Left ventricular structure and function in relation to sodium dietary intake and renal handling in untreated Chinese patients

Gupta D.K., Lewis C.E., Varady K.A., Su Y.R., Madhur M.S., Lackland D.T., Reis J.P., Wang T.J., Lloyd-Jones D.M., Allen N.B.

ImportanceDietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied.ObjectivesTo examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use.Design, Setting, and ParticipantsProspectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets.InterventionHigh-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets.Main Outcomes and MeasuresAverage 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure.ResultsAmong the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants’ median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as “salt sensitive.” At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively.Conclusions and RelevanceDietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events.Trial RegistrationClinicalTrials.gov Identifier: NCT04258332

Carluccio E., Dini F.L., Correale M., Dattilo G., Ciccarelli M., Vannuccini F., Sforna S., Pacileo G., Masarone D., Scelsi L., Ghio S., Tocchetti C.G., Mercurio V., Brunetti N.D., Nodari S., et. al.

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), treatment with sacubitril–valsartan (S/V) may reverse left ventricular remodeling (rLVR). Whether this effect is superior to that induced by other renin–angiotensin system (RAS) inhibitors is not well known. Methods HFrEF patients treated with S/V (n = 795) were compared, by propensity score matching, with a historical cohort of 831 HFrEF patients (non-S/V group) treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (RAS inhibitors). All patients were also treated with beta-blockers and shared the same protocol with repeat echocardiogram 8–12 months after starting therapy. The difference-in-difference (DiD) analysis was used to evaluate the impact of S/V on CR indices between the two groups. Results After propensity score matching, compared to non-S/V group (n = 354), S/V group (n = 354) showed a relative greater reduction in end-diastolic and end-systolic volume index (ESVI), and greater increase in ejection fraction (DiD estimator =  + 5.42 mL/m2, P = 0.0005; + 4.68 mL/m2, P = 0.0009, and + 1.76%, P = 0.002, respectively). Reverse LVR (reduction in ESVI ≥ 15% from baseline) was more prevalent in S/V than in non-S/V group (34% vs 26%, P = 0.017), while adverse LVR (aLVR, increase in ESVI at follow-up ≥ 15%) was more frequent in non-S/V than in S/V (16% vs 7%, P < 0.001). The beneficial effect of S/V on CR over other RAS inhibitors was appreciable across a wide range of patient’s age and baseline end-diastolic volume index, but it tended to attenuate in more dilated left ventricles (P for interaction = NS for both). Conclusion In HFrEF patients treated with beta-blockers, sacubitril/valsartan is associated with a relative greater benefit in LV reverse remodeling indices than other RAS inhibitors. Graphical abstract

Wang J., Zhang W., Li Y., Liu L.

The past two to three decades have seen a steady increase in the prevalence of hypertension in China, largely owing to increased life expectancy and lifestyle changes (particularly among individuals aged 35–44 years). Data from the China hypertension survey conducted in 2012–2015 revealed a high prevalence of grade 3 hypertension (systolic blood pressure ≥180 mmHg and diastolic blood pressure ≥110 mmHg) in the general population, which increased with age to up to 5% among individuals aged ≥65 years. The risk profile of patients with hypertension in China has also been a subject of intense study in the past 30 years. Dietary sodium and potassium intake have remained largely the same in China in the past three decades, and salt substitution strategies seem to be effective in reducing blood pressure levels and the risk of cardiovascular events and death. However, the number of individuals with risk factors for hypertension and cardiovascular disease in general, such as physical inactivity and obesity, has increased dramatically in the same period. Moreover, even in patients diagnosed with hypertension, their disease is often poorly managed owing to a lack of patient education and poor treatment compliance. In this Review, we summarize the latest epidemiological data on hypertension in China, discuss the risk factors for hypertension that are specific to this population, and describe several ongoing nationwide hypertension control initiatives that target these risk factors, especially in the low-resource rural setting. The prevalence of hypertension in China has risen steadily in the past two to three decades. In this Review, Wang and colleagues summarize the latest epidemiological data on hypertension in China, describe the risk factors for hypertension that are relevant to this population, and provide an overview of initiatives aimed at improving awareness, treatment and control of hypertension, especially in the low-resource rural setting.

