Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: a systematic review and meta-analysis.

The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence interval, -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% confidence interval, 0.6-15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% confidence interval, 0.1-0.8; P=0.02), but not midodrine (means difference=0.5; 95% confidence interval, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.

Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of thereviewto evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the preventionof primary hypertension. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and theUS National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence. The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eightstudies; I2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; sevenstudies ; I2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies = 8; I2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events. An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of thereviewto evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the preventionof primary hypertension. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and theUS National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence. The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eightstudies; I2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; sevenstudies ; I2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies; I2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events. An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

BackgroundThis systematic review and meta-analysis aimed to determine the effectiveness of olive leaf extract on cardiometabolic profiles among prehypertensive and hypertensive groups. MethodologyThe Cochrane central register of controlled trials, Medline (1966 to April week 1, 2020), Embase (1966 to April week 1, 2020) and trial registries for relevant randomized clinical trials were used. Published and unpublished randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the continuous outcomes and mean differences (MDs); both with 95% confidence intervals (CIs). The primary outcomes were changes in systolic and diastolic BP. The secondary outcomes were changes in lipid profile, glucose metabolism, inflammatory markers for CVD, kidney and liver functions safety parameters. We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence.ResultsFive trials were included involving 325 patients aged 18–80 years. Two trials involved high-income countries and three trials involved moderate-income countries. The analysis performed was based on three comparisons. No significant changes were found between systolic or diastolic blood pressure (BP) for the first comparison, 1,000 mg per day for a combined formulation of olive leaf extract versus a placebo. The second comparison, 500 mg per day of olive leaf extract versus placebo or no treatment, showed a significant reduction in systolic BP over a period of at least 8 weeks of follow up (MD −5.78 mmHg, 95% CI [−10.27 to −1.30]) and no significant changes on diastolic BP. The third comparison, 1,000 mg per day of olive leaf extract versus placebo shows no significant difference but an almost similar reduction in systolic BP (−11.5 mmHg in olive leaf extract and −13.7 mmHg in placebo, MD 2.2 mmHg, 95% CI [−0.43–4.83]) and diastolic BP (−4.8 mmHg in olive leaf extract and −6.4 mmHg in placebo, MD 1.60 mmHg, 95% CI [−0.13–3.33]). For secondary outcomes, 1,000 mg per day of olive leaf extract versus captopril showed a reduction in LDL (MD −6.00 mg/dl, 95% CI [−11.5 to −0.50]). The 500 mg per day olive leaf extract versus placebo showed a reduction in inflammatory markers for CVD IL-6 (MD −6.83 ng/L, 95% CI [−13.15 to −0.51]), IL-8 (MD −8.24 ng/L, 95% CI [−16.00 to −0.48) and TNF-alpha (MD −7.40 ng/L, 95% CI [−13.23 to −1.57]).ConclusionsThe results from this review suggest the reduction of systolic BP, LDL and inflammatory biomarkers, but it may not provide a robust conclusion regarding the effects of olive leaf extract on cardiometabolic profile due to the limited number of participants in the included trials.Review registrationsPROSPERO CDR 42020181212.

A novel coronavirus disease broke out in 2019 (COVID-19). This disease was found to be a result of infection from the 2019 novel coronavirus (2019-nCoV).1 The severity of COVID-19 disease ranges from asymptomatic to critically severe; clinical research reported that 10–15% of the patients were in the severe category and required a great deal of medical treatment and nursing care.2 Indicators are needed to evaluate and predict the severity of the disease. We conducted the present meta-analysis to clarify whether platelet count might be a potential indicator to evaluate and predict the severity of COVID-19 in patients. Relevant studies published in English up to 30 April 2020 were searched through PubMed Scopus, EMBASE, Web of Science and Cochrane Library. Keywords included "COVID-19", "platelet count", "severe" and "thrombocytopenia". To be included in the analysis, the studies had to report the mean and (±standard deviation, SD) of the platelet count in both severe and non-severe COVID-19 patients, or report the median and interquartile range (IQR) or