In the IL group, the implant was loaded on the same day as insertion, whereas it was loaded 3 months after insertion in the CL group. Magnetic attachments were used to retain all overdentures to the implants. MP, measured by a piece of color-changeable chewing gum and a gummy jelly test, and maximum occlusal force, measured using an occlusal force measuring device, were assessed in both groups at baseline and at 3-, 4-, and 5-year follow-ups.The appropriate loading protocol to improve masticatory performance (MP) is still unclear in elderly patients and two-implant overdentures (2-IODs) wearers. This study aimed to compare the long-term MP and maximum occlusal force of immediate loading (IL) and conventional loading (CL) of 2-IODs retained by magnetic attachments. Nineteen edentulous patients were randomly assigned to either an IL (P = 0.036). The maximum occlusal force revealed a significant correlation with MP, both with the color-changeable chewing gum and gummy jelly at 5 years.No significant differences were observed in the MP and the maximum occlusal force between the IL and CL groups at any time point. However, a significantly higher MP was observed at the 3-year time point in the IL group (After long-term observation, no significant differences in MP and maximum occlusal force were observed between the IL and CL groups. However, compared to pre-implant insertion of the complete denture, the MP in the IL group significantly improved at 3 years. Furthermore, the maximum occlusal force was significantly correlated with MP at 5 years.UMIN000009889. Registered on 28 January 2013.UMIN,  In numerous studies, it has been observed that the masticatory performance (MP) has improved significantly in patients using mandibular overdentures and dental implants compared to patients using complete dentures (CDs) –5. In thAccording to the conventional loading (CL) protocol, the overdenture is attached during a second procedure after a healing period of 3–6 months, with a two-stage (submerged) implant placement protocol –18. For Nevertheless, more robust evidence is needed to determine whether IL or CL provides satisfactory results over time for the unsplinted mandibular 2-IODs. There are no RCTs comparing the MP of mandibular 2-IODs retained by magnetic attachment with IL to that with the CL approach at the 5-year follow-up period in the current literature. Notably, these outcomes with a 3-year follow-up have been published, and only one difference was found between IL and CL in the gummy jelly test after 6 months . The preThis study was a randomized, unblinded, parallel, and controlled clinical study with a 5-year follow-up. Participants underwent oral rehabilitation with 2-IODs at the Department of Gerodontology and Oral Rehabilitation clinic in Tokyo Medical and Dental University (TMDU) between 2012 and 2013. All study participants provided written informed consent. This study was conducted in accordance with the guidelines of the Declaration of Helsinki. The recruitment and treatment protocols were conducted according to the Ethical Review Committee of the Faculty of Dentistry, TMDU (registration number 693). This study was registered with the University Hospital Medical Information Network (UMIN) Center (UMIN000009889).Nineteen participants were enrolled in this RCT. The inclusion criteria were completely edentulous mandible and any opposing maxillary remaining teeth conditions, edentulous mandible for at least 6 months, no bone augmentation requirement, and good oral hygiene. The exclusion criteria included the presence of any systemic conditions that included compromised implant surgery, a history of chemotherapy or radiotherapy to the head and neck region, a history of taking bisphosphonate, and heavy smoker status.n=10) [The participants were randomly assigned to either the test group (IL), where the implants were immediately loaded, or the control group (CL), where the implants were submerged in the mucosa and loaded after 3 months of healing. A preoperative prosthetic evaluation of the existing prostheses was performed by a certified prosthodontist (M. K). A randomized treatment allocation was executed using a stratified randomization method to ensure pretreatment comparability of the groups with respect to age, gender, and the American College of Prosthodontists (ACP) classification . A detain=10) .The surgical and prosthetic procedures utilized in this study followed the protocols described in a previous report . The parMP was measured by a piece of color-changeable chewing gum and a gummy jelly test in addition to measurements of maximum occlusal force in all participants before implant placement (baseline) and at 3, 4, and 5 years after implant placement.L*, a*, and b* values were measured using a colorimeter  using the CIECLB color system at five points: the center and approximately 3 mm above, below, to the right, and to the left of the center. ΔE values were evaluated using the following formula:Color-changeable chewing gum  was evaluated, as described by Hama et al. . The parN) was calculated using the following formula and defined as the evaluation value [The number of chewing cycles  was used as the test item. The participants were instructed to chew the gummy jelly 30 times. Then, the patients expectorated the comminuted jelly as thoroughly as possible into a paper cup. After that, the comminuted gummy jelly was evaluated on a scale of 1–10 using the visual scoring methods described by Nokubi et al. .The maximum occlusal force was measured using an occlusal force measuring device . The devices were positioned unilaterally on the right and left sides of the first molar. Participants were instructed to bite as hard as possible on the device for 3 s. The measurements were repeated three times on each side. The average of the highest unilateral right and left measurements was used for data analysis.t-test and the chi-square test. The Mann-Whitney U test was used to analyze differences in MP and maximum occlusal force between the two loading groups. The differences in the MP and maximum occlusal force between the baseline and 3, 4, and 5 years within each group were compared using the Wilcoxon signed-rank test. The Bonferroni correction method was applied for multiple comparisons. Pearson correlations were performed to determine the association between the maximum occlusal force and MP at the 5-year time point. Statistical significance was set at P < 0.05.All statistical analyses were performed using SPSS software version 24 . The normality of the data was tested using the Kolmogorov-Smirnov test. The baseline characteristics of the participants were compared using the non-paired The patient flow diagram and allocation during the study are reported in Fig. Table r = 0.676, P = 0.007, Fig. r = 0.537, P = 0.025, Fig. r) with color-changeable chewing gum tended to be larger than that with gummy jelly.A Pearson correlation test was carried out to evaluate the correlation of MP and maximum occlusal force, and the correlation was statistically significant. A statistically significantly positive correlation between the maximum occlusal force and MP, both with color-changeable chewing gum  than with gummy jelly . Yamada et al. [The results of this study indicated a positive correlation between the MP and the maximum occlusal force at the 5-year follow-up. According to Fontijn-Tekamp et al. , a signia et al.  reportedA post hoc analysis indicated that the statistical power for detecting differences in MP between the two loading groups for the 5-year evaluation period was 0.15, with a large effect size of 0.57. However, the power statistic value was quite small, which was attributed to the small sample size. Thus, this work should be considered a preliminary study. In a future study, an increase in the sample size of each group to 50 participants would increase substantially the power statistic value to 0.80.One of the limitations of the present study was the small sample size; although participants had a long follow-up period, a single participant could have a large influence on the study results. However, the change in oral masticatory function could have been demonstrated in a much larger group of participants. Thus, the investigation should be considered a preliminary study. Nonetheless, numerous confounding factors may have affected the long-term outcomes reported, such as inconsistency of the participants’ maxillary occlusion status, elevator muscles, oral motor function, food texture, and food amount for each masticatory cycle. These confounding factors should be considered in future RCTs.After the long-term observation of 2-IODs with magnetic attachment, no significant differences in MP and maximum occlusal force were observed between the IL and CL.Compared to pre-implant insertion of CD, the MP and maximum occlusal force tended to improve, and the MP measured by color-changeable chewing gum significantly increased at 3 years.At 5 years, the maximum occlusal force was significantly correlated with the MP, both with the color-changeable chewing gum and gummy jelly.Based on the findings of this current study, the following conclusions were observed:


The kidney is central for maintaining water balance. As a corollary, patients with impaired kidney function are prone to pathological fluid volumes. Total body water (TBW) is distributed between the extracellular (ECW) and intracellular fluid compartments (ICW). In clinical practice, the judgment of hydration status does not allow to distinguish between ECW and ICW. Here, we evaluate the hydration status in children with chronic kidney disease by analyzing TBW, ECW, and ICW.Hydration was quantified using whole-body bioimpedance spectroscopy (BCM) in 128 outpatients . Forty-two were transplanted (TPL), 43 suffered from chronic kidney disease without kidney replacement therapy (CKD), 21 were on peritoneal dialysis (PD), and 22 on hemodialysis (HD). HD patients were investigated before, after, and sequentially during dialysis.p < 0.001, n = 22) correlated with the change in body weight (R2 = 0.62). The kinetics of fluid compartment changes assessed twice in six HD patients revealed a reproducible linear decay of the ECW/ICW ratio due to an increase of ICW and a decrease of ECW.The ECW and ICW values obtained by BCM were of the same magnitude as those from the literature using isotope dilution. When compared with a healthy control group, TBW was increased in 9 TPL, 9 CKD, 1 PD, and 11 HD patients before but in none after dialysis. The decline of overhydration during dialysis (BCM quantifies TBW and acute changes of ECW and ICW in children with chronic kidney failure. The clinical utility of measuring TBW, ECW, and ICW should be defined in the future. Patients with impaired kidney function have a high risk of chronic hypervolemia . ChronicFor several years, novel technologies have been in process to be developed for the quantitative assessment of the fluid status in humans. Among these