ElSayed N.A., Aleppo G., Aroda V.R., Bannuru R.R., Brown F.M., Bruemmer D., Collins B.S., Hilliard M.E., Isaacs D., Johnson E.L., Kahan S., Khunti K., Leon J., Lyons S.K., Perry M.L., et. al.

The American Diabetes Association (ADA) “Standards of Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Huang Q., Cheng Y., Guo Q., Liu C., Kang Y., Sheng C., Li Y., Wang J.

Advanced glycation end product (AGE) clearance may cause renal tubular injuries, such as changes in sodium reabsorption. We hypothesize that AGEs interact with sodium metabolism to influence blood pressure (BP). The study participants were outpatients who were suspected of having hypertension but had not been treated with antihypertensive medication. Clinic and ambulatory blood pressures were measured at baseline (n = 989) and during follow-up (median, 4.4 years, n = 293). Plasma AGE concentrations were measured by enzyme-linked immunosorbent assay. Twenty-four-hour urine was collected for measurements of creatinine, sodium and lithium. In a cross-sectional analysis (n = 989), subjects in the top quintile versus quintiles 1–4 of plasma AGE concentration had significantly (P ≤ 0.004) lower fractional excretion of lithium (18.3% vs. 21.6%) and fractional distal reabsorption rate of sodium (95.0% vs. 95.8%) but similar BP (P ≥ 0.25). However, there was an interaction between plasma AGE concentration and urinary sodium excretion in relation to diastolic BP (P ≤ 0.058). Only in participants with low urinary sodium chloride excretion (≤6 grams/day, n = 189), clinic (84.3 vs. 80.2 mmHg), 24-h (83.9 vs. 80.4 mmHg), daytime (87.8 vs. 84.8 mmHg) and nighttime (75.1 vs. 72.1 mmHg) diastolic BP at baseline were higher (P ≤ 0.05) in the top quintile than in quintiles 1–4 of plasma AGE concentration. In the longitudinal study (n = 383), similar trends were observed, with significant (P ≤ 0.05) differences in the increment in daytime diastolic BP (6.8 vs. −1.7 mmHg) and incidence of ambulatory and treated hypertension (hazard ratio 3.73) during follow-up. In conclusion, AGEs were associated with high BP, probably via enhanced proximal sodium handling and on low dietary sodium intake.

Ma Y., He F.J., Sun Q., Yuan C., Kieneker L.M., Curhan G.C., MacGregor G.A., Bakker S.J., Campbell N.R., Wang M., Rimm E.B., Manson J.E., Willett W.C., Hofman A., Gansevoort R.T., et. al.

The relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of multiple days is considered to be an accurate method.We included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis.Among 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval [CI], 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94).Higher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).

Sheng Y., Li M., Xu M., Zhang Y., Xu J., Huang Y., Li X., Yao G., Sui W., Zhang M., Zhang Y., Zhang C., Zhang Y., Zhang M.

Abstract Aims To investigate differences in the prevalence of left ventricular (LV) and left atrial (LA) remodelling in hypertensive patients using various thresholds defined by international guidelines and data from the Echocardiographic Measurements in Normal Chinese Adults (EMINCA) study and different indexation methods. Methods and results LV mass (LVM), relative ventricular wall thickness, and LA volume (LAV) were measured using 2D echocardiography in 612 healthy volunteers selected from the EMINCA study population and 306 adult Chinese patients with hypertension who were age- and gender-matched using propensity score-matched analysis. LVM and LAV values were indexed to body surface area (BSA), height2.7, height1.7, and height2 recommended by guidelines or investigators. Using a previously reported method, LV geometry was divided into normal geometry, concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. The prevalence of LV hypertrophy (LVH) and LV geometric patterns in hypertensive patients were compared using different thresholds and indexation methods. Echocardiographic thresholds from guidelines and healthy volunteers exhibited notable differences, particularly for LAV indexed to height2 and for LVM indexed to height1.7, which resulted in a significantly lower prevalence of LA dilatation and LVH in healthy volunteers. The total proportion of abnormal LV geometric patterns was significantly lower with thresholds from healthy volunteers than from guidelines when LVM was indexed to BSA, height1.7, and height2,7. Conclusion Using current echocardiographic thresholds and indexing methods recommended by guidelines may lead to significant misdiagnosis of LA dilatation, and abnormal LV geometry in Chinese patients with hypertension, and thresholds based on ethnic-specific normal echocardiographic reference values and an accurate indexing algorithm are warranted.

