OBJECTIVE:Malignant hypertension (MH) remains a life-threatening condition and new pharmacological strategies and drugs with potential new mode of actions are currently investigated. The aim of the present study was to evaluate the effects of nitric oxide (NO)-independent soluble guanylyl cyclase (sGC) stimulator on the long-term MH-related mortality and morbidity. METHODS:As a model of MH, Ren-2 transgenic rats (TGR) treated with nonspecific NO synthase inhibitor, [Nω-nitro-l-arginine methyl ester - (L-NAME)], was used. Systolic blood pressure (SBP) was measured by tail-cuff method. The treatment with sGC stimulator, BAY41-8543, was started 3 days before administration of L-NAME. The follow-up period was 120days after L-NAME administration. RESULTS:Untreated TGR + L-NAME rats developed MH (SBP on day +10 was 207 ± 4 mmHg) associated with development of marked albuminuria and high mortality (median survival rate 8 days). The treatment with sGC stimulator BAY41-8543 completely abolished MH-related mortality in TGR receiving L-NAME (all animals survived until end of the study) and prevented rises in SBP and development of albuminuria. CONCLUSION:The treatment with sGC stimulator BAY41-8543 provided long-term protection against MH-related mortality and morbidity. On the whole, these results suggest that pharmacological targeting NO/sGC pathway should be considered in attempts to develop new pharmacological strategies for treatment of MH.
OBJECTIVES:Periodontitis may promote chronic systemic inflammation leading to elevation of blood pressure (BP) and arterial stiffening. We explored sex-specific associations of periodontitis severity and inflammation with BP and arterial stiffness. METHODS:BP and arterial stiffness by carotid-femoral pulse wave velocity (cf-PWV) were measured in 673 women and 565 men, mean age 68 years. Periodontitis was staged using the European Federation of Periodontology/American Academy of Periodontology 2018 classification. Periodontal inflammation was assessed by full-mouth registration of bleeding on probing (BoP) and number of sites with combined probing pocket-depth (PPD) ≥ 4 mm and BoP. The associations of periodontitis severity and periodontal inflammation with BP and arterial stiffness were tested in sex-specific linear/logistic regression analyses, adjusted for diabetes, smoking, BMI, education, and antihypertensive treatment. RESULTS:Men had higher BP and cf-PWV than women (both P < 0.01). Stage II (moderate) and III/IV (advanced) periodontitis were found in 24 and 76% of women and 18 and 82% of men (P = 0.03). Mean BoP was 55 in both genders (P = 0.91). In adjusted analysis, stage III/IV (advanced) periodontitis was associated with higher SBP and DBP in women only (β = 0.08 and β = 0.09, both P < 0.05). BoP was associated with higher DBP only in women (β = 0.12) (P for sex interaction < 0.05) and with higher cf-PWV in men (β = 0.09) (both P < 0.05). PPD ≥ 4 mm with BoP was associated with increased arterial stiffness in women (P = 0.03). CONCLUSION:Advanced periodontitis and periodontal inflammation were both associated with higher BP only in women, while periodontal inflammation was associated with increased arterial stiffness in both genders.
Primary aldosteronism is an underdiagnosed and potentially treatable cause of secondary hypertension. We evaluated the incidence of clinically recognized primary aldosteronism among adults with clinically coded hypertension receiving intensive multidrug antihypertensive therapy in the TriNetX Analytics Network from 2010 through 2024. Among 1 888 042 eligible adults without prior primary aldosteronism, 1528 incident diagnoses were identified, corresponding to an incidence proportion of 0.081%, or 0.81 cases per 1000 patients. Diagnostic recognition varied by demographic subgroup and was highest among younger adults, males, Black or African American individuals, and Hispanic or Latino individuals. These findings suggest that documented recognition of primary aldosteronism in routine clinical practice remains low even among patients receiving intensive antihypertensive therapy. Because diagnoses were identified using electronic health record coding rather than systematic biochemical testing, results should be interpreted as clinical recognition rather than true disease prevalence.