techniques, whole-body, single- or multi-frequency bioimpedance spectroscopy are versatile noninvasive approaches for obtaining instant information about the body composition . As indiIn the present investigation, the fluid status was quantified by the BCM in an unselected outpatient cohort of 128 children with kidney failure with and without kidney replacement therapy. Furthermore, the acute kinetics of the changes of the extracellular to the intracellular fluid volumes as a function of fluid removal during hemodialysis treatment was investigated.The present study was conducted at the Division of Nephrology of the Centre for Child and Adolescent Medicine, University of Heidelberg, Germany, in cooperation with the Departments of Pediatric Nephrology at the University Hospitals of Cologne and Essen, Germany. One hundred and forty-one Caucasian outpatients, aged 1‑25 years, with chronic kidney failure participated in the present study. One hundred and twenty-eight children and adolescents were included in the analysis, while 13 were excluded, as no reliable bioimpedance measurements could be performed due to restlessness and agitation (9), spasticity (3), or an unphysiological result (1). The final cohort was composed of 22 patients on hemodialysis (HD), 21 treated with peritoneal dialysis (PD), 42 with a kidney transplant (TPL), and 43 suffering from chronic kidney disease without kidney replacement therapy (CKD). Subject characteristics are given in Tables The body composition monitor device (BCM), based on whole-body bioimpedance spectroscopy, is a tool to collect noninvasive information about body composition. The analyses were performed with the tetrapolar BCM device , using an alternating current from 50‑800 μA. Impedance was measured at 50 different frequencies between 5 kHz and 1 MHz and is composed of two parameters, resistance and reactance. The resistance  is inversely related to the content of tissue water, and the reactance , is directly related to the cell mass of tissue, i.e., cell wall capacitance , 13. To After lying down for at least 5 min, the BCM monitoring was performed on all CKD, PD, HD, and TPL patients in a supine position with arms and legs spread apart from the body in accordance with the manufacturer’s manual  , 16. Fout tests were applied. R2 is given when correlations were calculated. A p value of < 0.05 was considered to indicate significance.The median and range are given. The Kolmogorov-Smirnov test and the Shapiro-Wilk test were done to control for normal distribution of the values. For multiple comparisons, ANOVA and paired The patients were divided into four groups—patients with a kidney transplant (TPL), patients suffering from chronic kidney disease without kidney replacement therapy (CKD), patients on peritoneal dialysis (PD), and patients on hemodialysis treatment (HD) Figs. . Tables The hydration status was measured with the BCM. In HD patients, measurements were obtained before and after hemodialysis sessions. In addition, from the two measurements, the median value was calculated for each HD patient. In Fig. p < 0.001). These values declined in 21 of 22 subjects and remained unchanged in one patient during HD . Interestingly, considering the median values derived from the measurements before and after HD treatment, an equal distribution with a median value close to the zero reference line was observed   and intracellular (ICW) water per kilogram and the ratio of ECW/ICW was calculated Table . The medp < 0.001)  Table . The tim1) Table . As show1) Table ‑f. Secon1) Table . The patity Fig. .Fig. 3aThe BCM used to perform the present study is based on whole-body multi-frequency bioimpedance. This device is a versatile noninvasive tool for gaining immediate information about the composition of the body. Even though it is a practical device, it has some limitations. First, the patient must keep still for 5‑15 s, which can be difficult to achieve when young children are investigated. In the present study, nine patients had to be excluded from the analysis because they could not keep still for the time required. Eight of these patients belonged to the group of 18 children of our cohort aged 3 years or below. Second, the results of one girl younger than 1 year were removed despite a sufficient quality indicator value of the method, because the derived result appeared to be unphysiological. Based on the observation that most children studied with an age below 2 years did not provide reliable results, one cannot recommend the method for assessing fluid compartments in children below the age of two. Third, we observed a previously unreported specific entity excluding reliable measurements with the BCM. Two patients on peritoneal dialysis and one patient on hemodialysis suffered from severe spastic disease. Interestingly, it was not possible to obtain reliable results for impedance from the BCM, which displayed a quality of 0%. The mechanism for the absence of qualitatively acceptable results is unknown, but we hypothesize that patients with spasticity might have a too high resistance in the limbs causing incorrect current flow. Fourth, for measuring bioimpedance, the electrodes are placed on one arm and one leg. Thus, patients with amputations cannot be investigated since alternative placements of the electrodes have to be performed and assumptions for the model used for calculating total body bioimpedance have to be considered . In our The weakness of the present investigation is the absence of a healthy control group for direct comparison. In order to estimate whether the present results are physiologically meaningful, we compared our results with those obtained from studies using gold standard methodology for assessing body fluid compartments, i.e., heavy water and bromide dilution. Planche et al. assessed body fluid compartments in 17 children aged 1 to 10 years 28 days after recovering from malaria in Gabon . After rFigure During hemodialysis sessions, a substantial amount of fluid is removed from the body within a short time period. Thus, dialysis is an ideal experimental condition that allows testing the reliability of a novel method claiming to assess body fluid volumes. As shown in Fig. As a corollary, the ratio (ECW/kg)/(ICW/kg) declined steadily and reproducibly in all six patients observed on two occasions during hemodialysis treatment Fig. . The preThe present study confirms that BCM can be used for measuring fluid status by determining TBW, ECW, and ICW in children with chronic kidney failure with and without the various kidney replacement modalities. The results obtained by BCM compared well with those from the literature using isotope dilution. BCM enables assessing acute extracellular and intracellular fluid shifts, is intra-individually reproducible, causes no side effects, and is easy to apply. Future studies should define the clinical utility of the differential assessment of ECW and ICW.


Dear Sir,Journal of Clinical Hypertension.We read with great interest the paper entitled “Blood pressure variability and cognitive dysfunction: A systematic review and meta‐analysis of longitudinal cohort studies” recently published in the Parkinson's disease is also a very common cause of dementia that, together with Lewy body dementia  and multiple system atrophy (a progressive neurodegenerative disorder), constitute the so‐called synucleinopathies. These receive this name as abnormally misfolded α‐synuclein aggregates are a common finding in the peripheral and central nervous system of patients suffering from these conditions.Besides the cognitive impairment, the aforementioned pathologies characteristically share the existence of autonomic disturbances that cause both orthostatic hypotension and supine or nighttime hypertension leading to increased blood pressure variability.This topic is of special interest for us, since it is recently becoming more and more recognized that blood pressure variability influences on vascular events and ischemic diseases even over or independently to mean blood pressure values.After reading the review, we still have an unresolved question: Is blood pressure variability, due to its recognized capacity to cause vascular damage, the cause of dementia or, is dementia, which is sometimes associated with dysautonomia, the cause of the increased variability of blood pressure?We understand that both hypotheses could be true, but we do not understand how, according to the meta‐analysis results, blood pressure variability is related to all‐cause dementia but not individually with that of vascular origin or with other neurological causes of dementia, while considered separately. We would like to know the opinion about it from the authors.


To evaluate the effect of admission hyperglycemia on the short-term prognosis of patients with non-ST elevation acute coronary syndrome (NSTE-ACS) without diabetes mellitus.  The clinical data of 498 patients with NSTE-ACS admitted to the Department of Cardiology of the First Affiliated Hospital of Henan University of Science and Technology between March 2018 and November 2020 were analyzed. Based on the blood glucose (BG) level at admission, patients were divided into three groups: A (BG < 7.8 mmol/L), B (7.8 mmol/L ≤ BG < 11.1 mmol/L), and C (BG ≥ 11.1 mmol/L). The clinical data of the three groups were compared. p > 0.05). However, there were significant differences in the incidences of multivessel disease, renal insufficiency, pump failure, and emergency percutaneous coronary intervention, and levels of high-sensitivity C-reactive protein, cardiac troponin T, and creatine kinase isoenzyme MB among the three groups . The incidences of severe pump failure, malignant arrhythmias, and death were significantly higher in groups B and C compared to group A (p < 0.05). Additionally, the incidences of severe pump failure, malignant arrhythmias, and death were significantly higher in group C compared to group B (p < 0.05). Multivariate logistic regression analysis showed that hyperglycemia, renal insufficiency, Killip grade III/IV, and age were risk factors of in-hospital death.  