Natali A., Nesti L., Tricò D., Ferrannini E.

The impressive results of recent clinical trials with glucagon-like peptide-1 receptor agonists (GLP-1Ra) and sodium glucose transporter 2 inhibitors (SGLT-2i) in terms of cardiovascular protection prompted a huge interest in these agents for heart failure (HF) prevention and treatment. While both classes show positive effects on composite cardiovascular endpoints (i.e. 3P MACE), their actions on the cardiac function and structure, as well as on volume regulation, and their impact on HF-related events have not been systematically evaluated and compared. In this narrative review, we summarize and critically interpret the available evidence emerging from clinical studies. While chronic exposure to GLP-1Ra appears to be essentially neutral on both systolic and diastolic function, irrespective of left ventricular ejection fraction (LVEF), a beneficial impact of SGLT-2i is consistently detectable for both systolic and diastolic function parameters in subjects with diabetes with and without HF, with a gradient proportional to the severity of baseline dysfunction. SGLT-2i have a clinically significant impact in terms of HF hospitalization prevention in subjects at high and very high cardiovascular risk both with and without type 2 diabetes (T2D) or HF, while GLP-1Ra have been proven to be safe (and marginally beneficial) in subjects with T2D without HF. We suggest that the role of the kidney is crucial for the effect of SGLT-2i on the clinical outcomes not only because these drugs slow-down the time-dependent decline of kidney function and enhance the response to diuretics, but also because they attenuate the meal-related anti-natriuretic pressure (lowering postprandial hyperglycemia and hyperinsulinemia and preventing proximal sodium reabsorption), which would reduce the individual sensitivity to day-to-day variations in dietary sodium intake.

Neal B., Wu Y., Feng X., Zhang R., Zhang Y., Shi J., Zhang J., Tian M., Huang L., Li Z., Yu Y., Zhao Y., Zhou B., Sun J., Liu Y., et. al.

Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain.We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia.A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P

Chen Y., Xu T., Xu J., Zhu L., Li Y., Wang J.

We investigated the myocardial work derived from left ventricular pressure-strain loop in patients with primary aldosteronism or primary hypertension. We enrolled 50 patients with primary aldosteronism, 50 age- and sex-matched patients with primary hypertension, and 25 normotensive control subjects. We performed transthoracic echocardiography and speckle-tracking echocardiography-based left ventricular pressure-strain loop analysis to evaluate cardiac structure and function. Patients with primary aldosteronism and those with primary hypertension had similar clinic and ambulatory blood pressures, except that the former had a significantly (P = 0.03) higher nighttime systolic blood pressure. All subjects had normal left ventricular ejection fraction (66.4 ± 4.7%). Patients with primary aldosteronism had a greater left ventricular mass index than those with primary hypertension and the normal controls (111.0 ± 21.6 g/m2 versus 95.7 ± 17.7 and 77.9 ± 13.5 g/m2, respectively, P < 0.001). The global myocardial work index (GWI, 2336 ± 333, 2366 ± 288, and 2292 ± 249 mmHg%, respectively), and global constructive work (GCW, 2494 ± 325, 2524 ± 301, and 2391 ± 193 mmHg%, respectively), were comparable in the three groups (P ≥ 0.18). However, the global work efficiency (GWE) differed significantly (P < 0.001), being lowest in primary aldosteronism (91.1 ± 2.7%), intermediate in primary hypertension (93.5 ± 2.5%) and highest in controls (95.3 ± 1.5%). The opposite was true for the global wasted work (GWW) (205.6 ± 74.6, 142.0 ± 56.4 and 99.4 ± 33.7 mmHg%, respectively, P < 0.001). GWE was significantly correlated with the logarithmically transformed plasma concentration and the urinary excretion of aldosterone in patients with primary aldosteronism or primary hypertension (r = −0.43 for both, P < 0.001). The associations remained statistically significant (P ≤ 0.04) after further adjustment for several factors, including left ventricular mass index and clinic or nighttime blood pressure. In conclusion, GWE decreased and GWW increased in primary hypertension and further in primary aldosteronism, probably because of the adrenal aldosterone hypersecretion and the left ventricular mass index increase, while GWI and GCW were similar, indicating that similar and normalized total myocardial work might be a compensation in hypertension at the expense of work efficiency.