OBJECTIVE:The efficacy of adrenalectomy compared to the efficacy of treatment with esaxerenone in improving vascular function and arterial stiffness in patients with aldosterone-producing adenoma (APA) remains uncertain. The aim of this study was to determine the effects of esaxerenone on blood pressure, serum potassium, vascular function and arterial stiffness in patients with APA and to compare the effects of adrenalectomy and treatment with esaxerenone on vascular function and arterial stiffness as surrogate markers of cardiovascular events. METHODS:Flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), and brachial-ankle pulse wave velocity (baPWV) were measured to assess vascular function and arterial stiffness before and after 3-month treatment with esaxerenone and at 3 months after adrenalectomy in 20 patients with APA. RESULTS:FMD, NID, and baPWV after treatment with esaxerenone were significantly better than those before treatment with esaxerenone. FMD, NID, and baPWV after adrenalectomy were significantly better than those before treatment with esaxerenone. NID after adrenalectomy was significantly higher than that after treatment with esaxerenone (14.9 ± 4.8% vs. 13.0 ± 4.6%, P = 0.03). The changes in FMD, NID, and baPWV after adrenalectomy were significantly correlated with the changes in plasma aldosterone concentration. CONCLUSIONS:Compared with esaxerenone treatment, adrenalectomy provided more favorable improvements in vascular function and arterial stiffness in patients with APA. Nevertheless, esaxerenone also improved blood pressure, serum potassium levels, vascular function, and arterial stiffness, suggesting that it may be a beneficial treatment option for patients with APA who are inoperable or refuse surgery.
BACKGROUND:High blood pressure (BP) is the leading modifiable risk factor for cardiovascular disease (CVD) and mortality. The prognostic relevance of invasive central versus peripheral BP for predicting major adverse CVD events (MACEs) remains unexplored. This exploratory study examined the prognostic associations of invasive central and peripheral BP measurement in a cohort of older patients with higher CVD risk. METHODS:In 238 patients undergoing elective coronary angiography (mean age 69 ± 11 years, 72% males), invasive aortic and brachial BP were measured sequentially. Patients were followed for 37 ± 23 months for MACEs, defined as a composite of CVD death, nonfatal myocardial infarction or stroke, hospitalization for unstable angina or heart failure. RESULTS:Both aortic and brachial invasive pulse pressures (PP) were independently associated with MACEs [adjusted hazard ratio (aHR) per 10 mmHg increase 1.11, 95% CI 1.01-1.22, P = 0.03, and 1.10, 95% CI 1.01-1.21, P = 0.04, respectively]. Associations of aortic [aHR 1.08, 95% CI 0.99-1.17, P = 0.07] and brachial (aHR 1.07, 95% CI 0.98-1.17, P = 0.13] systolic BPs were borderline. Differences in receiver operating characteristic performance between aortic and brachial PPs (area under the curve difference = 0.02) were not significant. Optimal thresholds for brachial PP to predict MACEs were 10 mmHg higher than aortic PP. CONCLUSIONS:In this exploratory cohort of older, higher-risk patients, invasive aortic and brachial PPs showed broadly similar associations with MACEs. Although numerically different, aortic PP appears to offer negligible incremental prognostic value beyond brachial PP, suggesting that measurement at either site would be clinically valuable. These findings warrant confirmation in adequately powered studies.
GRAPHICAL ABSTRACT:https://links.lww.com/HJH/D83.
Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal and perinatal morbidity and mortality worldwide, especially in low- and middle-income countries. Moreover, HDP are directly linked to an increased risk of long-term cardiometabolic and kidney disease in mothers and offspring. Since prevention, diagnosis, and treatment of HDP remain suboptimal globally, enhanced understanding and implementation of current guidelines on HDP present a substantial opportunity to significantly reduce maternal and fetal morbidity and mortality. This position paper by the International Society of Hypertension reviews current knowledge in the field, identifies knowledge gaps and provides recommendations on the care of women with HDP and lifelong care, thereafter.