There was no significant difference between the three groups in terms of age, sex, hypertension, hyperlipidemia, smoking, and history of myocardial infarction ( Hyperglycemia at admission is a risk factor for adverse in-hospital clinical outcomes in patients with NSTE-ACS. Diabetes is an important independent risk factor for coronary atherosclerosis. Many previous studies have confirmed that hyperglycemia at admission is common in patients with acute coronary syndrome (ACS), and it is a risk factor for in-hospital death and complications –4. PreviACS is a common, serious heart disease that comprises a group of syndromes due to rupture or invasion of the coronary atherosclerotic plaque and secondary complete or incomplete occlusive thrombosis. ACS includes acute ST-segment elevation myocardial infarction, acute non-ST-segment elevation myocardial infarction, and unstable angina (UA). The clinical classification of the acute coronary syndrome is shown in This was a retrospective analysis of prospectively enrolled consecutive NSTE-ACS patients treated at the Department of Cardiology of the First Affiliated Hospital of Henan University of Science and Technology from March 2018 to November 2020. NSTE-ACS was diagnosed on the basis of typical angina symptoms lasting for >10 minutes, accompanied by at least one of the following: ST-segment depression ≥ 0.5 mm, 0.5–1.0 mm transient ST-segment elevation in two consecutive leads for <30 minutes, T-wave inversion > 1 mm before the chest pain or within 12 hours after the chest pain, and/or myocardial enzymes (cardiac troponin T (TnT) or creatine kinase isozymes MB (CK-MB)) exceeding the upper limit of the normal values. Patients were excluded if they had past diabetes, incomplete clinical and coronary angiography data, admission BG level > 20 mmol/L, symptoms of ketoacidosis, and/or new-onset diabetes. A total of 498 patients with NSTE-ACS and high BG without history of diabetes were enrolled. The Ethical Committee of the First Affiliated Hospital of Henan University of Science and Technology approved the study protocol.Hypertension is a syndrome characterized by increased systemic arterial blood pressure (systolic pressure ≥ 140 mmHg and diastolic pressure ≥ 90 mmHg), which can be accompanied by functional or organ damage to the heart, brain, kidney, and/or other organs. Hypertension is the most common chronic disease and the main risk factor of cardiovascular and cerebrovascular diseases. Hypertension is divided into three grades according to severity: mild (systolic blood pressure: 140–159 mmHg or diastolic blood pressure: 90–99 mmHg), moderate (systolic blood pressure: 160–179 mmHg or diastolic blood pressure: 100–109 mmHg), and severe (systolic blood pressure: ≥180 mmHg or diastolic blood pressure: ≥110 mmHg).Hyperlipidemia refers to high blood lipid level, which can cause serious diseases, such as atherosclerosis, coronary heart disease, and pancreatitis. Hyperlipidemia usually is divided into hypertriglyceridemia, hypercholesterolemia, mixed hyperlipidemia, and low high-density lipoprotein cholesterol. Hypercholesterolemia is related to age and gender of patients. The majority of triglycerides are associated with genetic and environmental changes, and metabolic disorders. Most cases of hypertriglyceridemia are usually associated with abnormal BG, and diabetes mellitus is associated with hypertriglyceridemia.Heart failure refers to systolic and/or diastolic function of the heart, leading to impaired pumping of the blood returned from the venous circulation to the heart, causing blood stasis in the venous system, insufficient perfusion in the arterial system, and cardiac circulation disorder syndrome. This disorder manifests as pulmonary and vena cava congestion. Heart failure is not an independent disease, but the final stage of several heart diseases. The vast majority of cases of heart failure affect the left side of the heart, and the first manifestation is often pulmonary congestion. Severe pump failure is defined as New York Heart Association (NYHA) classification grade ≥ 3. Target lesion revascularization (TLR) is defined as repeated interventional therapy or bypass surgery within the stent and within 5 mm of the proximal and distal ends of the stent. Malignant arrhythmia includes ventricular tachycardia, ventricular fibrillation, and high atrioventricular block.Patients with suspected ACS underwent an electrocardiogram (ECG) and measurement of the BG level  and myocardial injury markers. ACS was classified by the cardiovascular doctor into unstable angina pectoris, acute ST-segment elevation myocardial infarction, and acute NSTE myocardial infarction based on the ECG and levels of myocardial injury markers. Emergency coronary angiography was performed on patients in a critical condition, such as intractable or recurrent angina pectoris with dynamic ST-segment changes, heart failure, life-threatening arrhythmia, or hemodynamic instability. Stents were implanted in these patients according to the disease condition after the target vessel was determined. Other patients in a less critical state underwent percutaneous coronary intervention (PCI). The research scheme of this paper is shown in n = 205), incomplete data (n = 24), BG level > 20 mmol/L (n = 12), symptoms of ketoacidosis (n = 8), or new-onset diabetes mellitus (n = 7). Finally, 498 NSTE-ACS patients were included in the study.After admission to the Department of Cardiology of the First Affiliated Hospital of Henan University of Science and Technology, the BG level of the patients was checked and ACS was classified into different types. We identified 754 NSTE-ACS with hyperglycemia but excluded 256 patients due to history of diabetes , B (7.8 mmol/L ≤ BG < 11.1 mmol/L), and C (BG ≥ 11.1 mmol/L). The risk factors for ACS were recorded for each group, including age, hypertension, hyperlipidemia, smoking history, clinical biochemical indexes, inflammatory markers, and left ventricular ejection fraction as measured by echocardiography. SPSS software  was used to perform statistical analysis. Differences were considered statistically significant at The quality of the statistical data affects the research accuracy. Data quality control requires scientific and rigorous work. In the context of big data, the quality and efficiency of hospital data should be continuously improved.All of the departments providing the data were incorporated into the information construction by our hospital to establish an ideal data quality management system. The hospital employees continuously regularly their skills and were familiar with the operation process of the information system. Our hospital regularly monitored the data operation and randomly checked the quality and standardization of the statistical to identify and solve potential problems. This ensured smooth information interaction in the hospital and improved the accuracy of the information. It also provided a solid foundation for the data quality control in our research.s is expressed asSPSS software  was used to perform statistical analysis. Continuous variables are represented by , Categorical variables are expressed as numbers or percentages. Means between the multiple groups were compared using one-way ANOVA. The chi-square test was used to measure the difference between the theoretical and actual values, using the following formula:χ2 represents the chi-square value, fo represents the actual value, and fe represents the theoretical value.In (2), Multivariate logistic stepwise regression was used to calculate the odds ratio (OR) for the predictors of in-hospital death and their impact on the outcomes.p > 0.05 for all). However, there were significant differences among the three groups in the incidences of the multivessel disease, renal insufficiency, Killip grade III/IV, and emergency PCI , as well as the levels of high-sensitivity C-reactive protein (hs-CRP), cardiac troponin T (TnT), and creatine kinase isoenzyme MB (CK-MB) . Comparison of the baseline characteristics of the three groups is shown in There was no significant difference among the three groups in terms of age, sex, hypertension, hyperlipidemia, smoking, and history of myocardial infarction (p < 0.05). The incidences of severe pump failure, malignant arrhythmia, and death were higher in group C than in group B (p < 0.05). Comparison of the in-hospital outcomes of the three groups is shown in The incidences of severe pump failure, malignant arrhythmia, and death were significantly higher in groups B and C than in group A  and von Willebrand factor. Acute hyperglycemia caused fibrinogen t1/2 to decrease and induced platelet aggregation, thereby increasing the levels of fibrinogen A, prothrombin, and factor VII levels. These changes indicate a prothrombotic state. Third, increased BG level was accompanied by increased vascular inflammatory markers [In vivo and in vitro studies showed that hyperglycemia was associated with increased hs-CRP, cytokine 26, and tumor necrosis factor α levels. In our study, hyperglycemia significantly correlated with increased inflammatory markers, which increased the incidence of adverse cardiac events through the inflammatory response. In addition, higher BG levels correlated with high levels of free fatty acids, greater insulin resistance, and more serious impairment of myocardial glucose utilization in ACS patients. This increased the oxygen consumption, potentially aggravating myocardial ischemia. At the same time, the increased levels of free fatty acids can induce malignant ventricular arrhythmia, which may be one reason for the increased occurrence of in-hospital cardiac arrhythmia with hyperglycemia [Second, hyperglycemia creates a prothrombotic state. In acutely hyperglycemic mice, the level of tissue plasminogen activator was decreased and the level of plasminogen activation inhibitor was increased. Hyperglycemia in type 2 diabetic patients  was associated with increased activity of thromboxane A markers , 24. In glycemia , 26.Therefore, hyperglycemia has different effects on the prognosis of patients with diabetes or undiagnosed diabetes. Hyperglycemia is more predictive of adverse events in patients with undiagnosed diabetes compared to those with diagnosed diabetes. Although the pathophysiological mechanism underlying this phenomenon is unknown, there are several explanations. Some undiagnosed diabetic patients, especially those with severe hyperglycemia, may be at high risk because they have never been treated for diabetes. In addition, in patients with unknown diabetes and hyperglycemia, when acute myocardial infarction occurs, even if blood glucose was significantly elevated, insulin therapy was rarely used. In view of the possible beneficial effect of insulin on myocardial ischemia, this difference in treatment may explain the different prognosis. Finally, it is possible that similar BG level may represent a more serious condition in unknown diabetic patients. There are still many gaps in understanding the relationship between hyperglycemia and the adverse prognosis. Further studies are needed to confirm whether hyperglycemia is an indicator of high mortality.Some limitations of this study should be considered. First, this is a single-center observational study with a small sample size. Second, in our analysis, intracoronary stenosis was determined on angiography, which may be affected by many factors. In the future, more reliable methods should be used to determine the intracoronary stenosis. Third, unmeasured residual confounding factors that may affect the evaluation of coronary stenosis may exist. Finally, the relatively small study population may theoretically lead to selection bias due to the strict inclusion and exclusion criteria. The conclusions drawn from our findings cannot be extrapolated to the patients excluded from the study.


