Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

Relationship of a Body Shape Index and Body Roundness Index with carotid atherosclerosis in arterial hypertension.

BACKGROUND AND AIMS: A Body Shape Index (ABSI) and Body Roundness Index (BRI) are two new anthropometric adiposity indices that have shown to be associated better than BMI with adipose abdominal tissue, with the onset of diabetes and the risk of premature death. Little is known about the influence of ABSI and BRI on subclinical vascular damage. The study was aimed to assess the relationship between ABSI and BRI with carotid atherosclerosis damage in subjects with arterial hypertension. METHODS AND RESULTS: A total of 468 patients with arterial hypertension (30-80 years old) were enrolled; adiposity indices were calculated (BMI, WC, ABSI, BRI) and carotid ultrasonographic examination was performed to detect atherosclerotic damage (IMT or atherosclerotic plaque). BRI, but not ABSI, was higher in subjects with IMT> 0.90 mm in comparison to those with a lower IMT (p < 0.001), whereas patients with carotid plaques showed higher values of ABSI (p = 0.001), as well as of BRI (p = 0.003). Linear regression analysis disclosed significant correlation of IMT with ABSI, BRI and BMI (all p < 0.001). In the multivariate analysis, BRI was independently correlated with cIMT (p = 0.015). On the contrary, ABSI did not show any independent association with cIMT. However, ABSI was strongly associated with carotid plaques in multiple logistic regression analysis after adjustment for potential confounding factors. When BRI or BMI replaced ABSI into the multivariate models, they did not show any independent correlation with carotid plaques. CONCLUSIONS: ABSI may be proposed as a better correlate of carotid atherosclerosis than the traditional measures of adiposity.

The Relationship Between Aortic Root Size and Hypertension: An Unsolved Conundrum.

Thoracic aortic aneurysms rupture and dissection are among the most devastating vascular diseases, being characterized by elevated mortality, despite improvements in diagnostic imaging and surgical techniques.An increased aortic root diameter (ARD) represents the main risk factor for thoracic aortic dissection and rupture and for aortic valve regurgitation.Even though arterial hypertension is commonly regarded as a predisposing condition for the development of thoracic aorta aneurysms, the role of blood pressure (BP) as determinant of aortic root enlargement is still controversial. The use of different methods for indexation of ARD may have in part contributed to the heterogeneous findings obtained in the investigations exploring the relationships between ARD and BP. Indeed, the best methods for ARD indexation, as well as the normal values of aortic root size, are still a matter of debate.Several non-hemodynamic factors influence ARD, including age, gender, and anthropometric variables, such as height, weight and their derivatives body surface area (BSA) and body mass index. Of these factors, anthropometric variables have the greatest impact.Several studies documented an association between ARD enlargement, assessed by echocardiography, and some indices of hypertensive target organ damage such as left ventricular hypertrophy, diastolic dysfunction, and carotid intima-media thickening. Recently, we found that ARD, expressed either as absolute values or normalized for BSA (ARD/BSA) or height (ARD/H), was significantly greater in hypertensive subjects with chronic kidney disease (CKD) when compared to their counterparts with normal renal function. Moreover, at univariate analyses estimated glomerular filtration rate (eGFR) showed significant inverse correlations with ARD not indexed and with ARD/BSA and ARD/H. Taking into account the effect of age, sex, duration of hypertension and other potentially confounding factors, in multiple regression analyses, only the association of GFR with ARD/H and that between GFR and ARD/BSA remained statistically significant. The receiver-operating characteristic curve analysis revealed that an estimated GFR of about 50 ml/min/1.73 m2 represents the better threshold to distinguish hypertensive patients with dilated aortic root from those with a normal one.Some population-based studies showed that an enlarged ARD might predict an adverse prognosis, even in absence of aneurysmatic alterations.In the Cardiovascular Health Study, a dilated aortic root was independently associated with an increased risk for stroke, cardiovascular and total mortality in both sexes and with incident congestive heart failure only in men. The relationship between ARD and heart failure has been observed also in the Framingham Heart Study. More recently, the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study demonstrated an independent relationship of ARD/H with incident cardiovascular morbidity and mortality.Although the relationship between BP and aortic root size is still a matter of debate, increasing evidence seems to support the notion that aortic root dilatation, even in absence of aneurysmatic alterations, may be regarded as an hypertensive organ damage paralleling other preclinical markers whose unfavourable prognostic significance is firmly established. Future studies are needed to assess whether or not antihypertensive therapy is able to reduce aortic root dimension and the increased risk associated with its enlargement.