median and range of platelet count, from which we could extract information about the mean (±SD).3, 4 The studies that reported the proportions of patients with thrombocytopenia in both severe and non-severe COVID-19 were also included. Studies were excluded when the participants might have a large overlap with other included studies. Study quality was evaluated by a checklist from the Agency for Healthcare Research and Quality. The pooled standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were worked out by STATA 12.0 software (StataCorp LCC, College Station Texas, USA), and shown in the forms of forest plots figures. The detailed statement of materials and methods is shown in Data S1. After a comprehensive search and review (Figure S1), 31 studies with 7613 participants were included. Twenty-five of the included studies reported the platelet count of both severe and non-severe COVID-19 patients and 15 of the included studies reported the proportion of thrombocytopenia in both severe and non-severe COVID-19 patients. Detailed information and the reference list of included studies are shown in Tables SI and SII. For the 25 studies that reported the platelet count of both severe and non-severe COVID-19 patients, the pooled SMD revealed a lower platelet count in severe patients than non-severe patients (SMD = −0·36, 95% CI −0·48 to − 0·23, I2 = 56·9%; shown in Fig 1A). The results of a sensitivity analysis and test of publication bias are shown in Figures S2 and S3. Six of the 25 studies defined death as the severe state. The pooled SMD revealed a much lower platelet count in non-survivor COVID-19 patients than survivor patients (SMD = −0·60, 95% CI −0·72 to − 0·47, I2 < 0·1%; shown in Fig 1B). Fifteen of the 31 included studies reported the proportion of thrombocytopenia in both severe and non-severe COVID-19 patients. The pooled OR of thrombocytopenia for severe COVID-19 patients indicated a significant association between thrombocytopenia and severe COVID-19 (OR = 3·46, 95% CI 1·72–6·94, I2 = 91·8%; shown in Fig 2A). The results of a sensitivity analysis and test of publication bias are shown in Figures S4 and S5. Three of the 15 studies defined death as the severe state. The pooled OR suggested a stronger association between thrombocytopenia and death caused by COVID-19 (OR = 11·75, 95% CI 3·51–39·31, I2 = 88·9%; shown in Fig 2B). Abnormal platelet count, especially thrombocytopenia, is quite common in patients in the intensive care unit (ICU).5 The decreasing platelet count usually indicates the dysfunction of organs or systems and leads to a disorder of homeostasis. Studies found that thrombocytopenia in the ICU tended to increase the risk of death.6 It has also been reported that 2019-nCoV infection might affect the blood coagulation mechanism resulting in a disorder of blood coagulation.7 The mechanism by which 2019-nCoV affects blood coagulation might be similar to that of severe acute respiratory syndrome (SARS) which broke out in 2002 to 2003. The possible mechanism of thrombocytopenia in the SARS disease might be due to damage to the lung. The damage to the lung caused by the SARS corona virus, or mechanical ventilation, might lead platelet activation and aggregation, resulting in platelet consumption and thrombocytopenia.8 The lung has also been found to be a site of platelet biogenesis.9 Fibrosis and other lung damage might affect the formation and releasing of platelets. Collins10 reported that infection of the human coronavirus strain 229E could cause apoptosis in human monocytes/macrophages, which suggested that 2019-nCoV might damage the hematopoietic cells or platelet directly. However, the exact mechanism of how 2019-nCoV affects platelet count still needs to be explored. In conclusion, when compared to the non-severe COVID-19 patients, the patients with severe COVID-19 had a lower platelet count. The non-survivors had a much lower platelet count than the survivors. Thrombocytopenia might be a risk factor for COVID-19 progressing into a more severe state. More studies about platelet count in COVID-19 are needed. We wish to express our appreciation to all the authors whose publications could be included in our meta-analysis. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no conflict of interest. Shi-Qin Jiang, Qiu-Fen Huang and Wei-Ming Xie are joint first authors and contributed equally to the present meta-analysis; Shi-Qin Jiang, Wei-Ming Xie and Xiao-Qing Quan conceived the analysis; data was extracted by Qiu-Fen Huang and Wei-Ming Xie independently; Shi-Qin Jiang, Qiu-Fen Huang and Wei-Ming Xie analysed and interpreted the data; Shi-Qin Jiang and Chao Lv drafted the initial manuscript; the manuscript was critically revised by Xiao-Qing Quan for important intellectual content. All authors read and approved the final manuscript. All authors accept full responsibility for the content of the present article. Fig S1. Flow diagram of literature search and study selection. Fig S2. Result of sensitivity analysis for standardized mean difference (SMD) of platelet count between severe and non-severe COVID-19 patients. The middle vertical line indicates the pooled SMD of 25 studies, and the two side vertical lines represent the 95% confidence interval (CI) values. Every hollow round indicates the pooled SMD when the