There was a median (IQR) of 30.5% (26.2–34.4) reduction in body weight. Plasma glucose, glycosylated hemoglobin, fasting insulin and HOMA-index decreased at 3, 6 and 12 months of follow-up . The plasma aldosterone concentration (median (IQR)) also decreased at 12 months  to 65.4 , p = 0.003). Both leptin and hs-CRP decreased (p < 0.001) and adiponectine levels increased at 12 months post-BS (p = 0.017). Linear mixed-models showed that body weight  and plasma aldosterone  were the independent variables for changes in eGFR. Conversely, glycosylated hemoglobin was the only independent variable for changes in albuminuria . In conclusion, body weight and aldosterone are the main factors that mediate eGFR changes in obesity and BS, while albuminuria is associated with glucose homeostasis.Obesity-related hyperfiltration leads to an increased glomerular filtration rate (GFR) and hyperalbuminuria. These changes are reversible after bariatric surgery (BS). We aimed to explore obesity-related renal changes post-BS and to seek potential mechanisms. Sixty-two individuals with severe obesity were prospectively examined before and 3, 6 and 12 months post-BS. Anthropometric and laboratory data, 24 h-blood pressure, renin-angiotensin-aldosterone system (RAS) components, adipokines and inflammatory markers were determined. Both estimated GFR (eGFR) and albuminuria decreased from the baseline at all follow-up times ( Worldwide obesity has nearly tripled since 1975 . In addiHere we sought to assess changes in renal function at different follow-up times in patients with severe obesity undergoing BS. In addition, we explored the possible role of the renin-angiotensin aldosterone system (RAS), changes in glucose metabolism, and inflammation as potential mechanisms mediating these changes.2 or grade II obesity (BMI > 35 kg/m2) plus associated comorbidities . Patients with any endocrine disease causing obesity or severe psychiatric diseases were excluded. Detailed information on the trial was provided by qualified professionals of the Hypertension and Vascular Risk Unit . The exclusion criteria comprised the ruling out of the BS program for any reason or the refusal to give consent. The trial was approved by the local institutional Ethic Committee in accordance with the Declaration of Helsinki, and written informed consent was obtained from all participants.The BARIHTA study is a prospective observational trial in a cohort of consecutively enrolled patients with severe obesity scheduled to undergo BS . Details about BARIHTA trials have been previously published . Thus, tHere we evaluate and report the effects of BS on renal function and explore its possible mechanisms by analyzing its relationship with various components of the renin-angiotensin-aldosterone system (RAS), along with inflammatory markers and adipokines, as previously specified per protocol.Demographic, anthropometric and clinical data were recorded from all participants as a baseline. Anthropometric characteristics, pharmacological treatment, office- and 24 h-ambulatory-blood pressure (BP) recordings, routine laboratory tests, including renal function as assessed by the estimated glomerular filtration rate (eGFR) and by determining albuminuria, and determinations of components of the RAS, adipokines and inflammatory markers, were obtained at baseline and 1, 3, 6 and 12 months after surgery. Changes at follow-ups are evaluated from three months on to avoid the major hemodynamic instability one month after BS. Hypertension was considered if previously diagnosed and/or if the baseline 24 h-BP was ≥130/80 mmHg. Diabetes mellitus (DM) was considered if the patient received antidiabetic treatment or had ≥2 fasting plasma glucose determinations ≥126 mg/dL or if glycosylated haemoglobin A1c was >6.5%.About one-third of the study population was under treatment with at least one drug that interfered with the RAS. Given that these drugs could introduce a bias by interfering with renal function parameters, the main analyzes were performed separately in both the entire cohort and in the untreated patients.® NG-ambulatory blood pressure (NG-ABPM) device by IEM, Stolberg, Germany. The monitor was placed on a working day between 08:00–10:00 h A.M., and after a 5 min rest, BP was consecutively determined four times at 1-min intervals. The mean was established as office BP. Brachial artery waveforms were then automatically recorded at 20-min intervals. Suitably sized cuffs were used according to the arm circumference measured in each study visit. All patients had recordings of good technical quality . If not, a new ambulatory-BP-monitoring (ABPM) was repeated within 1 week.Brachial-BP measurements and calculation of central-BP and other arterial parameters through the oscillometric method  were obtained from a Mobil-O-GraphUrinary Albumin ExcretionUrinary albumin excretion  was determined before BS and at the determined follow-up time-points and measured as the average of urinary albumin/creatinine ratio (ACR) from 2 fresh first-morning-void urine samples obtained on separate days. Microalbuminuria was defined as an ACR ≥ 30 mg/g. Serum Creatinine and eGFRSerum creatinine (SCr) was measured by an enzymatic modified Jaffe reaction  using the Hitachi Modular System Analyzer (Roche Diagnostics), consistent with the current National Kidney Disease Education Program recommendations for standardizing SCr measurement . The intThere is no current agreement as to the best method to estimate the GFR in individuals with severe obesity. However, in a recently reported study , the modRenin-Angiotensin-Aldosterone System (RAAS) ComponentsPlasma renin activity (PRA) and plasma aldosterone concentration, as well as angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme-2 (ACE2) activities, were measured by validated laboratory methods . DetailsAdipokines and Inflammatory ParametersLeptin, adiponectin, and other cytokines and inflammatory markers, e.g., resistin, angiopoietin-2, MCP-1 and high-sensitivity C-reactive protein (hs-CRP), were also determined. See 2, as a first-step treatment in cases with a body mass index (BMI) > 50 kg/m2 and when drug malabsorption was to be avoided [Either laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) were performed, and any of these two were chosen for each patient based on clinical criteria and the consensus of the Bariatric Surgery Unit. In this line, LSG was preferred in younger patients, in those with a BMI ranging from 35–40 kg/m avoided . The LRYp-value. A change was considered significant if the two-side alpha level was ≤0.05. We used the statistical package SPSS for Windows version 25.0 , and STATA package version 15 , for statistical analysis.Elementary statistical methods were applied with statistical package SPSS for Windows version 25.0 . The normality assumption for continuous variables was tested through the Kolmogorov–Smirnov test. Variables fulfilling this normality assumption were summarized as the mean ± S.D. or the median  otherwise. Categorical data were presented as frequencies and percentages. Comparisons of analyzed variables between two observed periods were carried out by paired t tests or Wilcoxon signed rank tests. Pearson or Spearman correlation coefficients were used for testing bivariate correlations as appropriate. Separate linear mixed-models were built for both the variation of eGFR-CG and the variation of albuminuria. All variables which deviate from the normal distribution were log-transformed (ln) before being introduced into the model. In these models, data were expressed as regression coefficient, 95% confidence interval (95% CI) and About one-third of the study population received treatment with one or more drugs that interfered with RAS. Given that these drugs could introduce a bias by interfering with renal function parameters, the main analyses were performed separately in both the entire cohort and in the untreated patients.2, before BS. None of the patients had chronic kidney disease based on the estimated glomerular filtration rate, nor did any of them die at follow-up.Sixty-two patients completed the BARIHTA study, and information on renal changes was available for all of them at the baseline and follow-ups. A flowchart is supplied . Baselin2 (p < 0.001), reflecting the hyperfiltration that characterizes patients with severe obesity. In addition, the albuminuria, as measured by the log-transformed albumin-creatinine ratio (lnACR), decreased from 1.85 ± 1.08 to 1.56 ± 0.73 (p = 0.056). Both the estimated GFR (p for trend <0.001 for both). The estimated GFR decreased from 155.9 ± 36.3 to 127.7 ± 27.4 mL/min/1.73 mated GFR A and theated GFR B experie2 at baseline and 29.7 ± 4.8 kg/m2 one year after BS (p < 0.001). p < 0.001). A waist circumference (cm) decrease was confirmed in both men (140.2 ± 14.3 vs. 111.4 ± 16.3) and women (129.8 ± 10.1 vs. 103.4 ± 11.7), (p < 0.001 for both comparisons). Overall, there was a median (IQR) 30.5% (26.2–34.4) reduction in body weight 12 months after BS. Body mass index was 42.7 ± 5.6 kg/mp = 0.01 after adjustment for age and sex.As previously reported , office p = 0.001) and waist circumference .There was a statistically significant correlation between the variation at 12 months of peripheral 24-h systolic blood pressure (SBP) and the variation of both body weight .p for trend < 0.001 for all).The changes at 12 months after BS in various components of the RAS were also assessed. As expected, there was a statistically significant decrease in plasma renin activity and aldosterone plasma concentration, as well as an increase in the ACEactivity/ACE2 activity ratio after BS see . These cThere were statistically significant changes 12 months after BS in the explored adipokines and inflammatory markers . As seenSeparate mixed-models were built for both the variation of eGFR-CG and the variation of albuminuria . The tesThe models with a better performance show that the statistically significant independent variables for eGFR A were boThe main finding of this study is that in obese patients undergoing BS the mechanisms by which the estimated glomerular filtration rate and albuminuria return to normal values are possibly different. Thus, we demonstrate that normalization of eGFR is associated with a decrease in both body weight and plasma aldosterone concentration, while a decrease in albuminuria is directly correlated with an improvement in glucose metabolism.Weight excess is associated with an altered renal haemodynamic profile, i.e., an increased GFR relative to effective renal plasma flow, resulting in an increased filtration fraction . HyperfiSeveral studies have investigated the mechanisms likely to be responsible for renal changes observed in obese patients. A large number of these studies refer to hyperfiltration in general terms, focusing mainly on eGFR, especially with regard to the consequences of BS on renal function. Some of them found a relationship between the decrease in eGFR after BS and an improvement in the toxic adipokine profile observed in these patients ,9. In ouThe second relevant finding of this study is the close relationship between decreased albuminuria and improvement in all parameters of glucose metabolism. Indeed, most of the reported investigations regarding decreases in albuminuria after BS are based on cohorts of diabetic patients ,26,27,28We need to point out some limitations of the study. First, the GFR was estimated rather than measured directly. However, it should be noted that we determined the eGFR at various points over the 12 months and observed a significant decrease at any given time. In addition, although it has been suggested that weight loss-related changes in muscle mass influence eGFR to some extent, it is unlikely that a gradual decrease in eGFR over 12 months of follow-up will be accompanied by a continued decrease in muscle mass during this time. Second, for technical reasons, we were unable to determine interleukin-6 in most samples, so these data were excluded from the final analyses. Although it is a well-known marker of inflammation, we have complete data on hs-CRP, another hallmark of inflammation, and it was finally rejected that it played an important role in renal changes after adjustment for other variables. Finally, we cannot ignore the fact that the possible role of the RAS in changes in eGFR and glucose metabolism in changes in albuminuria are only hypotheses that should be confirmed in a randomized clinical trial.In conclusion, our study demonstrates that weight loss and especially decreased aldosterone levels are the main factors associated to the restoration of the abnormally increased eGFR seen in obese patients after BS. This highlights the importance of the possible role of the RAS in renal hemodynamic alterations in obese patients that ultimately impair renal function. On the other hand, we show that increased albuminuria in obese patients is related to impaired glucose metabolism, regardless of blood pressure and weight loss.