Subclinical Kidney Damage in Hypertensive Patients: A Renal Window Opened on the Cardiovascular System. Focus on Microalbuminuria.

The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30 mL/min/1.73 m2 and 60 mL/min/1.73 m2 or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30-300 mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30-300 mg/g.There is clear evidence that urinary albumin excretion levels, even below the cut-off values used to define MAU, are associated with an increased risk of CV events. The relationships of MAU with a variety of risk factors, such as blood pressure, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced CV risk conferred by MAU. Nonetheless, several studies showed that the association between MAU and CV disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between MAU and CV risk remain to be elucidated. The simple search for MAU and in general of subclinical renal involvement in hypertensive patients may enable the clinician to better assess absolute CV risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard CV risk factors.

May Measure Month 2022 in Italy: A Focus on Fixed-dose Combination, Therapeutic Adherence, and Medical Inertia in a Nationwide Survey.

INTRODUCTION: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. METHODS: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. RESULTS: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). CONCLUSIONS: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD).

Chronic kidney disease (CKD) is characterized by an increased risk of kidney failure and end-stage renal disease (ESRD). Aging and comorbidities as cardiovascular diseases, metabolic disorders, infectious diseases, or tumors, might increase the risk of dialysis. In addition, genetic susceptibility factors might modulate kidney damage evolution. We have analyzed, in a group of ESRD patients and matched controls, a set of SNPs of genes (Klotho rs577912, rs564481, rs9536314; FGF23 rs7955866; IGF1 rs35767; TNFA rs1800629; IL6 rs1800795; MIF rs755622, rs1007888) chosen in relation to their possible involvement with renal disease and concomitant pathologies. Analysis of the raw data did indicate that IL6 rs180795 and MIF rs755622 SNPs might be markers of genetic susceptibility to ESRD. In particular, the C positive genotypes of MIF rs755622, (dominant model) seem to be an independent risk factor for ESDR patients (data adjusted for age, gender, and associated pathologies). Stratifying results according to age MIF rs755622 C positive genotype frequencies are increased in both the two age classes considered (<59 and ≥59-year-old subjects). Analyses of data according to gender allowed us to observe that ESRD women shoved a significantly reduced frequency of genotypes bearing IL6 rs180795 C allele. In addition, MIF rs755622 might interact with diabetes or hypercholesterolemia in increasing susceptibility to ESRD. In conclusion, our data indicate that some polymorphisms involved in the regulation of both renal function and inflammatory response can influence the evolution of chronic kidney disease and suggest that the modulation of the activities of these and other genes should also be considered as therapeutic targets on to intervene with innovative therapies.

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.

Should reduction of increased short-term blood pressure variability be a target of antihypertensive therapy?

It has long been known that blood pressure (BP) is characterized by marked short-term fluctuations occurring within a 24-h period and also by long-term oscillations occurring over more prolonged periods of time. An increased short-term blood pressure variability (BPV) appears to importantly contribute to target organ damage and to the enhanced cardiovascular risk of hypertensive patients, over and above the effect of an increase in mean BP levels. Reducing 24-h mean BP is the main aim of antihypertensive therapy, but initial data are available that additional cardiovascular protection can be achieved by reducing BPV. However, to definitively prove the prognostic role of short-term BPV and the need for its control by treatment, evidence is still needed from intervention trials aimed at demonstrating that by reducing BPV through administration of antihypertensive drugs, a reduction in organ damage and in the rate of cardiovascular events can be obtained.

Resistive index of ophthalmic artery as an imaging biomarker of hypertension-related vascular and kidney damage.