left study was omitted in a meta-analysis with a random-effect model. Fig S3. Begg's funnel plot of the 25 studies reported the platelet count of both severe and non-severe COVID-19 patients. The horizontal line indicates the pooled standardized mean difference (SMD). The asymmetry of two oblique lines was tested by Egger's linear regression test (P = 0·328). Fig S4. Result of sensitivity analysis on odds ratios (OR) of thrombocytopenia for severe COVID-19 patients. The middle vertical line indicates the pooled OR of 15 studies, and the two side vertical lines represent the 95% confidence interval (CI) values. Every hollow round indicates the pooled OR when the left study was omitted in a meta-analysis with a random-effect model. Fig S5. Begg's funnel plot of the 15 studies reported the proportion of thrombocytopenia in both severe and non-severe COVID-19 patients. The horizontal line indicates the pooled odds ratio (OR). The asymmetry of two oblique lines was tested by Egger's linear regression test (P = 0·735). Table SI. Characteristics of studies reported the platelet count in both severe and non-severe COVID-19 patients. Table SII. Characteristics of studies reported the proportion of thrombocytopenia in both severe and non-severe COVID-19 patients. Data S1. Materials and methods. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Hypertension among people with chronic kidney disease (CKD) is an established risk factor for acceleration of atherosclerotic cardiovascular disease and progression of kidney injury to end-stage renal disease (ESRD).1, 2 Randomized trials have demonstrated that blood pressure (BP)-lowering is translated into a profound benefit on cardiovascular and kidney outcomes.1 However, the optimal levels at which BP should be targeted remains an area surrounded by substantial controversy that is reflected by the discrepancy in BP target recommendations for patients with CKD across guidelines released during 2012-2018 (Table 1). The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guideline recommended a lower BP target of <130/80 mmHg only for CKD patients with persistent albuminuria [defined as albuminuria ≥30 mg/24-h or urinary-albumin-to-creatinine-ratio (UACR) ≥30 mg/g in a random urine specimen].2 In contrast, the 2014 guideline released by the eighth Joint National Committee (JNC8) did not differentiate the BP targets by the level of albuminuria. There was a uniform recommendation to lower BP to levels <140/90 mmHg regardless of the level of kidney function or UACR.5 The controversy was further magnified in more recent guidelines released after the publication of the Systolic Blood Pressure Intervention Trial (SPRINT).6 This landmark trial was prematurely terminated because of an impressive cardiovascular benefit with a lower (<120 mmHg) vs a standard (<140 mmHg) systolic BP (SBP) target in non-diabetic patients with clinic BP ≥ 130/80 mmHg and a high cardiovascular risk profile. Based on the results of SPRINT, the 2017 American Heart Association/American College of Cardiology (AHA/ACC) guideline reappraised the definition of hypertension and recommended a lower BP target of <130/80 mmHg for all patients at high cardiovascular risk, including those with CKD.4 The European Society of Hypertension/European Society of Cardiology (ESH/ESC) did not follow the same approach. In their 2018 guideline, the recommendation for patients with CKD was to lower SBP within the range of 130-139 mmHg and to individualize the intensity of treatment based on its tolerability.3 In this article, we explore the above-described heterogeneity across recent guidelines, providing a critical evaluation of randomized trials that compared a lower vs a standard BP target among patients with CKD. We raise the issue of research-grade BP monitoring method that was implemented in SPRINT and we ask the question whether the impressive results of this trial can be translated into benefit for our patients when intensification of antihypertensive therapy is guided by routine clinic BP recordings. The effect of intensive BP-lowering on kidney outcomes was explored in three separate randomized trials that enrolled non-diabetic patients with CKD (Table 2). The Modification of Diet in Renal Disease (MDRD) followed a 2 × 2 factorial design and randomized 840 patients with GFR 13-55 mL/min/1.73 m2 to two different levels of dietary protein intake and to achieve a lower mean BP (MBP) of <92 mmHg (approximately <125/75 mmHg) vs a standard MBP of 102-107 mmHg (approximately 135/85-140/90 mmHg).7 Over a 2.2-year-long follow-up, the rate of GFR decline did not differ between the lower- and standard-MBP arms. Intensive BP-lowering did not improve the combined outcome of ESRD or death [relative risk (RR): 0.85; 95% confidence interval (CI): 0.60-1.22].7 In the African American Study of Kidney Disease and Hypertension (AASK), 1094 African Americans with hypertensive nephrosclerosis were randomized to a lower vs a standard MBP target (<92 mmHg vs 102-107 mmHg) and to initiate antihypertensive therapy with metoprolol (50-200 mg/d), ramipril (2.5-10 mg/d), or amlodipine (5-10 mg/d) in a 2 × 3 factorial design.8 Over a follow-up of 3-6.4 years, compared with the standard MBP target, intensive BP-lowering had no benefit on the combined outcome of ≥50% decline in