To evaluate the effects of variations in systolic blood pressure (SBP) and pulse pressure (PP) on diabetic retinopathy (DR) in patients with type 2 diabetes.  A total of 3275 type 2 diabetes patients without DR at Taiwan Lee's United Clinic from 2002 to 2014 were enrolled in the study. The average age of the patients was 65.5 (±12.2) years, and the follow-up period ranged from 3 to 10 years. Blood pressure variability was defined as the standard deviation (SD) of the average blood pressure values over the entire study period and was calculated for each patient. The mean SD for SBP was 11.16, and a SBP ≥ 130 mmHg (1 mmHg = 0.133 kPa) was defined as high SBP. Based on these data, patients were divided into four groups as follows: group 1 , group 2 , group 3 , and group 4 . Based on a mean PP of 80 mmHg with a pulse pressure SD of 6.53 mmHg, the patients were regrouped into four groups designated G1′-G4′. P < 0.01) and patients in the G1 group had the lowest risk. Patients in the G3 group  had a higher risk of DR compared to those in the G2 group . After the restratification of patients based on the mean and SD of the pulse pressures, it was found that patients in the G2′ group had the highest risk of DR , whilst patients in the G1′ group had the lowest risk. Also, the risk of DR in the G4′ group  was higher than that in the G3′ group .  After adjusting for patient age, sex, and disease course, Cox regression showed that the mean and SD of SBP, pulse pressure, and their SDs were risk factors for DR. After stratifying the patients based on the mean and SD of the SBP, we found that the patients in the G4 group had the highest risk of DR (hazard ratio (HR) = 1.980, 95% CI: 1.716~2.285,  Variability in SBP and PP are risk factors for DR in patients with type 2 diabetes. The variability of PP was better able to predict the occurrence of DR than mean pulse pressure. Blood pressure variability (BPV), also known as blood pressure fluctuation, refers to the degree of fluctuation in blood pressure within a certain time. Quantification of BPV usually uses the SD of blood pressure readings measured over a certain time to indicate the degree of overall changes in blood pressure during that period. BPV is often independent of the average blood pressure levels and is closely related to cardiovascular and cerebrovascular damage in diabetes patients where high variability indicates cardiovascular and cerebrovascular damage , 2.Diabetic retinopathy (DR) is a common microvascular complication and an important cause of vision damage and blindness in diabetes patients –5. Hypern = 557), those with blood pressure measurements taken fewer than three times per year (n = 402), those with missing or incomplete data (n = 1378), and those who did not have T2DM (n = 428) were excluded from the study. Finally, 3275 patients without DR at baseline were included in the study. This study was approved by the Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University and the Taiwan Lee's United Clinic, China (19-053-B). All participants recruited to the study provided written informed consent.This was a prospective cohort study. Diabetes patients who visited Taiwan Lee's United Clinics from 1 January 2002 to 30 December 2014 were enrolled in the study. Patients were followed up for 3 to 10 years, with patients requested to have four follow-up visits per year. If a patient did not come for the visit as scheduled, the health care professionals would remind the patient to come to the clinics. Patients with a follow-up period less than 3 years (Data were collected from the database including the following: (1) demographic and clinical data, including age, sex, diabetes course, smoking, drinking, exercise habits, medication , height, weight, waist circumference, hip circumference, body mass index (BMI), waist-to-hip ratio, systolic pressure, diastolic pressure, and pulse pressure, and (2) laboratory data, including fasting blood that was collected every quarter (after fasting overnight for more than 8 hours). High-performance liquid chromatography  was used to measure glycated hemoglobin A1c (HbA1c). A Roche Cobas600 automatic biochemical analyzer was used to measure the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). (3) Direct ophthalmoscopy after mydriasis was performed by an ophthalmologist. The presence of microaneurysm, cotton wool spots, intracavitary microvascular abnormalities, bleeding, hard exudate, venous aneurysm, or new retinal blood vessels was defined as DR . During Blood pressure values with a systolic pressure in the range of 50-300 mmHg (1 mmHg = 0.133 kPa), diastolic pressure in the range of 30-180 mmHg, and PP in the range of 20-120 mmHg were recognized as effective measurement values . The mean = 3275) were divided into four groups as follows: G1 , G2 , G3 , and G4 . Based on a mean PP of 80 mmHg and a SD of the PP of 6.53 mmHg, the 3275 patients were regrouped into four groups designated G1′-G4′: G1′ , G2′ , G3′ , and G4′ .A mean SD of SBP of 11.16, and a SBP ≥ 130 mmHg (1 mmHg = 0.133 kPa) were defined as high SBP. Based on these data, all the patients , and a nonparametric test was used for intergroup comparisons. Cox regression analysis was used to analyze the relationship between different blood pressure variables and the development of DR. As we grouped patients into G1-G4 according to their SPB and SD of SBP and G1′-G4′ according to their PP and SD of PP to compare between the different groups, G1 and G1′ served as the reference in the COX regression models. Covariates including age, sex, course of the disease, BMI, waist-to-hip ratio, HbA1c, TC, TG, LDL-C, and HDL-C were entered into the models simultaneously. Hazard ratios (HR) and their respective 95% confidence intervals (CI) were calculated. P values of <0.05 were considered statistically significant.SPSS 22.0 software was used for statistical analysis. Count data were expressed as the number of cases (%), and a P > 0.05). Compared to the NDR group, patients in the DR group were older, had had a longer duration of diabetes, and had poorer exercise habits. They also had a higher incidence of macular edema and cataracts, lower use of hypoglycemic drugs and insulin, and higher levels of HbA1c, SBP, and pulse pressure. The NDR patients also had lower levels of HDL-C. The differences between the groups were all statistically significant  group (2833 cases) and a DR group (442 cases) in which 100 cases had nonproliferative DR and 342 cases had proliferative DR. Among the patients with proliferative DR, 247 cases were at the early stage of proliferation, 72 cases were at the fibrotic stage, and 23 cases were at the late stage of proliferation. During follow-up, progression of DR was observed, with 15 patients progressing from nonproliferative to proliferative DR and being in the early stage of proliferation. Thirteen cases progressed from the early proliferative stage to the fibrotic stage, and three patients progressed from the fibrotic stage to the late stage of proliferation. There were no significant differences in sex, BMI, waist-to-hip ratio, smoking history, drinking history, use of lipid-lowering drugs, use of antihypertensive drugs, diastolic blood pressure, MAP, TC, TG, and LDL-C between the NDR and the DR groups (P < 0.01), SD of SBP , mean PP , SD , HbA1c , higher LDL-C , and lower HDL-C  were associated with more rapid development of DR  = 1.023, 95% confidence interval (CI): 1.019~1.028, nt of DR .P < 0.01) and patients in the G1 group had the lowest risk. Also, patients in the G3 group  had a higher risk of DR compared to those in the G2 group  and patients in the G1′ group had the lowest risk. Also, patients in the G4′ group  had a higher risk of DR compared to those in the G3′ group , G2′ , G3′ , and G4′ . After adjusting for age, sex, disease course, BMI, waist-to-hip ratio, HbA1c, TC, TG, LDL-C, and HDL-C, Cox regression analysis showed that patients in the G2′ group had the highest risk of DR (HR = 2.086, 95% CI: 1.641~2.652, Compared to the other three groups, patients in the G4 group had the highest risk of DR. The risk of DR increased between our study groups when the mean systolic pressure exceeded 130 mmHg, the SD of SBP exceeded 8 mmHg, the mean PP exceeded 70 mmHg, and the SD of PP exceeded 4 mmHg .Studies have shown , 15 thatAlthough it is currently unclear how SBP and PP affect DR in T2DM patients, it can be hypothesized that increased blood pressure may damage retinal capillary endothelial cells . StudiesDiastolic blood pressure is an important blood pressure parameter. In this study, no correlation was found between diastolic blood pressure and DR in T2DM patients which is consistent with the results from Kawasaki et al.  and RudnThe variability in SBP and PP is more harmful to DR than the average SBP and pulse pressure. In clinical practice, physicians should avoid drastically lowering the blood pressure of patients over a short time. This is particularly important in China where the insurance strategy for inpatients is better than that for outpatients. Many hypertensive patients prefer to be hospitalized. Reducing the blood pressure from a relatively high level to a near-normal level within an average time of seven days of hospitalization will inevitably lead to an increase in BPV. These changes affect the occurrence of chronic microvascular complications such as DR. Our data support the development of individualized blood pressure reduction programs to smoothly lower blood pressure and reduce BPV.Our study has several advantages in that it was performed as a large prospective longitudinal cohort study with a sufficient sample size. Each patient was followed up for at least three years with an average follow-up time of seven years. Also, at least three independent systolic and PP measurements were used to calculate the mean systolic and pulse pressures, as well as the variability in the systolic and pulse pressures. These data provided reliable parameters for the mean systolic and PP as well as the variability of systolic and pulse pressure. One of the main limitations of this study was that during the follow-up period, the number and intervals of systolic and PP measurements varied for each subject per year even though they were supposed to be measured every quarter. Also, as our data were only collected from patients with DR, we are not able to determine if the DR was caused by hypertension or by diabetes. No further analysis of the data was performed to focus specifically on hypertensive DR.In conclusion, variability in SBP and PP are risk factors for DR in patients with T2DM. This variability may be more important than the mean SBP and PP in the development of DR. In the future, individualized blood pressure reduction programs should be considered in clinical practice to slowly lower blood pressure and improve BPV, thereby delaying the risk of chronic complications of diabetes such as DR.