Aim: Resistive index of ophthalmic artery (RI-OA) is associated with atherosclerotic diseases. The aim of this study was to evaluate the association of RI-OA and hypertension-related vascular and kidney damage. Materials and methods: Two-hundred and eighty hypertensive patients underwent evaluation of RI-OA, carotid atherosclerosis and level of 24 h albuminuria. Results: Albuminuria and carotid atherosclerosis were positively associated with RI-OA independently of other cardiovascular risk factors. Receiver-operating characteristic curve analysis allowed us to calculate a cut-off value of RI-OA >0.625, which would be suspicious about the existence of atherosclerotic disease. Conclusion: The ophthalmic vascular circulation allows to study connections between macro- and microcirculation in vivo. RI-OA could be a useful marker for a better stratification of the risk of developing kidney and cardiovascular disease.

Relationship of choroidal thickness with pulsatile hemodynamics in essential hypertensive patients.

Controversy exists about the association of choroidal thickness (CTh) with blood pressure (BP) values. There is some evidence suggesting that central hemodynamics changes are associated with microvascular disease. Our study was aimed to assess the relationships between CTh and clinic and 24-h BP and between CTh and estimated 24-h aortic pulse pressure (aPP), 24-h aortic systolic BP (aSBP), and 24-h aortic augmentation index (aAIx) in a group of hypertensive patients. We enrolled 158 hypertensive subjects (mean age 48 ± 13 years) all of which underwent evaluation of the choroidal district by Swept-Source optical coherence tomography (SS-OCT) and 24-h BP monitoring, in order to measure peripheral BP and to estimate central hemodynamic parameters. Inverse significant correlations of clinic PP, 24-h aPP, 24-h aSBP, and 24-h aAIx with thicknesses of central ring, inner ring, and outer ring of the choroid and its overall average were found. The strongest of these correlations was that relating 24-h aPP with overall average choroidal thickness (r = -.531; P < .001). When we divided the study population in subjects with 24-h aPP above and below the median value (35 mm Hg), CTh were thinner in subjects with higher values of 24-aPP as compared to those with lower ones, even after adjustment for age, and other potential confounders. The relationships of CTh with 24-h aPP remained significant also taking into account the effects of various covariates in linear multiple regression analyses. Our findings support the concept of a cross-talk between macro- and microcirculation.

Relationship of fetuin-A with glomerular filtration rate and endothelial dysfunction in moderate-severe chronic kidney disease.

BACKGROUND: In end-stage renal disease, fetuin-A has been demonstrated to be reduced and inversely related to cardiovascular mortality. This study had 2 distinct aims. The first was to verify if circulating concentration of fetuin-A may depend on renal function in patients with chronic kidney disease (CKD). Furthermore, we analyzed the correlation of fetuin-A with the biomarker of endothelial dysfunction endothelin-1 (ET-1), and with the inflammatory cytokine interleukin-6 (IL-6). METHODS: In 108 subjects with stage 3-5 CKD, plasma levels of fetuin-A, ET-1 and IL-6 were assayed. Patients were studied first as a whole group and then were divided according to stages of CKD and fetuin-A tertiles. RESULTS: Fetuin-A concentration decreased in parallel with the increase in ET-1 and IL-6 levels as renal function declined. Multiple regression analysis showed that fetuin-A was independently associated with estimated glomerular filtration rate (beta=0.386; p<0.001), IL-6 (beta=-0.393; p=0.001) and ET-1 (beta=-0.219; p=0.02), in a multivariate model including also sex, parathyroid hormone and the calcium x phosphorus product. CONCLUSIONS: These results seem to indicate that in CKD, even when not severe, inflammatory processes are increased and linked to endothelial dysfunction, worsening progressively with the decline of renal function.

Left ventricular mass in hypertensive patients with mild-to-moderate reduction of renal function.

