertensive treatment, there is still time for those young patients to treat hypertension disease and hyperlipidemia and quit smoking, in order to reduce future CV risk.

RELATIONSHIP BETWEEN COGNITIVE IMPAIRMENT AND HYPERTENSION MEDIATED ORGAN DAMAGE: THE VOBARNO STUDY

Background Several studies have suggested the presence of a relationship between hypertension in mid-life and the subsequent development of mild cognitive impairment (MCI) and dementia.Aim: to analyze the relationship between baseline blood pressure (BP), cardiovascular risk factors and presence of Hypertension Mediated Organ Damage (HMOD) and cognitive performances oppler after a follow-up period of 12 years in 149 subjects participating into the Vobarno Study.149 subjects (52% female, mean age 54.9 ± 8, 9 ± 3.25 school years, 59% hypertensives) underwent blood chemistry, arterial pressure measurement, echocardiography, carotid oppler ultrasound and measurement of central arterial pressure (PWA) and carotid-femoral pulse wave velocity (PWV). All subjects underwent a neuropsychological evaluation with standardized tests performed at a follow-up visit 12 years later.57 subjects with MCI at follow-up had baseline higher arterial pressure values (SBP and PP clinical and 24 h p < 0.05), IMT (1.23 ± 0.34 vs 1.12 ± 0.25 p < 0.05), and PWV (11.45 ± 3.37 m/sec vs 10.49 ± 1.74 p < 0.05) than those observed in the 92 subjects without MCI. Subjects with MCI were divided in two groups according to presence of amnesia (18 and 21% of total, respectively). Baseline IMT was significantly higher in subjects who developed non-amnesic MCI when compared with patients without MCI (Meanmax 1.30 ± 0.36 mm vs 1.12 ± 0.25 mm p < 0.05; CBmax 1.30 ± 0.29 mm vs 1.16 ± 0.24 mm p < 0.05); no differences were found between amnesic and nonamnesic subjects.our results show that baseline presence of hypertension and HMOD may be associated with cognitive performance detected after a mean period of 10 years. Aortic stiffness (measured as PWV) appears to be a less sensitive predictor of cognitive decline than increased IMT.

INFLAMMATORY MARKERS AND HYPERTENSION-MEDIATED ORGAN DAMAGE IN COMMUNITY-DWELLING ELDERLY INDIVIDUALS: THE NORTHERN SHANGHAI STUDY

Inflammation plays a role in pathogenesis of atherosclerosis. Many inflammatory makers have proven to can predict cardiovascular events. This study is investigating the association between inflammatory makers and hypertension-mediated organ damage.2451 participants who had available blood routine examination from the Northern Shanghai Study were included in this analysis. Inflammatory makers include white blood cell (WBC), neutrophile, monocyte and monocyte to high-density lipoprotein cholesterol ratio (MHR). Hypertension-mediated organ damage (HMOD), including left ventricular hypertrophy (LVH), arterial stiffness (AS), lower extremity atherosclerotic (LEA), carotid hypertrophy (CH), micro-albuminuria (MAU) and chronic kidney disease (CKD), were measured by standard methods. Logistic regression model was used to explore the relationship between the quartiles of inflammatory makers and HOMD.In multivariable logistic regression analysis, set quartile 1 (Q1) as reference, quartile 4 (Q4) of WBC (odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.31-2.24, Pfor trend < 0.001), neutrophile (OR = 1.48, 95%CI:1.14-1.94, Pfor trend = 0.005), monocyte (OR = 1.37, 95%CI:1.05-1.77, Pfor trend = 0.026) and MHR (OR = 1.41, 95%CI:1.05-1.88, Pfor trend = 0.036) were associated with AS; Q4 of WBC (OR = 1.78, 95%CI:1.24-2.58, Pfor trend = 0.001), neutrophile (OR = 2.06, 95%CI:1.40-3.02, Pfor trend < 0.001), monocyte (OR = 1.64, 95%CI:1.11-2.38, Pfor trend = 0.013) and MHR (OR = 2.23, 95%CI:1.49-3.35, Pfor trend < 0.001) were associated with LEA; Q4 of WBC (OR = 1.60, 95%CI:1.13-2.27, Pfor trend = 0.012), neutrophile (OR = 1.74, 95%CI:1.21-2.51, Pfor trend = 0.002), monocyte (OR = 1.71, 95%CI:1.18-2.46, Pfor trend = 0.013) and MHR (OR = 2.46, 95%CI:1.60-3.77, Pfor trend < 0.001) were associated with CKD; Q4 of monocyte (OR = 0.69, 95%CI:0.54-0.87, Pfor trend < 0.001) and MHR (OR = 0.61, 95%CI:0.47-0.79, Pfor trend < 0.001) were inversely associated with MAU; but no inflammatory markers associated with LVH or CH.In Chinese community-dwelling elderly individuals, WBC, neutrophile, monocyte and MHR are significantly and independently associated with an increased risk of AS, LEA and CKD; monocyte and MHR inversely associated an increased risk of MAU.