OBJECTIVE:Foam rolling reduces vascular resistance and enhances peripheral blood flow; however, its ability to attenuate pressure wave reflection remains purely hypothetical. Given the positive correlation between skeletal muscle mass and flow-mediated vasodilation, the present study investigated the acute effects of foam rolling on pressure wave reflection and explored whether skeletal muscle index moderates this response. METHODS:Twenty-six men and women (age, 22-62 years) completed 20 min of foam rolling and sham control on separate days in a randomized controlled crossover design. Skeletal muscle index was calculated as skeletal muscle mass/height2 (bioelectrical impedance analysis), and the BMI as body weight/height2. Carotid pressure waveforms were recorded to derive time to reflection, reflection magnitude, and aortic augmentation index at baseline, and at 10 and 30 min postintervention. RESULTS:Foam rolling elicited reductions in aortic augmentation index at 10 min (P < 0.001) and 30 min (P = 0.021) postintervention. Reflection magnitude decreased 10 min after foam rolling (P < 0.001), whereas the time to reflection remained unchanged. Skeletal muscle index correlated negatively with reductions in augmentation index (r = -0.45, P = 0.021) and reflection magnitude (r = -0.41, P = 0.049) at 10 min, even after adjusting for age, sex, and BMI (both P < 0.05). CONCLUSION:Foam rolling acutely attenuated aortic pressure augmentation by reducing the magnitude rather than the timing of peripheral wave reflections. Moreover, individuals with greater muscle mass may derive more substantial cardiovascular benefits from foam rolling.
AIMS:Marinobufagenin (MBG), the endogenous cardiotonic inhibitor of the transmembrane adenosine triphosphatase sodium-potassium pump, is a steroid hormone with divergent effects on blood pressure and cardiovascular (CV) system. In response to sodium load, MBG stimulates natriuresis to compensate for body fluid overload but, in condition of sustained high sodium intake, its excessive production promotes a maladaptive pro-hypertensive effect. Since the role of MBG on the cardiac alterations frequently affecting hypertensive patients has been poorly investigated, we focused on gaining insight into this relationship in essential hypertension. METHODS:We studied the relationships between MBG, LV mass and geometry and investigated whether diuretic therapy modifies these associations in 180 incident-prevalent patients with essential hypertension. RESULTS:Serum MBG levels were significantly lower in hypertensive patients than in normotensive individuals (P = 0.005) and strongly associated with the mass and muscle component of the left ventricle. On multivariable linear regression models, left ventricular mass index and the cardiac measurements posterior wall thickness, interventricular septal thickness, mean wall thickness, relative wall thickness increased in parallel with the decrease in serum MBG levels (P ≤ 0.01). Coherently, in a multivariable logistic model, the odds of having cardiac remodeling/hypertrophy increased by 9% for each 0.1 nmol/l MBG reduction (odds ratio: 1.09, 95% confidence interval: 1.01-1.18, P = 0.03). Furthermore, diuretic therapy modified the link between MBG and cardiac biomarkers by acting as an amplifier of the harmful effect of low MBG levels on these measures. CONCLUSIONS:In patients with essential hypertension, lower circulating levels of MBG are associated with alterations in myocardial morphology whose severity is modified by the diuretic therapy that amplifies the noxious effect of low MBG levels. GRAPHICAL ABSTRACT:https://links.lww.com/HJH/D96.