AIM: Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular (CV) morbidity and mortality. The aim of the present study was to evaluate the relationship between LV mass and mild-to-moderate renal dysfunction in a group of non-diabetic hypertensives, free of CV diseases, participating in the Renal Dysfunction in Hypertension (REDHY) study. METHODS: Patients with diabetes, a body mass index (BMI) of more than 35 kg/m(2), secondary hypertension, CV diseases and a glomerular filtration rate (GFR) of less than 30 mL/min per 1.73 m(2) were excluded. The final sample included 455 patients, who underwent echocardiographic examination and ambulatory blood pressure monitoring. RESULTS: There was a significant trend for a stepwise increase in LV mass, indexed by both body surface area (LVMI) and height elevated to 2.7 (LVMH(2.7)), with the declining renal function, that remained statistically significant after correction for potential confounders. The prevalence of LVH, defined either as LVMI of 125 g/m(2) or more or as LVMH(2.7) of 51 g/m(2.7) or more, was higher in subjects with lower values of GFR than in those with normal renal function (P < 0.001 in both cases). The multiple regression analysis confirmed that the inverse association between GFR and LVM was independent of confounding factors. CONCLUSION: The present study confirms the high prevalence of LVH in patients with mild or moderate renal dysfunction. In the patients studied (all with a GFR of 30 mL/min per 1.73 m(2)), the association between LVM and GFR was independent of potential confounders, including 24 h blood pressure load. Taking into account the negative prognostic impact of LVH, further studies focusing on a deeper comprehension of the mechanisms underlying the development of LVH in chronic kidney disease patients are needed.

Choroidal thickness is associated with renal hemodynamics in essential hypertension.

The choroid is the most vascularized structure of the eye and plays a central role in the development of the retinal vascular changes that occur in arterial hypertension. Changes of choroidal thickness (ChT) assessed by optical coherence tomography (OCT) technology could reflect the vascular complications of hypertension. Also, intrarenal hemodynamic damage, associated with endothelial dysfunction, demonstrated to be a good indicator of systemic morphofunctional arterial impairment. The aim of this study is to assess the relationship between ChT and renal hemodynamics in subjects with essential hypertension. Routine laboratory tests, clinical history, and physical examination, including blood pressure assessment, were performed in 90 subjects with essential hypertension. All patients underwent Doppler ultrasonographic evaluation of intra-renal hemodynamics and OCT imaging to assess ChT. When subjects were divided in two groups based on renal resistive index (RRI), group I (RRI ≥ 75% percentile) showed significantly lower values of ChT than group II (RRI < 75% percentile) (P < .001). When divided in two groups based on the ChT median values, patients with lower ChT had significantly higher RRI values than those with ChT above the median values (P < .05). In multivariate model including age, eGFR, and other variables as confounding factors, RRI ≥ 75% was independently associated with ChT. ChT was significantly correlated with renal resistive index in subjects with essential hypertension, confirmed in multivariate analyses. This result could be referred to changes in vascular elastic properties that occur in retinal and intrarenal vascular system probably due to oxidative stress and endothelial dysfunction commonly found in early complications of hypertension.

Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients.

BACKGROUND: Hypertension and additional non-traditional risk factors can damage the kidney directly and by promoting atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate a large part of the effects of risk factors on the kidney. We hypothesized that in hypertensive patients (HT), oxidative stress, measured as 8-ISO-prostaglandin F2alpha (8-ISO-PGF2alpha), should raise paralleling decreasing renal function and should correlate with estimated glomerular filtration rate (eGFR). METHODS: In 626 HT with renal function ranging from stages 1 to 5 and 100 healthy controls, plasma levels of 8-ISO-PGF2alpha, high-sensitivity C-reactive protein (CRP), transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) were measured. GFR was estimated by the Modification of Diet in Renal Disease study equation. RESULTS: When HT were stratified according to renal function stages, 8-ISO-PGF2alpha, CRP, TGF-beta and ET-1 increased progressively and significantly with decreasing eGFR. The multiple regression analysis, considering eGFR as a dependent variable, showed that 8-ISO-PGF2alpha (beta = -0.361, P < 0.000001), ET-1 (beta = -0.197, P < 0.0001) and TGF-beta (beta = -0.170, P < 0.0004) correlated independently with eGFR. All biomarkers were good predictors of eGFR <60 ml/min/1.73 m(2) [receiver-operator-curve (ROC) areas]. ET-1 was shown to be the best predictor with a ROC area = 0.938; with a threshold of 4 pg/ml, 91% sensitivity and 85% specificity were observed, whereas 8-ISO had a ROC area = 0.931, and for a threshold of 329 pg/ml, sensitivity and specificity were 89%, respectively. In contrast, CRP showed the lower predictive value with a ROC area = 0.917; with a threshold of 2.52 mg/l, an 87% sensitivity and an 83% specificity were obtained. CONCLUSIONS: Our findings are a clear-cut demonstration of a strong and negative correlation of both oxidative stress and ET-1 with renal function stages in HT. ET-1 and 8-isoprostane are predictive of eGFR.