CIRCADIAN BLOOD PRESSURE PROFILE IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION

Disturbed circadian blood pressure (BP) profile is a risk factor for cardiovascular complications in adults. The study aimed to evaluate factors affecting circadian BP profile and its association with hypertension-mediated organ damage (HMOD) in pediatric patients with primary hypertension (PH).The study included 112 children (79 boys, 33 girls, 14.7 ± 2.7 years) with untreated PH. Circadian BP profile was assessed by 24-hour ABPM. Disturbed circadian BP profile (non-dipping) was defined as a nocturnal drop in systolic or diastolic BP (SBP, DBP) < 10%. A nocturnal drop in SBP or DBP > 20% was defined as extreme dipping. Patients were evaluated for central BP, HMOD (left ventricular mass index - LVMI, aortic pulse wave velocity, augmentation index (AIx75HR), intima-media thickness, albuminuria), and clinical and biochemical parameters, including sodium-potassium balance.In the study group, the mean nocturnal drop in SBP was 10.9 ± 5.9 [%] and in DBP - 16.2 ± 8.5 [%]. Non-dipping was found in 50 (44.6%) children and extreme-dipping in 29 (25.9%) patients. The nocturnal drop in SBP correlated negatively with Z-scores of body weight (r = -0.191, p = 0.043) and BMI (r = -0.242, p = 0.010) and with LVMI [g/m2.7] (r = -0.395, p = 0.006). The nocturnal drop in SBP and DBP correlated positively with urinary potassium excretion [mmol/kg/24 h] (r = 0.656, p = 0.001 and r = 0.540, p = 0.011, respectively). Patients with disturbed circadian blood pressure profile were characterized by higher LVMI (44.5 ± 12.5 vs. 36.8 ± 8.8 [g/m2.7]) and albuminuria (median: 10.8, IQR: 5.3-53.3 vs. median: 8.1, IQR: 5.5-16.4 [mg/24 h], p = 0.043) and lower urinary potassium excretion (0.6 ± 0.2 vs. 1.1 ± 0.3 [mmol/kg/24 h]). Extreme-dipping patients had a higher AIx75HR than the other patients (median: + 3.3, IQR: -6.3- + 17.7 vs. -4.6, IQR: -17.3- + 4.0 [%], p = 0.048).1. Disturbed circadian BP profile is common in children with PH and should not be considered a marker of secondary hypertension.2. Disturbed circadian BP profile may be associated with higher body weight and lower dietary potassium intake.3. Pediatric patients with PH and disturbed BP profile are at risk for HMOD: left ventricular hypertrophy and microalbuminuria.4. Extreme-dipping may be associated with increased arterial stiffness in children with PH.