Sodium–glucose co-transport 2 inhibitors (SGLT2i) lower blood pressure (BP) in normotensive subjects and in hypertensive and normotensive diabetic and non-diabetic patients. However, the mechanisms of these BP changes are not fully understood. Therefore, we examined the clinical and biochemical determinants of the BP response to empagliflozin based on 24-h ambulatory BP monitoring.post-hoc analysis of a double-blind, randomized, placebo-controlled study examining the renal effects of empagliflozin 10 mg vs. placebo in untreated normotensive non-diabetic subjects, the 1-month changes in 24 h ambulatory BP were analyzed in 39 subjects (13 placebo/26 empagliflozin) in regard to changes in biochemical and hormonal parameters.In this p < 0.001) and −2 ± 6 mmHg (p = 0.03). The effect on SBP and DBP was more pronounced during nighttime . The main determinants of daytime and nighttime SBP and DBP responses were baseline BP levels . Although empaglifozin induced significant biochemical changes, none correlated with blood pressure changes including urinary sodium, lithium, glucose and urate excretion and free water clearance. Plasma renin activity and plasma aldosterone levels increased significantly at 1 month suggesting plasma volume contraction, while plasma metanephrine and copeptin levels remained the same. Renal resistive indexes did not change with empagliflozin.At 1 month, empagliflozin 10 mg decreased 24-h systolic (SBP) and diastolic (DBP) BP significantly by −5 ± 7 mmHg (SGLT2 inhibition lowers daytime and nighttime ambulatory systolic and diastolic BP in normotensive non-diabetic subjects. Twenty-four jour changes are pronounced and comparable to those described in diabetic or hypertensive subjects. Baseline ambulatory BP was the only identified determinant of systolic and diastolic BP response. This suggests that still other factors than sustained glycosuria or proximal sodium excretion may contribute to the resetting to lower blood pressure levels with SGLT2 inhibition.https://www.clinicaltrials.gov], identifier [NCT03093103].[ In the development program of all sodium–glucose co-transport 2 inhibitors (SGLT2i), significant reductions in blood pressure (BP) were observed in normotensive subjects as well as in hypertensive and normotensive diabetic patients , 2. Thuspost-hoc analysis, we examine the clinical and biochemical determinants of the BP response to empagliflozin based on the 24 h, diurnal, and nocturnal ambulatory BP values.We investigated recently the acute and sustained effects of empagliflozin on renal tissue oxygenation and BP in normotensive non-diabetic subjects . In thisDetails of the study protocol have been previously published , 5. In b2, a urine albumin/creatinine ratio < 3.3 mg/mmol, a normal urine dipstick, normal hematology and chemistry results and a normal renal ultrasound. Each group was randomized to placebo (n = 15) or empagliflozin (n = 30). The randomization procedure was done by the hospital pharmacy. A 2:1 randomization was chosen to compensate the possible higher drop-out rate in the empagliflozin group due to side effects. Empagliflozin 10 mg or placebo pills were identical in size and stored in similar boxes containing 30 pills. Investigators  were blinded to treatment.An announcement for recruitment was posted at the University Hospital Center (CHUV) in Lausanne, which was visible on the web page of the institution. After contacting the study nurse, volunteers received an information sheet which included detailed information on the study protocol, side effects, their symptoms, treatment, and preventive measures, and they were invited to an information visit. Then, a minimum of 48 h was requested before confirming their interest and planning the screening visit. Inclusion criteria included the absence of diabetes (HbA1C < 6.5%) and a normal oral glucose tolerance test , a CKD-EPI based eGFR > 60 ml/min/1.73 mAt baseline, each subject underwent a 24 h ambulatory BP (ABPM) recording using a validated device  and a 24 h urine collection without any treatment. Blood pressure was measured every 20 min during daytime and every 30 min during nighttime. To be validated, the 24 h ABPM had to have a minimum of 20 measurements during daytime and 7 measurements during nighttime .A renal ultrasound was performed using an Aplio XG device . The renal resistive indexes were measured on three segmental arteries  in each kidney and averaged. Volunteers were instructed not to smoke or drink alcohol or have any caffeine-containing beverage during study days. On the following morning, after a light breakfast at 7am, the volunteer arrived at the study center at 9am. Blood samples were collected before the administration of the first dose of placebo or empagliflozin 10 mg. Volunteers left the center and continued taking the pill once a day in the morning for 4 weeks. During this period, they were examined once a week and had a telephone call on another day each week for safety reasons. On the day before the last pill, the 24 h ABPM and 24 h urine collection were repeated with blood sampling on the next day.® . Plasma and urine osmolality were measured by flame photometry. Proximal renal sodium handling was assessed by the determination of fractional excretion of endogeneous lithium (FELi), a proxy of proximal sodium reabsorption as described previously (H2O) = Urinary volume – Osmolar clearance.Plasma and urine samples were analyzed for glucose, urea nitrogen, creatinine, bicarbonate, urate and sodium, using routine clinical chemistry methods on a Cobas 8000eviously . The fraPlasma renin activity (PRA) was measured using a radioimmunoassay commercial kit for the quantitative determination of Angiotensin I in human plasma, while aldosterone quantification in blood was performed with the Aldo-Riact RIA kit . Plasma metanephrines and normetanephrines were measured by ultra-high pressure liquid chromatography-tandem mass spectrometry . Copeptipost-hoc analyses, we investigated the determinants of a predefined secondary outcome, i.e., the empagliflozin-induced effects on 24 h ambulatory BP with a separate analysis for diurnal and nocturnal BP.The primary outcome of this study was the acute and chronic effects of empagliflozin on renal tissue oxygenation as measured by blood-oxygen-level-dependent magnetic resonance imaging (BOLD-MRI) and results have been published recently . In this–1) with a sigma (standard deviation) of 5% (1 s–1). This estimation and SD were partly based on our previous studies as detailed previously  or empagliflozin 10 mg once daily (n = 30). For analysis, we considered only subjects who completed the full protocol (acute + chronic phases). Hence, the BP data of 13 subjects of the placebo group and 26 subjects of the empagliflozin group were analyzed . When compared to placebo, 24 h ambulatory BP measurements showed significant decreases in systolic  and diastolic BP  with empagliflozin (p = 0.004) than during the day  (p = 0.006. Variability of systolic blood pressure was defined by the standard deviation of systolic blood pressure (SD). Diurnal and nocturnal variabilities remained the same at 1 month with placebo, resp: −1.0 ± 6.5 mmHg; + 1.2 ± 5.3 mmHg. Diurnal variability decreased with empagliflozin  but nocturnal variability remained the same . No subject developed symptoms of orthostatic hypotension. Nocturnal diastolic BP decreased significantly with empagliflozin  while the effect on diurnal diastolic BP was only mild. Diurnal and nocturnal heart rate remained unchanged.Weight, office systolic and diastolic BP and heart rate were unchanged after 1-month of placebo . Weight liflozin . The eff = 0.01) , 2. The p < 0.0001) with an increase in urinary urate excretion both during the day and the night (Δ daytime FEurate + 3.2 ± 2.1% (p < 0.0001) and Δ nighttime FEurate + 3.6 ± 1.9% (p < 0.0001)]. During the night, free water clearance decreased with empagliflozin in comparison to placebo.The changes in blood and urinary parameters are shown in p = 0.02). The fractional excretion of lithium was slightly higher during daytime under empagliflozin  but comparable during nighttime.Regarding electrolytes, sodium excretion was not increased during daytime with empagliflozin but during the night, sodium excretion was significantly lower after 1 month of empagliflozin  as well as plasma renin activity . Plasma normetanephrine and metanephrine levels were not affected by the administration of empagliflozin. Plasma copeptin levels increased mildly but not significantly with empagliflozin.Plasma aldosterone levels increased significantly after 1 month of empagliflozin  at baseline and at 4 weeks.p = 0.0007) and the night . The correlations were significant but weaker with baseline DBP . The acute and 1-month changes in daytime glycosuria did not correlate with the acute or sustained changes in daytime ambulatory BP (data not shown for acute). Likewise, the 1 month changes in nighttime glycosuria did not correlate with the sustained changes in nighttime ambulatory BP. Neither urinary sodium, lithium excretion nor changes in plasma uric acid or uric acid urinary excretion or changes in free water clearance correlated with the sustained changes in BP.Linear regression analyses in subjects receiving empagliflozin showed a correlation between baseline systolic BP and BP response to empagliflozin during the day  even after correction for glycosuria (p = 0.02). Changes in nighttime DBP correlated significantly with changes in plasma PRA levels .The changes in nighttime SBP at week 4 correlated significantly with the changes in plasma aldosterone levels . Diurnal and nocturnal glycosuria correlated with diurnal and nocturnal uricosuria .Changes in nocturnal glycosuria measured at 4 week correlated with the changes in plasma aldosterone  in patients with type 2 diabetes with or without hypertension –11. In tMore relevant is the impact of SGLT2 inhibition on 24 h ambulatory BP control with a stronger effect during the night. In patients with hypertension and type 2 diabetes, empagliflozin lowered ambulatory systolic and diastolic BP by 4 and 3 mmHg, respectively and independently from baseline antihypertensive therapy . This obAs reported previously, the decrease in BP was not accompanied by any increase in heart rate. This observation has been attributed to a sympatho-inhibitory effect of SGLT2 inhibitors . Thus, nThe link between SGLT2 inhibition and the decrease in BP is generally attributed to the glycosuria leading to osmotic diuresis and hence an increase in urinary sodium and volume excretion. In our initial paper , we did In the present analysis, the decrease in systolic and diastolic ambulatory BP at 1 month correlated with baseline BP. Neither diurnal nor nocturnal sodium excretion, uricosuria or glycosuria were associated with the reduction in BP. Although fractional excretion of lithium increased, it did not correlate with blood pressure changes. One of the reasons why we did not