The Unsolved Conundrum of Optimal Blood Pressure Target During Acute Haemorrhagic Stroke: A Comprehensive Analysis.

Intracerebral haemorrhage (ICH) is a devastating cerebrovascular disease, which accounts to 15% of all strokes. Among modifiable risk factors for ICH, hypertension is the most frequent. High blood pressure (BP) is detected in more than 75-80% of patients with ICH. Extremely elevated BP has been associated with early hematoma growth, a relatively frequent occurrence and powerful predictor of poor outcome in patients with spontaneous ICH. On the other hand, excessively low BP might cause cerebral hypoperfusion and ultimately lead to poor outcome. This review will analyse the most important trials that have tried to establish how far should BP be lowered during acute ICH. These trials have demonstrated either a small non-significant benefit (INTERACT-2, INTEnsive blood pressure Reduction in Acute Cerebral haemorrhage Trial) or no benefit (ATACH-2, Antihypertensive treatment of acute cerebral haemorrhage II study) when intensive systolic BP reduction was compared with modest or standard BP reduction. The more recent meta-analyses including studies investigating this issue yielded similar conclusions: aggressive BP control in the acute phase of ICH is not beneficial. For these reasons the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the management of arterial hypertension, do not recommend treatment to immediately lower BP in patients with acute ICH and systolic BP < 220 mmHg. Careful lowering of SBP to less than 180 mmHg via i.v. Infusion may be considered only in patients with SBP ≥ 220 mmHg.

Association between early-stage chronic kidney disease and reduced choroidal thickness in essential hypertensive patients.

The introduction in the past few years of advanced optical coherence tomography (OCT) techniques has greatly increased our understanding of the choroid, which is the most important vascular layer of the eye. Our study aimed to assess choroidal thickness by using swept-source OCT (SS-OCT) in essential hypertensive patients (EHs) with and without early-stage chronic kidney disease (CKD). We enrolled 100 EHs, of whom 65 were without kidney damage, and 35 had stage 1-3 CKD. In all of the participants, SS-OCT and a routine biochemical workup were performed. Glomerular filtration rate (GFR) was estimated by the CKD Epidemiology Collaboration equation (eGFR). CKD was defined in agreement with the Kidney Disease Outcomes Quality Initiative Kidney Disease: Improving Global Outcomes 2002 guidelines. OCT measurements were performed according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, which divides the macula into nine subfields. The circular grid consists of three concentric rings. EHs with CKD showed thinner choroidal thicknesses than those without it (all p < 0.05), even after adjustment for potential confounding factors. Overall choroidal thickness correlated significantly and directly with eGFR (r = 0.36) and negatively with urinary albumin excretion (r = -0.39). The association of choroidal thickness with CKD was confirmed in multiple logistic regression analyses once the effects of age and other confounding variables were accounted for. The odds ratio of having early-stage CKD associated with a standard deviation increase in overall choroidal thickness was 0.43 (0.24-0.75, 95% confidence interval; p = 0.007). In conclusion, our study confirms the close relationships between changes in ocular microcirculation and renal dysfunction.

Inflammation and Aortic Pulse Wave Velocity: A Multicenter Longitudinal Study in Patients With Inflammatory Bowel Disease.