BACKGROUND:Visit-to-visit variability (VVV) of blood pressure (BP) has been linked to adverse cardiovascular and kidney outcomes in various populations, but results in those with chronic kidney disease (CKD) have been inconsistent. METHODS:We evaluated VVV in Chronic Renal Insufficiency Cohort (CRIC) participants, using the coefficient of variation (CoV = standard deviation of SBP/mean SBP) calculated from BP measurements obtained at baseline visit through year 5 of the study. Cox proportional hazards models were used to assess the association of CoV with a composite cardiovascular outcome (myocardial infarction, stroke, peripheral artery disease, heart failure) and a composite kidney outcome (50% reduction in estimated glomerular filtration rate or end-stage kidney disease). RESULTS:Among 3891 participants (44% women, mean age 63 ± 10 years, mean CoV 10.3 ± 5.2%), 757 cardiovascular and 920 kidney events occurred during a median follow-up of 5.4 and 4.5 years, respectively. In unadjusted analyses, the upper tertile of CoV was associated with increased risk of both cardiovascular [hazard ratio 2.04, 95% confidence interval (CI) 1.70-2.43] and kidney outcomes (hazard ratio 1.62, 95% CI 1.38-1.89) compared to the lowest tertile. However, after adjustment for clinical and sociodemographic factors, higher CoV was significantly associated with cardiovascular outcomes (adjusted hazard ratio 1.25, 95% CI 1.04-1.52) but not kidney outcomes (adjusted hazard ratio 0.95, 95% CI 0.80-1.15). CONCLUSION:In this large CKD cohort, higher visit-to-visit BP variability was independently linked to adverse cardiovascular, but not kidney, outcomes.
OBJECTIVES:Activation of the intrarenal renin-angiotensin system (RAS) has been implicated in chronic kidney disease (CKD) pathophysiology. Although urinary angiotensinogen (AGT) is a noninvasive surrogate marker of intrarenal RAS activity, whether urinary AGT is associated with incident CKD remains unclear. We investigated the association between urinary AGT and incident CKD in community-dwelling adults without CKD. METHODS:We conducted a prospective cohort study of community-dwelling adults without CKD. Urinary AGT, urinary N-acetyl-β-d-glucosaminidase (NAG), urinary β2-microglobulin (β2-MG), urinary albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) were assessed at baseline. Incident CKD was defined according to established criteria based on eGFR and urinary ACR during follow-up. Associations between urinary AGT levels and incident CKD were examined using multivariable-adjusted Cox proportional hazards models. RESULTS:Among 197 participants without CKD at baseline, 22% developed incident CKD during a median follow-up of 4.9 years. Weak to moderate correlations were observed between urinary AGT levels and kidney-related markers at baseline, including an inverse correlation with eGFR (ρ = -0.21) and positive correlations with urinary ACR (ρ = 0.44), urinary NAG (ρ = 0.35), and urinary β2-MG (ρ = 0.56). Higher baseline urinary AGT levels were significantly associated with an increased risk of incident CKD [adjusted hazard ratio per 1-SD increase, 1.48; 95% confidence interval (CI), 1.02-2.16] after multivariable adjustment. CONCLUSION:Higher urinary AGT levels were associated with incident CKD in individuals with preserved kidney function, suggesting that urinary AGT may serve as a marker of early CKD risk.
OBJECTIVE:In previous studies involving older hypertensive adults, geriatric conditions with potential prognostic impact and outcomes of geriatric relevance (e.g., disability) remained largely unexplored. This study investigated predictors of all-cause mortality and incident disability in a real-world sample of older hypertensive outpatients undergoing comprehensive geriatric assessment. METHODS:We analyzed data from the longitudinal HYPER-FRAIL pilot study, involving hypertensive outpatients ≥75 years undergoing comprehensive geriatric assessment, office, ambulatory and home blood pressure (BP) measurements. Predictors of long-term all-cause mortality and incident disability in basic activities of daily living (BADL) were assessed using multivariate Cox and logistic regression analyses, respectively. RESULTS:Among 112 participants (mean age 81.2 years, 58% women, median follow-up 55 months), mortality was 25.9%. Baseline BADL disability, impaired physical performance and frailty independently predicted mortality. Stratified analyses showed that higher BP was associated with increased mortality risk only in patients with preserved autonomy in instrumental activities of daily living (IADL). Among those with IADL disability, office diastolic BP <80 mmHg and ambulatory 24 h systolic BP <130 mmHg were associated with increased mortality. Among 78 participants with baseline BADL autonomy, disability incidence was 39.7%. Predictors included baseline IADL and physical impairment, cognitive decline and ambulatory daytime hypotension. The association with hypotension was independent of falls or syncope, but not of dementia. CONCLUSIONS:Disability, impaired physical performance and frailty predicted all-cause mortality in older hypertensive outpatients. The association between BP and mortality varied by functional status, suggesting a modifying - possibly reversing - effect. Ambulatory hypotension was associated with incident disability. GRAPHICAL ABSTRACT:https://links.lww.com/HJH/D93.