Filippini T., Malavolti M., Whelton P.K., Naska A., Orsini N., Vinceti M.

Background: The relationship between dietary sodium intake and blood pressure (BP) has been tested in clinical trials and nonexperimental human studies, indicating a direct association. The exact shape of the dose–response relationship has been difficult to assess in clinical trials because of the lack of random-effects dose–response statistical models that can include 2-arm comparisons. Methods: After performing a comprehensive literature search for experimental studies that investigated the BP effects of changes in dietary sodium intake, we conducted a dose–response meta-analysis using the new 1-stage cubic spline mixed-effects model. We included trials with at least 4 weeks of follow-up; 24-hour urinary sodium excretion measurements; sodium manipulation through dietary change or supplementation, or both; and measurements of systolic and diastolic BP at the beginning and end of treatment. Results: We identified 85 eligible trials with sodium intake ranging from 0.4 to 7.6 g/d and follow-up from 4 weeks to 36 months. The trials were conducted in participants with hypertension (n=65), without hypertension (n=11), or a combination (n=9). Overall, the pooled data were compatible with an approximately linear relationship between achieved sodium intake and mean systolic as well as diastolic BP, with no indication of a flattening of the curve at either the lowest or highest levels of sodium exposure. Results were similar for participants with or without hypertension, but the former group showed a steeper decrease in BP after sodium reduction. Intervention duration (≥12 weeks versus 4 to 11 weeks), type of study design (parallel or crossover), use of antihypertensive medication, and participants’ sex had little influence on the BP effects of sodium reduction. Additional analyses based on the BP effect of difference in sodium exposure between study arms at the end of the trial confirmed the results on the basis of achieved sodium intake. Conclusions: In this dose–response analysis of sodium reduction in clinical trials, we identified an approximately linear relationship between sodium intake and reduction in both systolic and diastolic BP across the entire range of dietary sodium exposure. Although this occurred independently of baseline BP, the effect of sodium reduction on level of BP was more pronounced in participants with a higher BP level.

Kang Y., Cheng Y., Guo Q., Sheng C., Huang Q., Xu T., Li Y., Wang J.

Abstract BACKGROUND We investigated proximal and distal renal tubular sodium handling, as assessed by fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa), in relation to environmental and genetic factors in untreated patients. METHODS Our study participants were suspected hypertensive patients being off antihypertensive medication for ≥2 weeks and referred for 24-hour ambulatory blood pressure monitoring. We collected serum and 24-hour urine for measurement of sodium, creatinine, and lithium concentration, and calculated FELi and FDRNa. We genotyped 19 single-nucleotide polymorphisms associated with renal sodium handling or blood pressure using the ABI SNapShot method. RESULTS The 1,409 participants (664 men, 47.1%) had a mean (±SD) age of 51.0 ± 10.5 years. After adjustment for host factors, both FELi and FDRNa were significantly (P ≤ 0.01) associated with season and humidity, explaining ~1.3% and ~3.5% of the variance, respectively. FELi was highest in autumn and lowest in summer and intermediate in spring and winter (P = 0.007). FDRNa was also highest in autumn but lowest in winter and intermediate in spring and summer (P &lt; 0.001). Neither FELi nor FDRNa was associated with outdoor temperature or atmospheric pressure (P ≥ 0.13). After adjustment for host and environmental factors and Bonferroni multiple testing, among the 19 studied genetic variants, only rs12513375 was significantly associated with FELi and FDRNa (P ≤ 0.004) and explained about 1.7% of the variance. CONCLUSIONS Renal sodium handling as measured by endogenous lithium clearance was sensitive to major environmental and genetic factors. Our finding is toward the use of these indexes for the definition of renal tubular dysfunction.