VASCULAR AGE IN ADOLESCENTS WITH PRIMARY HYPERTENSION

There is evidence that children with primary hypertension (PH) are more mature than their normotensive peers in terms of bone and the immune system age. The aim of our study was to evaluate vascular age and its relationship with hypertension-mediated organ damage (HMOD) in adolescents with PH.We assessed 362 children [90 girls; 15.5 (13.9;16.8) years] referred for work-up of office hypertension and 64 normotensive (NT) subjects [12 girls; 14.5 (13.8;15.6) years] not different in terms of age, body mass (BM) and BMI. We analyzed age- and height-related pulse wave velocity (PWV); the expected vascular age (based on measured PWV) was obtained from pooled pediatric and adult PWV norms and the difference (VascAgeDiff) between the vascular and chronological age was calculated. In all patients we obtained ambulatory blood pressure monitoring (ABPM) and HMOD: left ventricular mass index (LVMi), carotid intima-media thickness (cIMT) and pulse wave analysis (PWA) parameters: stroke volume (SV), cardiac output (CO), aortic BP (AoBP), total peripheral resistance (TPR).Based on office, ABPM and AoBP, patients were classified into white coat hypertension (WCH) - 166 patients, ambulatory prehypertension (AmbPreHT) - 32; spurious hypertension (sHT - isolated systolic hypertension and normal AoBP) - 55; true hypertension (tHT - elevated office, ambulatory and AoBP) - 99. VascAgeDiff progressively increased from NT through sHT, WCH, AmbPreHT to tHT (3.5; 6.2; 7.2; 10.0; 10.7 years; p < 0.01). VascAgeDiff correlated (univariate analysis) significantly with weight, BMI z-score, office systolic (SBP) and diastolic blood pressure (DBP), AoBP, 24-h mean arterial pressure, 24-h DBP, CO, serum uric acid and LDL cholesterol level (p < 0.05). Multivariate regression analysis including above mentioned parameters revealed that significant predictors of VascAgeDiff were: weight, SBP, DBP, AoBP, CO and serum LDL cholesterol (p < 0.05).Out study suggests early vascular aging in adolescents with PH, even at mildly increased BP levels (WCH, prehypertension). Vascular changes were associated with increased weight, DBP, AoBP, CO and LDL cholesterol.

REDUCED ENDOTHELIAL GLYCOCALYX IS ASSOCIATED WITH HYPERTENSION BURDEN ONLY IN MALE SMOKERS WITH FIRST DIAGNOSED AND NEVER TREATED STAGE I AND II ESSENTIAL HYPERTENSION

Endothelial dysfunction may be estimated by reduced endothelial glycocalyx (EG). However, the role of EG as a hypertension mediated organ damage (HMOD) still remains controversial. Cigarette smoking represents a significant CV risk factor. Aim of this study is the investigation of the EG's role in first diagnosed and never treated patients with stage I and II essential hypertension regarding smoking habit.We studied 194 non-diabetic, first diagnosed and never-treated hypertensive patients (mean age=49 + 10 years, 60% males, 35% smokers). Ambulatory blood pressure monitoring (24 h ABPM) and endothelial dysfunction (PBR5-25) were estimated in each patient before treatment initiation.We found that mean 24 h systolic and diastolic ABPM levels were 140 + 8 mmHg and 87 + 9 mmHg, respectively. Regarding EG, mean values of PBR5-25, PBR5-9, PBR10-19 and PBR20-25 were 2.08 + 0.3 m, 1.16 + 0.2 m, 2.22 + 0.34 m and 2.65 + 0.8 m, respectively. No correlations were found between PBR levels and 24 h ABPM regarding the whole population. However, when we performed multiple regression analysis in a subgroup of male smoker hypertensives (n = 46, mean age=47 + 11 years), a significant association (Beta = 0.29, p = 0.05) was revealed between PBR20-25 and 24 h systolic ABPM.In first diagnosed and never treated arterial hypertension, endothelial dysfunction, represented by reduced EG, is independently related to systolic BP burden only in male smokers. Probably EG might play a significant role regarding CV risk estimation in specific groups of hypertensive patients.

OUTCOME-BASED THRESHOLD FOR CAROTID-FEMORAL PULSE WAVE VELOCITY: THE IDCARS STUDY

Guidelines recommend a > 10m/s threshold of carotid-femoral pulse wave velocity (cf-PWV) to detect hypertension mediated organ damage. However, the > 10m/s threshold was derived from the cf-PWV distribution across cross-sectional studies with limited contribution of prospective cohort studies. Using data from the International Database of Central Arterial Properties for Risk Stratification (IDCARS), we aimed to determine an outcome-based threshold for cf-PWV.Adults (> = 18 years) recruited by eight IDCARS centres and followed up for 6 months or longer qualified for inclusion in the current subject-level meta-analysis. Cf PWV was measured using the Sphygmocor device (Itasca, IL). Pulse transit distance was determined by subtracting the distance between the carotid sampling site and the suprasternal notch from the distance between the carotid and femoral sample sites. The primary endpoint consisted of fatal and nonfatal cardiovascular events. Total and cardiovascular mortality and fatal and nonfatal coronary events were secondary endpoints. The cf-PWV threshold was determined by multivariable Cox regression with average risk based on established risk factors in the whole cohort as reference.After 5.0 years of follow-up (median), of 3494 participants (mean age: 52.2 years; women: 55.3%; mean cf-PWV: 7.8 m/s), 156 (4.5%) experienced the primary endpoint, and 104 (3.0%) died, 25 (0.7%) of cardiovascular disease and 77 (2.2%) had a coronary event. After whole adjusting for sex, age, systolic blood pressure, heart rate and other cardiovascular risk factors, the outcome-driven cf-PWV thresholds were 8.6, 9.1, 8.7 and 8.6 m/s for a composite cardiovascular endpoint, all-cause and cardiovascular mortality and a coronary event, respectively. A cf-PWV > = 9 m/s (n = 752, 21.5%), compared with slower velocities, had an increased risk of a composite cardiovascular endpoint (HR: 1.75; 95% CI: 1.20-2.54, P = 0.004).The outcome-based threshold of > = 9 m/s for cf-PWV, which was present in 20% of the IDCARS participants, is close to the cut-off limit proposed by guidelines based on other approaches.