In 2024, the European Society of Cardiology (ESC) hypertension guidelines introduced an "elevated blood pressure" category (120-139 and/or 70-89 mmHg), lowering the diastolic threshold from 85 to 70 mmHg. Its relevance for cardiovascular risk stratification in low-risk primary prevention remains uncertain. We conducted a cross-sectional study of 1394 adults undergoing standardized preventive health assessment in France, with office blood pressure (BP) measured using a validated oscillometric device. Participants were classified by ESC/ESH 2018 and ESC 2024 definitions. We quantified category shifts and compared the clinical, lifestyle and biological profile of individuals reclassified from 2018 optimal to 2024 elevated on the basis of diastolic BP ≥70 mmHg (systolic BP < 120 mmHg) vs. those remaining nonelevated. SCORE2, available in 61% of participants, was used as a supporting risk estimate. ESC 2024 classified 10.0% as nonelevated, 64.2% as elevated and 25.8% as hypertensive; 70% of previously "optimal" individuals became "elevated." Compared with nonelevated peers, the diastolic-only reclassified group differed only in age (45.5 vs. 42.7 years; P = 0.007), with no difference in sex, body mass index, lifestyle, cardiovascular history or biomarkers. Their slightly higher SCORE2 was attributable to higher systolic BP and age, and was no longer significant after adjustment for systolic BP. By contrast, individuals reclassified from normal to elevated had a less favorable cardiometabolic profile. Lowering the diastolic threshold to 70 mmHg produced substantial reclassification but did not identify an independent higher-risk phenotype when systolic BP remained < 120 mmHg, questioning the relevance of such a low diastolic threshold for elevated BP in the new ESC 2024 classification. Prospective outcome studies are needed.
BACKGROUND:The aim of this study was to characterize hypertension-associated cardiac damage in the blood pressure (BP) phenotypes sustained normotension (SNT), white coat hypertension (WCHT), masked hypertension (MHT) and sustained hypertension (SHT). METHODS:In a population-based study, 4115 individuals were examined with office and home BP measurement, computed tomography, coronary computed tomography angiography and echocardiography. The odds ratios of hypertension-associated cardiac damage in the BP phenotypes were analysed with SNT and SHT as references, respectively, for coronary artery calcium score (CACS) at least 100 and at least 300, Segment Involvement Score (SIS) at least 4, any significant (>50%) coronary stenosis, left ventricular ejection fraction (LVEF) less than 50%, E/e΄ ratio (E/e΄) at least 14, and global longitudinal strain (GLS) greater than -17 (men) or greater than -18 (women). RESULTS:The odds of having hypertension-associated cardiac damage were significantly higher for WCHT than for SNT [LVEF < 50%: OR 1.83 (1.17-2.86), CACS ≥ 100: OR 1.58 (1.19-2.11)], and for SHT than for SNT [LVEF < 50%: OR 2.34 (1.53-3.57), CACS ≥ 100: OR 1.52 (1.14-2.02)]. The odds of having hypertension-associated cardiac damage were also significantly higher for MHT than for SNT (LVEF < 50%: OR 2.68 (1.41-5.10), CACS ≥ 100: OR 2.15 (1.37-3.38) and CACS ≥ 300: OR 2.34 (2.21-4.52)]. CONCLUSION:The prevalence of hypertension-associated cardiac damage was higher in WCHT and in MHT compared to SNT. WCHT and MHT should therefore be considered when assessing cardiovascular risk, and BP should be measured both in the office and at home when diagnosing and monitoring hypertension.