Background Inflammatory bowel disease ( IBD ) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse-wave velocity ( aPWV ), and an excess of cardiovascular events. We have previously hypothesized that the cardiovascular risk excess reported in these patients could be explained by chronic inflammation. Here, we tested the hypothesis that chronic inflammation is responsible for the increased aPWV previously reported in IBD patients and that anti-TNFa (anti-tumor necrosis factor-alpha) therapy reduce aPWV in these patients. Methods and Results This was a multicenter longitudinal study. We enrolled 334 patients: 82 patients with ulcerative colitis, 85 patients with Crohn disease, and 167 healthy control subjects matched for age, sex, and mean blood pressure, from 3 centers in Europe, and followed them for 4 years (range, 2.5-5.7 years). At baseline, IBD patients had higher aPWV than controls. IBD patients in remission and those treated with anti-TNFa during follow-up experienced an aortic destiffening, whereas aPWV increased in those with active disease and those treated with salicylates ( P=0.01). Disease duration ( P=0.02) was associated with aortic stiffening as was, in patients with ulcerative colitis, high-sensitivity C-reactive protein during follow-up ( P=0.02). All these results were confirmed after adjustment for major confounders. Finally, the duration of anti-TNFa therapy was not associated with the magnitude of the reduction in aPWV at the end of follow-up ( P=0.85). Conclusions Long-term anti-TNFa therapy reduces aPWV , an established surrogate measure of cardiovascular risk, in patients with IBD . This suggests that effective control of inflammation may reduce cardiovascular risk in these patients.

Renal haemodynamics and coronary atherosclerotic burden are associated in patients with hypertension and mild coronary artery disease.

Intrarenal hemodynamic alterations are independent predictors of cardiovascular events in different populations. It has been hypothesized that there is an association between renal hemodynamics and coronary atherosclerotic burden in patients with hypertension. Therefore, the present study examined the associations between renal hemodynamics, coronary atherosclerotic burden and carotid atherosclerotic disease. A total of 130 patients with hypertension aged between 30-80 years who had been referred for an elective coronary angiography were enrolled in the present study. A duplex ultrasound of the intrarenal vasculature was performed to evaluate the resistive index (RI), pulsatility index (PI) and acceleration time (AT). The carotid intima-media thickness was additionally assessed. A coronary angiography was performed to detect the atherosclerotic burden using the Gensini Score (GS). Based on the GS values, subjects were divided into quintiles (I: ≤9; II: 9-17; III: 17-30; IV: 30-44; and V: GS >44) as well as in subjects with mild (GS ≤30) or severe coronary disease (GS >30). A weak significant difference in PI was identified among quintiles (P=0.041), whereas, RI and AT did not differ significantly. PI was associated with GS in the group with low coronary atherosclerotic burden (GS ≤30; P=0.047), whereas, no association was detected in subjects with GS >30. This association remained following adjustment for age and left ventricular ejection fraction (P=0.025). In conclusion, renal vascular alterations were associated with coronary atherosclerotic burden in patients with hypertension with mild coronary disease.

Plasma aldosterone and its relationships with left ventricular mass in essential hypertensive patients with the metabolic syndrome.

BACKGROUND: The association of aldosterone with the metabolic syndrome (MetS) has not been fully elucidated. The aim of our study was to evaluate the relationships of plasma aldosterone concentration (PAC) with MetS and left ventricular mass (LVM) in nondiabetic Caucasian patients with essential hypertension. METHODS: Measurements were taken with the patients off antihypertensive medications. The measurements included 24-h blood pressure (BP) readings, plasma renin activity (PRA) and aldosterone, and an echocardiogram. RESULTS: Subjects with MetS (n = 201) had higher age-adjusted PAC (10.2 +/- 5.8 vs. 11.6 +/- 5.9 ng/dl; P = 0.01) and greater age-adjusted LVM indexed for height2.7 (LVMH2.7) (56 +/- 19 vs. 62 +/- 20 g/m2; P = 0.001) than those without MetS (n = 249). The difference in respect of PAC between the two groups was independent of PRA and was attributable mainly to obesity. After adjusting for potential confounders, LVMH2.7 was associated with MetS as a whole (beta = 0.11; P = 0.02) and with body mass index (BMI) (beta = 0.19; P < 0.0001) in the overall population. The latter relationship was attenuated (beta = 0.15; P = 0.001) after further adjustment for PAC. In the MetS group the association of LVMH2.7 with PAC held (beta = 0.19; P = 0.007) in multivariate analyses. In subjects without MetS, this relationship had only borderline statistical significance. CONCLUSIONS: Our results suggest that the elevated PAC related to obesity may help to explain the increased LVM observed in association with MetS, and may contribute to enhancing the cardiovascular risk associated with MetS.