The Management of Hypertensive Emergencies-Is There a "Magical" Prescription for All?

Hypertensive emergencies (HE) represent high cardiovascular risk situations defined by a severe increase in blood pressure (BP) associated with acute, hypertension mediated organ damage (A-HMOD) to the heart, brain, retina, kidneys, and large arteries. Blood pressure values alone do not accurately predict the presence of HE; therefore, the search for A-HMOD should be the first step in the management of acute severe hypertension. A rapid therapeutic intervention is mandatory in order to limit and promote regression of end-organ damage, minimize the risk of complications, and improve patient outcomes. Drug therapy for HE, target BP, and the speed of BP decrease are all dictated by the type of A-HMOD, specific drug pharmacokinetics, adverse drug effects, and comorbidities. Therefore, a tailored approach is warranted. However, there is currently a lack of solid evidence for the appropriate treatment strategies for most HE. This article reviews current pharmacological strategies while providing a stepwise, evidence based approach for the management of HE.

Arterial Hypertension and the Hidden Disease of the Eye: Diagnostic Tools and Therapeutic Strategies.

Hypertension is a major cardiovascular risk factor that is responsible for a heavy burden of morbidity and mortality worldwide. A critical aspect of cardiovascular risk estimation in hypertensive patients depends on the assessment of hypertension-mediated organ damage (HMOD), namely the generalized structural and functional changes in major organs induced by persistently elevated blood pressure values. The vasculature of the eye shares several common structural, functional, and embryological features with that of the heart, brain, and kidney. Since retinal microcirculation offers the unique advantage of being directly accessible to non-invasive and relatively simple investigation tools, there has been considerable interest in the development and modernization of techniques that allow the assessment of the retinal vessels’ structural and functional features in health and disease. With the advent of artificial intelligence and the application of sophisticated physics technologies to human sciences, consistent steps forward have been made in the study of the ocular fundus as a privileged site for diagnostic and prognostic assessment of diverse disease conditions. In this narrative review, we will recapitulate the main ocular imaging techniques that are currently relevant from a clinical and/or research standpoint, with reference to their pathophysiological basis and their possible diagnostic and prognostic relevance. A possible non pharmacological approach to prevent the onset and progression of retinopathy in the presence of hypertension and related cardiovascular risk factors and diseases will also be discussed.

Cardiovascular Hypertension-Mediated Organ Damage in Hypertensive Urgencies and Hypertensive Outpatients.