AIM:An updated meta-analysis targeting the prevalence of left ventricular hypertrophy (LVH), a cardinal marker of hypertensive heart disease (HHD), over the last 15 years is lacking. Thus, we analyzed the literature in order to provide a comprehensive information on LVH prevalence, as assessed by echocardiography, in the hypertensive setting. METHODS:The PubMed, OVID-MEDLINE, and Cochrane Library databases were analyzed to search English-language articles published from 1 January 2011 up to 31 December 2025. Studies were identified by using MeSH terms and crossing the following search items: 'left ventricular hypertrophy', 'left ventricular mass', 'hypertensive heart disease', 'echocardiography', 'hypertension', and 'subclinical cardiac damage'. RESULTS:A total of 51 studies including 74 632 hypertensive patients were considered. Overall, the prevalence of LVH in the pooled cohort, defined according to criteria recommended by echocardiographic guidelines, was 36.6% (95% CI: 33.4-40%). Data provided by 18 studies ( n = 40 108 patients) showed that the probability of having LVH was lower in men than in women (OR = 0.62, CI: 0.48-0.80, P < 0.0001). Among patients with LVH (17 studies), the risk of concentric LVH was almost twice as high as eccentric (OR = 1.94, CI: 1.52-2.49, P < 0.0001). CONCLUSION:Our meta-analysis suggests that the high contemporary prevalence of LVH reflects the failure of therapeutic strategies worldwide in the prevention and treatment of HHD. From a clinical perspective, these data imply the need for a more aggressive treatment of hypertension and related cardiovascular risk factors leading to LVH, especially in women.
Hypertension in sub-Saharan Africa is escalating, with many cases undiagnosed and poorly controlled, even among children, despite its significant contribution to cardiovascular disease. Poor blood pressure control is largely due to limited national guidelines, underfunded programs, and a shortage of trained health professionals. Simplified protocols for non-physician health workers, who deliver most of the primary care, are essential. Cultural myths and misconceptions further delay care, underscoring the need for community-based education. Early and opportunistic screening, including in schools, markets, and places of worship, is vital across the life course. Sustainable progress depends on tailored strategies, investment in equipment and training, and leveraging existing infrastructure to improve hypertension detection and management. Africa-centred hypertension guidelines are now a priority because international models fail to address the continent's unique clinical, cultural and resource realities. The African Regional Advisory Group of the International Society of Hypertension worked with the Pan African Society of Cardiology to develop simplified protocols for primary care, particularly for non-physician health care workers, by considering the special situation and condition for managing the vast majority of cases within hypertension in Africa.
This study aimed to quantify the effects of exercise on aerobic capacity in people with prehypertension or hypertension and to identify exercise prescription parameters that optimize improvements. A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and Scopus from inception to 24 October 2025. Data were pooled using standardized mean differences (SMDs) with 95% confidence intervals (CI). Fifteen studies met the inclusion criteria. Exercise significantly improved aerobic capacity in people with prehypertension or hypertension (SMD = 0.88; 95% CI: 0.61-1.15; P < 0.00001), with multicomponent training demonstrating superior efficacy. Exploratory subgroup analyses suggest that longer programs (≥12 weeks), lower frequency (<3 sessions/week), 60-min sessions or longer, total weekly exercise less than 180 min, and professional supervision may be associated with better outcomes.