find any association between urinary sodium excretion and BP changes might be the small number of subjects studied or the fact that a standardized diet was not prescribed. Alternatively, this may indicate that still other mechanisms are involved. Thus, it is interesting to note that SGLT2 inhibitors lower BP in patients with CKD despite a blunted effect on glycosuria and urinary sodium excretion suggesting some dissociation of the natriuretic effect and BP responses to SGLT2 inhibitors. Of note, diurnal and nocturnal glycosuria was associated with uricosuria suggesting either the impact of a high proximal flow rate, the activation of GLUT9 or the inhibition of URAT1 due to glycosuria as recently hypothesized . As for Limitations of the study: the likelihood of identifying the biological or hormonal determinants of blood pressure response was weakened by the small number of subjects and the absence of a standardized diet.Perspectives: SGLT2 inhibition decreases blood pressure in normotension and particularly in normal high blood pressure subjects. There may be an interest to further explore whether SGLT2 inhibition has additional benefits to non-pharmacological therapy as diet and exercise in individuals with normal high blood pressure.Taken together our results confirm a significant reduction of daytime and nighttime ambulatory BP after 1 month of empagliflozin in normotensive non-diabetic subjects. Twenty-four hour changes are pronounced and comparable to those described in diabetic or hypertensive subjects. Empagliflozin induced expected changes in hematocrit and urinary glucose, sodium and uric acid excretion. However, baseline ambulatory SBP and DBP were the only identified determinants of systolic and diastolic BP response. Although a transient increase in urinary sodium excretion could also contribute to lower BP in our subjects as well as in patients, we were not able to demonstrate that the natriuretic response to empagliflozin was a key determinant of the SGLT2-induced decrease in BP at 1 month. This may suggest that still additional factors such as changes in baroreceptor activity or cardiac function might contribute to the beneficial effects of SGLT2 inhibitors on blood pressure.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics committee of the Canton de Vaud, Switzerland. The patients/participants provided their written informed consent to participate in this study.MB is the principal investigator. AZ wrote the study protocol and co-investigator and the corresponding author. M-EM and AG-W is responsible for the running of the clinical trial and is co-investigator. MP, GW, and OB are co-investigators. All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


While there is a strong association between adhering to a healthy dietary pattern and reductions in blood pressure, adherence remains low. New technologies aimed to help facilitate behavior change may have an effect on reducing blood pressure among individuals with hypertension.This study aims to evaluate characteristics of participants with stage 2 hypertension who used Foodsmart and to assess changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP).We analyzed demographic, dietary, and clinical characteristics collected from 11,934 adults with at least two blood pressure readings who used the Foodsmart platform. Stage 2 hypertension was defined as SBP ≥140 mmHg or DBP ≥90 mmHg. We calculated mean changes in blood pressure among participants with stage 2 hypertension and stratified by length of follow-up and the covariates associated with achieving blood pressure levels below stage 2 hypertension. We compared changes in diet quality and weight between participants with stage 2 hypertension at baseline who achieved stage 1 hypertension or below and those who did not.P=.001) and weight (P=.04) were statistically significantly associated with changes in blood pressure categories for users with stage 2 hypertension at baseline. Using a multivariable logistic regression model, we found that baseline Nutriscore, change in Nutriscore, and change in weight were associated with greater likelihood of users with stage 2 hypertension at baseline achieving a lower blood pressure category.We found that 10.63%  of participants had stage 2 hypertension at baseline. Among Foodsmart participants with stage 2 hypertension at baseline, SBP and DBP decreased, on average, by 5.7 and 4.0 mmHg, respectively; 33.02% (419/1269) of participants with stage 2 hypertension at baseline achieved blood pressure levels below stage 2 hypertension (SBP <140 mmHg and DBP <90 mmHg). Using a multivariable ordinal logistic regression model, changes in Nutriscore  of the Foodsmart platform and found that those with stage 2 hypertension, on average, improved their blood pressure levels over time. Almost half of all adults living in the United States have hypertension, with only 1 in 4 having their condition under control . UncontrA healthy diet is an important part of an individual’s toolkit to reduce their blood pressure. Previous studies have shown that a healthy dietary pattern can reduce hypertension to controlled levels. For example, the Dietary Approaches to Stop Hypertension (DASH) diet is composed of fruits, vegetables, and low-fat dairy products. Filippou et al  found inFoodsmart, a digital nutrition platform, is a potential solution to address these barriers. The platform helps its users improve their health by providing them information about their current diet and pinpointing areas of improvement, while also providing personalized recipes and meal planning options to achieve target goals. The platform also assists in purchasing healthier foods with direct integration from meal plans to grocery lists to retailers through an ad-free environment. Consequently, Foodsmart is able to create sustainable behavior change for its users by making the process easy, quick, and affordable. Previous research has shown that this sustained behavior change has resulted in sustained changes in biometrics as well. Hu et al  found thPrevious studies have also shown the effectiveness of digital nutrition interventions in helping participants lower their blood pressure. Milani et al  providedThis study aims to characterize Foodsmart participants with stage 2 hypertension, as well as identify what characteristics are associated with returning to stage 1 hypertension levels or lower among those with stage 2 hypertension. It also aims to evaluate changes in blood pressure levels and other biometrics over time among participants with hypertension.As of August 2021, 106,816 participants of Foodsmart who were older than 18 years living the United States and enrolled since January 2016 had entered plausible systolic and diastolic readings . Of those Foodsmart participants, 11,934 had reported at least two systolic/diastolic readings, with the first and last reported readings at least 30 days apart. Our final sample size was 11,934 participants with at least two reports of SBP and DBP.Foodsmart is a digital nutrition platform that facilitates sustained dietary and behavior change through 2 main components, FoodSmart and FoodsMart. Foodsmart has been described previously . In brieFoodsmart is available through health plans and employers and can be accessed via the web or the iOS or Android operating system.2 or ≥50 kg/m2. Length of follow-up was calculated as the number of days between the first and last systolic/diastolic measures inputted. We defined normotension as SBP <120 mmHg and DBP <80 mmHg, elevated blood pressure as SBP between 120 and 129 mmHg (inclusive) and DBP <80, stage 1 hypertension as either SBP between 130 and 139 mmHg (inclusive) or DBP between 80-89 mmHg (inclusive), and stage 2 hypertension as either SBP ≥140 mmHg or DBP ≥90 mmHg, as defined by the American Heart Association [Foodsmart participants were able to input their biometrics such as blood pressure, height, and weight, and were able to report new biometrics at any time. Because of potential errors in participants self-reporting their biometrics, the following values were considered as outliers and removed: SBP ≤80 mmHg or ≥300 mmHg, DBP ≤40 mmHg or ≥200 mmHg, weight ≤27.2 kg or ≥181.1 kg, and BMI ≤15 kg/mociation . These r2). Participants’ baseline BMI was categorized as normal BMI (BMI <25 kg/m2), overweight (25-29.9 kg/m2), or obese (BMI ≥30 kg/m2). Participants were also able to report any conditions they currently had  in the Nutriquiz.Baseline BMI was calculated as the baseline weight entered in kilograms divided by height in meters squared  when they sign up . DemograBased on responses from the Nutriquiz and the daily dietary intake, a score (Nutriscore) from 0 to 70 was calculated to assess overall diet quality, with 70 being the highest diet quality. The Nutriscore is based on the Alternative Healthy Eating Index-2010 and the Commonwealth Scientific and Industrial Research Organization Healthy Diet Score ,14. Chant tests (unpaired) to evaluate differences in continuous variables.We performed exploratory data analyses to assess the baseline demographic characteristics, SBP and DBP levels, and diet quality of the total study population, stratified by whether participants had stage 2 hypertension at baseline or not. We reported categorical variables as number of participants (percentage of study population) and continuous variables as mean (SD). We used chi-square tests to assess whether categorical variables are independent of baseline stage 2 hypertension status, and 2-sample Univariate and multivariable ordinal logistic regression analyses were used to estimate the odds ratios (ORs) and 95% CIs of achieving different blood pressure categories at different thresholds . Four blood pressure categories were considered: normotension, elevated blood pressure, stage 1 hypertension, and stage 2 hypertension. Univariate and multivariable logistic regression analyses were used to estimate the ORs and 95% CIs of achieving blood pressure levels below stage 2 hypertension. The multivariable logistic regression and multivariable ordinal logistic regression models were both mutually adjusted for sex, age category, baseline BMI category, baseline Nutriscore, change in Nutriscore, change in weight, baseline SBP, baseline DBP, diabetes, and high cholesterol.t tests to evaluate whether the changes in SBP and DBP were statistically significant. In addition, we calculated the mean percentage change for SBP and DBP. In a sensitivity analysis, we used a threshold of stage 1 hypertension or higher (SBP ≥130 mmHg or DBP ≥80 mmHg) to calculate mean changes in HbA1c.Among participants who had stage 2 hypertension, we calculated the mean changes in SBP and DBP overall, and by time of follow-up at different thresholds . We used paired We also calculated the percentage of participants with stage 2 hypertension at baseline who achieved stage 1 hypertension or lower by the end of follow-up, and stratified by follow-up length.To further explore