BackgroundThe prevalence of hypertension mediated organ damage (HMOD) in patients attending the Emergency Department (ED) with symptomatic blood pressure (BP) rise is unknown, and whether HMOD varies between asymptomatic and symptomatic patients with grade 3 hypertension is unclear.AimThis study aimed to investigate cardiac and vascular HMOD in hypertensive urgencies (HU) and asymptomatic outpatients with grade 1–3 hypertension.MethodsPatients attending the ED with a symptomatic BP rise ≥180/110 mmHg were prospectively enrolled (HU group), after the exclusion of acute organ damage. HMOD and BP were assessed after 72 h from ED discharge in an office setting. These patients were matched by age and sex to outpatients with grade 3 hypertension (Grade 3 group), and by age, sex, and 72 h office BP values to outpatients with any grade hypertension (Control group).ResultsA total of 304 patients were enrolled (76 patients in the HU group, 76 in the Grade 3 group, and 152 in the Control group). Grade 3 patients had increased left ventricular mass (LVMi) compared to patients with HU (106.9 ± 31.5 vs. 96.1 ± 30.7 g/m2, p = 0.035). Severe left ventricular hypertrophy (LVH) was more frequent in grade 3 (21.1 vs. 5.3%, p = 0.004), and pulse wave velocity (PWV) was similar in the two groups. There was no difference in LVMi between ED and Control patients (96.1 ± 30.7 vs. 95.2 ± 26.6 g/m2, p = 0.807). LVH prevalence was similar (43.4 vs. 35.5%, p = 0.209, respectively), but patients with HU had thicker interventricular septum (11.9 ± 2.2 vs. 11.1 ± 2.2 mm, p = 0.007). PWV was similar between these two groups. Patients with HU needed more antihypertensive drugs than Control patients (2 vs. 1, p < 0.001).ConclusionsPatients with HU had a better cardiac HMOD profile than outpatients with grade 3 hypertension. Their cardiac and vascular HMOD is more comparable to an outpatient with similar in-office BP, although they need more antihypertensive medications.

2022 Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension.

Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Despite the positive correlations between blood pressure (BP) levels and later CV events since BP levels as low as 100/60 mmHg have been reported in numerous epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years. The publication of both the SPRINT and STEP trials (comprising > 8,500 Caucasian/African and Chinese participants, respectively) provided evidence to shake this 140/90 mmHg dogma. Another dogma regarding hypertension management is the dependence on office (or clinic) BP measurements. Although standardized office BP measurements have been widely recommended and adopted in large-scale CV outcome trials, the practice of office BP measurements has never been ideal in real-world practice. Home BP monitoring (HBPM) is easy to perform, more likely to be free of environmental and/or emotional stress, feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events, compared to routine office BP measurements. In the 2022 Taiwan Hypertension Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS), we break these two dogmas by recommending the definition of hypertension as ≥ 130/80 mmHg and a universal BP target of < 130/80 mmHg, based on standardized HBPM obtained according to the 722 protocol. The 722 protocol refers to duplicate BP readings taken per occasion ("2"), twice daily ("2"), over seven consecutive days ("7"). To facilitate implementation of the guidelines, a series of flowcharts encompassing assessment, adjustment, and HBPM-guided hypertension management are provided. Other key messages include that: 1) lifestyle modification, summarized as the mnemonic S-ABCDE, should be applied to people with elevated BP and hypertensive patients to reduce life-time BP burden; 2) all 5 major antihypertensive drugs (angiotensin-converting enzyme inhibitors [A], angiotensin receptor blockers [A], β-blockers [B], calcium-channel blockers [C], and thiazide diuretics [D]) are recommended as first-line antihypertensive drugs; 3) initial combination therapy, preferably in a single-pill combination, is recommended for patients with BP ≥ 20/10 mmHg above targets; 4) a target hierarchy (HBPM-HMOD- ambulatory BP monitoring [ABPM]) should be considered to optimize hypertension management, which indicates reaching the HBPM target first and then keeping HMOD stable or regressed, otherwise ABPM can be arranged to guide treatment adjustment; and 5) renal denervation can be considered as an alternative BP-lowering strategy after careful clinical and imaging evaluation.

Utility of ambulatory blood pressure monitoring in detection of masked hypertension and risk of hypertension mediated organ damage in normotensive patients with type 2 diabetes mellitus

Purpose In patients with diabetes, unrecognised hypertension is a serious problem risk factor for the development and progression of chronic complications. The study aimed to determine the prevalence of masked hypertension in normotensive diabetic patients, the factors affecting it, and its association with diabetes complications using ambulatory blood pressure monitoring (ABPM). Materials and methods A cross-sectional observational study was conducted on 150 normotensive diabetic patients. Patients were subjected to an interview and clinical examination to record demographic data, epidemiological data, and significant past history. ABPM was performed for each patient. Urine samples, echocardiogram, and ophthalmologic fundoscopy were done to check for diabetes-related complications. Results The mean age of all participants was 56.7 ± 7.8 years. A total of 93 patients (62%) were males. 99 (66%) patients had masked hypertension. A total of 85 (56.7%) were non-dippers, 49 (32.7%) were dippers, 1 (0.7%) was extreme dipper and 15 (10%) were reverse dippers. Non-dipping and reverse dipping were associated with concentric left ventricular hypertrophy LVH (p < .001). Masked hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.008) whereas, nocturnal hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.003). Conclusions A single office blood pressure (BP) reading cannot rule out hypertension in patients with diabetes. Regardless of hypertension, clinicians should have all patients, especially patients with diabetes, undergo ABPM at least once. Masked hypertension, changes in nocturnal dipping and other phenomena that raise the risk of diabetes complications but cannot be measured by office BP can be measured by ABPM, and thus ABPM can provide a good prognostic benefit.