BACKGROUND:Mutations in the breast cancer susceptibility gene 2 ( BRCA2 ) are well known to increase the risk of breast and ovarian cancers. Emerging evidence indicates that BRCA2 mutation carriers exhibit increased vascular disorder and may develop endothelial dysfunction, a key mechanism underlying hypertension. Angiotensin II (Ang II), a central effector of the renin-angiotensin system, is a key regulator of blood pressure and a major driver of hypertension, promoting endothelial injury through oxidative stress, inflammation, and impaired nitric oxide (NO) bioavailability. However, the role of endothelial BRCA2 in Ang II-induced endothelial dysfunction remains unknown. METHODS:BRCA2 was silenced in cultured endothelial cells and following Ang II treatment, ROS generation, DNA damage, apoptosis, inflammation, NO production, migration, angiogenic capacity, Ang II receptors and related signaling pathways were assessed. RESULTS:BRCA2 deficiency exacerbated Ang II-induced increases in ROS, DNA damage, and apoptosis, along with impaired functional capacity, including reduced migration and angiogenesis. NO production was suppressed, accompanied by increased micronuclei formation and enhanced c-Jun N-terminal kinase (JNK) activation. In addition, both BRCA2 loss and Ang II treatment upregulated the Ang II receptor AT1R. Pharmacological inhibition of AT1R attenuated Ang II-induced increases in DNA damage and apoptosis in BRCA2 -deficient endothelial cells. CONCLUSION:These findings provide the first pharmacogenomic evidence that BRCA2 deficiency sensitizes endothelial cells to Ang II-induced dysfunction, suggesting that BRCA2 mutation carriers may be at increased risk for hypertension-associated cardiovascular complications.
Aldosterone synthase inhibitors (ASIs) demonstrated significant blood pressure (BP) lowering efficacy in patients with uncontrolled hypertension, but evidence in chronic kidney disease (CKD) remains limited. This meta-analysis explores the effects of selective ASIs on BP levels in CKD. Secondary outcomes were albuminuria (UACR), eGFR change and hyperkalemia incidence. Five RCTs (1,148 patients) were included; 2 used baxdrostat, 2 lorundrostat, and 1 study used vicadrostat. Treatment with ASIs was associated with a significant placebo-adjusted reduction in SBP of-7.9 mmHg [95% confidence interval (CI) -10.0 to -5.9, I2 = 0%] and DBP of -3.1 mmHg (95% CI -5.9 to -0.2, I2 = 62%) and reduced UACR by -31.7% (95% CI -54.5 to -8.9, I2 = 91%). The pooled placebo-adjusted eGFR change was -2.05 ml/min/1.73 m 2 (95% CI -3.15 to -0.95, I2 = 0%). The risk of hyperkalemia was higher with ASIs, but with high heterogeneity (risk ratio, 4.04 [95% CI 0.94 to 17.35], I2 = 76%). In conclusion, selective ASIs present a potential treatment option for BP control and albuminuria reduction in patients with CKD.
Many primary aldosteronism (PA) patients harbor concomitant mild autonomous cortisol secretion (MACS), termed "Connshing syndrome." The prevalence and cardiometabolic impact of this co-secretion have not been quantitatively synthesized. To determine the pooled prevalence of MACS in PA and evaluate its association with cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and obesity. PubMed, Embase, Cochrane, Web of Science, and Scopus through January 2026. Following PRISMA 2020 and MOOSE guidelines (PROSPERO: CRD420261334965), studies reporting MACS prevalence [post-1 mg dexamethasone suppression test (DST) cortisol ≥1.8 μg/dl] in PA were included. Prevalence was pooled using random-effects models. Odds ratios (ORs) were calculated for cardiometabolic outcomes. Certainty was evaluated using GRADE. Fourteen studies (2356 patients) were included. Pooled MACS prevalence was 26.2% [95% confidence interval (CI): 24.1-28.4; I2 = 24.2%; prediction interval: 21.6-31.4%], consistent across European (27.0%) and East Asian (25.2%) cohorts ( P = 0.62). MACS + PA patients had higher odds of CV events (OR 1.60; 95% CI: 1.07-2.38; P = 0.021) and T2DM (OR 1.37; 95% CI: 1.00-1.86; P = 0.048), but not obesity (OR 1.10; P = 0.411). Sensitivity analyses confirmed robustness. GRADE certainty was moderate for prevalence and low for CV events. Approximately one in four PA patients has MACS, associated with a 60% higher CV event risk. These findings support routine DST screening in PA and have implications for perioperative management and cardiometabolic risk stratification.