the impact on SBP and DBP, we examined changes in weight, diet quality, SBP, and DBP, stratified by whether participants with stage 2 hypertension at baseline achieved stage 1 hypertension or lower (SBP <130 mmHg and DBP <80 mmHg) by the end of follow-up.P values less than .05 to be significant for all tests. R Studio version 1.4.1106 and R version 4.0.5 (R Foundation) were used for all analyses.We considered The study was declared exempt from institutional review board oversight by the Pearl Institutional Review Board given the retrospective design of the study and the less than minimal risk to participants.Baseline demographics and biometrics of the total study sample stratified by a threshold of stage 2 hypertension status are shown in P=.28).There were 11,934 participants included in the total study sample; 69.93%  of the participants were female, 19.44%  were 60 years or older, 68.46%  were either overweight or obese, 17.80%  reported having diabetes, and 37.91%  reported having high cholesterol. The mean weight was 83.9 (SD 22.1) kg, the mean baseline Nutriscore was 33.8 (SD 8.5) points, and the mean change in the Nutriscore was 1.7 (SD 7.1) points. The mean follow-up length was 8.8 (SD 9.5) months and ranged from 1 to 65 months. Compared with participants who did not have stage 2 hypertension, participants who did have stage 2 hypertension were more likely to be male, to have a higher weight and BMI, to have a lower baseline Nutriscore, to have a longer length of follow-up, and to self-report having diabetes or high cholesterol. Participants with stage 2 hypertension at baseline were also more likely to have a higher increase in Nutriscore compared with participants without stage 2 hypertension at baseline, although the difference was not statistically significant (P=.02). Participants with a higher baseline Nutriscore were less likely to end in the elevated blood pressure or higher categories versus the normotensive blood pressure category on average . Participants whose Nutriscore increased at the end of follow-up were less likely to end in the elevated blood pressure or higher categories versus the normotensive category . Participants who gained more weight at the end of follow-up were more likely to end in the elevated blood pressure or higher categories versus the normotensive category on average .To better understand what blood pressure category participants attained at the end of follow-up, we used ordinal logistic regression to examine the association of covariates with the end blood pressure categories among participants who had stage 2 hypertension at baseline . ThreshoP=.001); for every 2-point increase in Nutriscore, a participant was 7% less likely to end in the elevated blood pressure or higher categories versus the normotensive category on average. Change in weight was positively associated with ending in the elevated blood pressure or higher categories . For every 1-kg increase in weight, a participant was 2% more likely to end with elevated blood pressure or higher versus normotension, on average.After adjusting for all other covariates in the multivariable ordinal logistic regression model, change in Nutriscore was inversely associated with ending with elevated blood pressure, stage 1 hypertension, or stage 2 hypertension . Participants classified in the age group 60 years and older were 68% more likely to achieve an end blood pressure category below stage 2 hypertension than participants classified in the less than 40-year-old group . Participants with a higher baseline Nutriscore were more likely to achieve an end blood pressure category below stage 2 hypertension . Participants with an increase in Nutriscore were more likely to achieve an end blood pressure category below stage 2 hypertension . Participants with a decrease in weight were more likely to achieve an end blood pressure category below stage 2 hypertension . Participants with a longer length of follow-up were more likely to achieve an end blood pressure category below stage 2 hypertension .We further examined the association between baseline characteristics and odds of achieving a blood pressure category below stage 2 hypertension in the univariate and multivariable logistic regression models . In the P=.01). In addition, adjusting for all other covariates, for every 2-point increase in change in Nutriscore, a participant would be 7% more likely to achieve an end blood pressure category below stage 2 hypertension . Adjusting for all other covariates, for every 1-kg increase in change in weight, a participant would be 2% less likely to achieve an end blood pressure category below stage 2 hypertension .After adjusting for all other covariates in the multivariable logistic regression model, we found that for every 2-point increase in baseline Nutriscore, a user would be 5% more likely to achieve an end blood pressure category below stage 2 hypertension , –2.4 (SD 10.1), –3.0 (SD 10.3), and –2.7 (SD 9.9) mmHg, respectively. Mean percentage changes in SBP were –1.3% (SD 6.9%), –1.6% (SD 7.2%), –2.0% (SD 7.4%), and –1.8% (SD 7.1%) for overall, ≥6, ≥12, and ≥24 months, respectively. The mean changes in DBP for overall and subsetting to length of follow-up ≥6, ≥12, and ≥24 months were –1.8 (SD 6.9), –2.1 (SD 6.9), –2.5 (SD 7.3), and –2.4 (SD 7.1) mmHg, respectively. The mean percentage changes in DBP were –1.9% (SD 7.4%), –2.3% (SD 7.5%), –2.7% (SD 8.1%), and –2.6% (SD 7.6%) for overall, ≥6, ≥12, and ≥24 months, respectively. Using paired We evaluated the percentage of participants who had stage 2 hypertension at baseline who achieved blood pressure levels below stage 2 hypertension, systolic reading <140 mmHg and diastolic reading <90 mmHg, at the end of follow-up . Across We examined the change in weight and Nutriscore for participants who lowered their blood pressure levels to below stage 2 hypertension versus those who remained in the stage 2 hypertension category . ParticiIn this study, we found that 10.63%  of Foodsmart participants had stage 2 hypertension at baseline. Foodsmart participants with stage 2 hypertension at baseline were more likely to be male, older, have a higher weight and BMI, have additional comorbidities , have a lower Nutriscore, and have a longer follow-up. For participants with stage 2 hypertension, blood pressure reduced by 5.7 mmHg/4.0 mmHg on average over a follow-up of 9.8 (SD 10.9) months. Among participants with stage 2 hypertension at baseline, 33.02% (419/1269) lowered their blood pressure to stage 1 hypertension or below. Furthermore, there were greater reductions in weight changes and increases in Nutriscores among those with stage 2 hypertension at baseline who achieved blood pressure levels below stage 2 hypertension. Our findings suggest that participant use of Foodsmart may be associated with reductions in blood pressure for patients with stage 2 hypertension.2 (categorized as obese) has been associated with a 3.5 times higher likelihood of developing hypertension. In addition, previous research has shown that diabetes and hypertension often occur together because they are mediated by similar physiologic conditions, such as impaired circadian blood pressure rhythm, renin-angiotensin-aldosterone blood pressure system dysregulation, microvascular and macrovascular damage, and more [Previous research confirms several of our findings. Through Korea’s National Health and Nutrition Examination Survey, Noh et al  confirmeand more ,18. Finaand more . Dyslipiand more  found a Individuals with hypertension are estimated to incur US $1920 higher incremental health care expenditures and nearly triple the medication expenditures compared with individuals without hypertension . Drugs sThere are some important limitations to note for this study. The first is that blood pressure values were self-reported and not clinically validated. Given that only blood pressure values were reported, we do not have information on which blood pressure devices were used or if standard protocol, such as the average of 3 consecutive measurements, was used. We assumed participants inputted their last recorded blood pressure values from a clinical setting. Nevertheless, we have reason to believe these values should still be approximately accurate, because blood pressure is not a required input for the app, and therefore those who did input blood pressure were most likely motivated by personal tracking. In addition, because values were self-reported, follow-up time was based on when the biometrics were entered as opposed to when blood pressure was measured. Therefore, the first measurements of SBP and DBP recorded may not necessarily align with the beginning of Foodsmart enrollment. Another possible issue is selection bias for individuals with hypertension who use Foodsmart. Those with hypertension who use the app may be more likely to make lifestyle changes because they are using the app for the purposes of improving their nutrition. These users may also be working to make lifestyle changes outside of the app that affect their blood pressure. Therefore, we cannot state that Foodsmart caused these changes in blood pressure. To make statements about causation, a randomized controlled trial must be conducted. Next, we were not able to collect data on other factors that might affect hypertension status. For instance, participants’ personal or family medical histories may have an influence on hypertension status. We lack information on whether participants were taking blood pressure medications before or during usage of the Foodsmart platform or if participants changed blood pressure medication during enrollment. Finally, we did not have data on socioeconomic factors, such as education, which may confound the associations. Further research is necessary to understand these additional variables. We also did not examine the frequency of Foodsmart app use, which may affect the associations found in our analyses.Our analysis also has many strengths. This is the first study to examine the real-life impact of behavioral change as a result of online food ordering, dietary education, and meal planning through a digital intervention and its impact on hypertension. Through analyzing data from Foodsmart’s large user base, we were able to gather information about real-world associations between changes in diet and blood pressure levels. Furthermore, Foodsmart participants had a wide range of enrollment lengths, which allowed us to evaluate changes in blood pressure over different lengths of time, including follow-up time of more than 2 years.In summary, this study assessed changes in self-reported SBP and DBP for participants using a digital nutrition platform that offers personalized meal planning, food ordering, grocery discounts, and price comparisons. Further research through a randomized clinical trial is warranted to evaluate the causal effect between the use of the Foodsmart platform and changes in blood pressure among participants.