A pilot study to evaluate the erythrocyte glycocalyx sensitivity to sodium as a marker for cellular salt sensitivity in hypertension

Supressed plasma renin in patients with primary hypertension is thought to be an indirect marker of sodium-induced volume expansion which is associated with more severe hypertension and hypertension-mediated organ damage. A novel test for erythrocyte glycocalyx sensitivity to sodium (eGCSS) has been proposed as a direct measure of sodium-induced damage on erythrocyte surfaces and a marker of sensitivity of the endothelium to salt in humans. Here we explore if eGCSS relates to plasma renin and other clinical and biochemical characteristics in a cohort of patients with primary hypertension. Hypertensive subjects (n = 85, 54% male) were characterised by blood biochemistry (including plasma renin/aldosterone), urine analysis for albumin-creatinine ratio (ACR), 24-h urine sodium/potassium excretion. eGCSS was measured using a commercially available kit. Correlations between eGCSS and clinical and biochemical characteristics were explored using Spearman’s correlation coefficient and characteristics compared across tertiles of eGCSS. eGCSS was inversely correlated with renin (p < 0.05), with renin 17.72 ± 18 µU/l in the highest tertile of eGCSS compared to 84.27 ± 146.5 µU/l in the lowest (p = 0.012). eGCSS was positively correlated with ACR (p < 0.01), with ACR 7.37 ± 15.29 vs. 1.25 ± 1.52 g/mol for the highest vs. lowest tertiles of eGCSS (p < 0.05). eGCSS was not correlated with other clinical characteristics or biochemical measures. These results suggests that sodium retention in hypertension characterised by a low-renin state is associated with cell membrane damage reflected by eGCSS. This may contribute to the hypertension-mediated organ damage and the excess mortality associated with sodium overload and “salt sensitivity”.

Hypertension mediated organ damage in children and adolescents

Hypertension mediated organ damage in children and adolescents

Impact of underweight on 3-year all-cause mortality in patients with acute severe hypertension: a retrospective cohort study

Body mass index (BMI) is used to measure body fat. We investigated the association between BMI and long-term clinical outcomes in patients with acute severe hypertension who visited the emergency department (ED). Cross-sectional study data were obtained from a single regional emergency medical center, including patients with elevated initial systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg. The patients were classified into five groups according to BMI level (underweight, normal, overweight, obese class I, II and III). Among 4867 patients who presented with acute severe hypertension at the ED, 935 (19.21%) died within 3-years. In particular, 140 (44.59%) patients in the underweight group died from any cause, which was the highest among the five groups, and there was a reverse J-shaped association between BMI and 3-year all-cause mortality. Underweight patients had a significantly increased risk of all-cause mortality by 1.55-fold during the 3-year follow-up. Rather, obesity was associated with a reduction in the 3-year all-cause mortality. Comorbidities, including chronic kidney disease and acute hypertension-mediated organ damage, were independent predictors of all-cause mortality in patients who were not underweight. Underweight contributes to worsening long-term clinical outcomes in patients with acute severe hypertension. Clinicians should consider BMI as one of the physical examination parameters in patients with acute severe hypertension, and management including lifestyle modifications such as diet control and exercise should be undertaken considering BMI and comorbidities.

Modulating the immune response to reduce hypertension-associated cardiovascular damage

Cardiovascular diseases are a leading cause of mortality and disability worldwide. Hypertension, a major risk factor for these diseases, remains difficult to treat despite numerous drugs being available. In this issue of the JCI, Failer et al. show that the endogenous antiinflammatory agent developmental endothelial locus-1 (DEL-1) decreased blood pressure and cardiac and aortic hypertrophy in mouse models of hypertension through reduction in αvβ3 integrin–dependent metalloproteinase activity and immune cell recruitment, leading to reduced production of proinflammatory cytokines in cardiovascular tissues. This study offers an alternative in the treatment of hypertension-mediated organ damage through the immunomodulatory effect of DEL-1.