Zannad F., Ferreira J.P., Pocock S.J., Anker S.D., Butler J., Filippatos G., Brueckmann M., Ofstad A.P., Pfarr E., Jamal W., Packer M.

Background Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials. Methods We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model. Findings Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p Interpretation The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF. Funding Boehringer Ingelheim.

Chen Y., Xu T., Xu J., Zhu L., Li Y., Wang J.

OBJECTIVE We investigated right ventricular function using speckle tracking echocardiography (STE) in patients with primary aldosteronism. METHODS Our study included 51 primary aldosteronism patients and 50 age and sex-matched primary hypertensive patients. We performed two-dimensional echocardiography to measure cardiac structure and function. We performed STE offline analysis on right ventricular four-chamber (RV4CLS) and free wall longitudinal strains (RVFWLS). RESULTS Primary aldosteronism patients, compared with primary hypertensive patients, had a significantly (P ≤ 0.045) greater left ventricular mass index (112.0 ± 22.6 vs. 95.8 ± 18.5 g/m) and left atrial volume index (26.9 ± 6.0 vs. 24.7 ± 5.6 ml/m) and higher prevalence of left ventricular concentric hypertrophy (35.3 vs. 12.0%), although they had similarly normal left ventricular ejection fraction (55-77%). Primary aldosteronism patients also had a significantly (P ≤ 0.047) larger right atrium and ventricle, lower tricuspid annular plane systolic excursion, and higher E/E't (the peak early filling velocity of trans-tricuspid flow to the peak early filling velocity of lateral tricuspid annulus ratio), estimated pulmonary arterial systolic pressure and right ventricular index of myocardial performance. On the right ventricular strain analysis, primary aldosteronism patients had a significantly (P 

He F.J., Tan M., Ma Y., MacGregor G.A.

There is strong evidence for a causal relationship between salt intake and blood pressure. Randomized trials demonstrate that salt reduction lowers blood pressure in both individuals who are hypertensive and those who are normotensive, additively to antihypertensive treatments. Methodologically robust studies with accurate salt intake assessment have shown that a lower salt intake is associated with a reduced risk of cardiovascular disease, all-cause mortality, and other conditions, such as kidney disease, stomach cancer, and osteoporosis. Multiple complex and interconnected physiological mechanisms are implicated, including fluid homeostasis, hormonal and inflammatory mechanisms, as well as more novel pathways such as the immune response and the gut microbiome. High salt intake is a top dietary risk factor. Salt reduction programs are cost-effective and should be implemented or accelerated in all countries. This review provides an update on the evidence relating salt to health, with a particular focus on blood pressure and cardiovascular disease, as well as the potential mechanisms. • Our current high salt intake is among the top 3 dietary risk factors worldwide. • Population-wide reduction in salt intake lowers population BP and alleviates the burden of CVD and other chronic diseases. • Paradoxical findings from methodologically flawed studies should not be used to refute the strong evidence on the benefits of salt reduction. • Worldwide salt-reduction efforts should be reinforced to save millions of people dying unnecessarily from stroke and heart disease each year.

Iannilli E., Fürer R., Welge-Lüssen A., Hummel T.

Excessive dietary sodium intake is a major risk factor for hypertension, prompting interest in potassium chloride (KCl) as a sodium chloride (NaCl) alternative. While KCl preserves saltiness, its neural processing compared to NaCl remains underexplored. This study investigates the neural correlates of taste perception for NaCl, KCl, and their mixture using gustatory event-related potentials (ERPs) in a sample of 28 healthy young adults. Participants rated the intensity, saltiness, and pleasantness of the stimuli, which were matched for iso-intensity and iso-pleasantness. High-density EEG data revealed distinct microstate patterns associated with each condition, particularly in the later stages of processing, which align with the endogenous phases of taste perception. Source localization identified the insula and opercular regions as primary sites for gustatory processing, with specific differences in activation patterns between NaCl and KCl. These findings suggest that while KCl elicits comparable behavioral responses to NaCl, its neural representation involves unique processes that may reflect its distinct chemical properties. This study advances our understanding of the neural dynamics of salt taste perception, providing insights into the potential use of KCl as a potentially healthier alternative in dietary interventions.

Kubozono T.

Muiesan M.L., Agabiti-Rosei C., Buso G.