GFR, ESRD, or death (risk reduction: 2%; 95% CI: −22% to 21%).8 In the Ramipril Efficacy in Nephropathy trial 2 (REIN-2), 338 patients with non-diabetic, proteinuric CKD already treated with ramipril (2.5-5 mg/d) were randomized to intensified BP-lowering (goal BP <130/80 mmHg) or to standard BP control (diastolic BP <90 mmHg).9 Add-on therapy with felodipine (5-10 mg/d) was administered to achieve the assigned BP targets. REIN-2 was prematurely terminated at a median follow-up of 19 months due to futility. The risk of ESRD was similar in the intensive- and standard-BP groups (HR: 1.00; 95% CI: 0.61-1.64).9 Thus, during their randomized phase, none of these three trials showed that intensive BP-lowering is an effective strategy to halt the progression of kidney injury to ESRD. Post hoc analyses of the MDRD and AASK trials, however, support the notion that the level of proteinuria may act as treatment effect modifier. When MDRD participants were stratified into subgroups by the level of proteinuria at baseline, intensive BP-lowering was associated with a slower rate of GFR decline during follow-up in those with baseline proteinuria of 1-3 g/d or >3g/d. In the proteinuria stratum of <1 g/d, the rate of GFR decline did not differ between the lower- and standard-MBP arms.7 After the completion of the trial phase of AASK, participants were inserted into a cohort phase during which their BP was targeted to levels <130/80 mmHg. Over the entire follow-up of 9.1 years (trial plus cohort phase), the composite outcome of doubling of serum creatinine, ESRD, or death did not differ between those initially randomized to the lower vs those initially randomized to the standard MBP target (HR: 0.91; 95% CI: 0.77-1.08).11 However, there was a significant interaction between the randomized arm and level of baseline proteinuria for the composite kidney outcome (P = .02 for the interaction). In those with proteinuria >0.22 g/d, initial randomization to the lower BP target was associated with 27% reduction in the composite kidney outcome (HR: 0.73; 95% CI: 0.58-0.93). This benefit was not evident in those with baseline proteinuria ≤0.22 g/d (HR: 1.18; 95% CI: 0.93-1.50).11 Another post hoc analysis incorporating data from 840 MDRD participants with an extended follow-up of 9.2 years (trial plus cohort phase) showed that compared with the standard BP target, those initially randomized to intensive BP-lowering had 32% reduced risk of developing ESRD (HR: 0.68; 95% CI: 0.57-0.82).12 Based on this evidence, the 2012 KDIGO guideline recommended a lower BP target of <130/80 mmHg for CKD patients with persistent albuminuria.2 It has to be noted, however, that the strength of this recommendation was labeled as level 2 and the quality of evidence supporting this guidance was graded as level C. This guidance was based mainly on low-quality evidence from the aforementioned post hoc analyses of the MDRD and AASK trials. The observational nature of this data cannot demonstrate direct cause-and-effect associations. This scientific basis was considered insufficient/weak to mandate a reappraisal of BP targets for CKD patients in JNC8.5 Thus, the discrepancy between these two guidelines is not so large. In our interpretation, a level 2C recommendation by the 2012 KDIGO guideline is a clear recognition of the gap in the existing evidence and a call for future research. The effect of intensive BP-lowering on cardiovascular morbidity and all-cause mortality was evaluated in a prespecified post hoc analysis of 2,646 SPRINT participants with eGFR of 20-59 mL/min/1.73 m2.10 The separation between the intensive- and standard-arm was an average difference of −12.3 mmHg in SBP levels. Intensively treated participants required on average ~1 additional antihypertensive medication to achieve the assigned SBP target. This post hoc analysis showed the absence of interaction between the randomized arm and the level of eGFR at baseline for the primary cardiovascular outcome of SPRINT (P ≥ .30 for the interaction). The occurrence of the primary cardiovascular outcome did not differ between the intensive- and standard-arm (HR: 0.81; 95% CI: 0.63-1.05),10 possibly because this post hoc analysis was underpowered to detect a significant between-arm difference in the subgroup of SPRINT participants with eGFR <60 mL/min/1.73 m2. However, intensive BP-lowering provoked a significant 28% reduction in the risk of all-cause death (HR: 0.72; 95% CI: 0.53-0.99).10 Intensive BP-lowering in this post hoc analysis of SPRINT had no benefit on the composite kidney outcome of ≥50% decline in eGFR or ESRD (HR: 0.90; 95% CI: 0.44-1.83).10 Notably, this composite kidney outcome occurred in only 15 participants in the intensive-arm and in 16 participants in the standard-arm. This low incidence rate is not surprising, since patients with proteinuria >1 g/d who would presumably carry a higher risk of kidney injury progression were excluded from SPRINT. Although this trial was not originally designed to assess the efficacy of intensive BP-lowering on kidney outcomes like MDRD and AASK, the results of SPRINT were interpreted as a proof of the cardioprotective benefit of this strategy and provided the scientific basis to recommend a lower BP target of <130/80 mmHg for patients with CKD in the 2017 AHA/ACC guideline.4 The same clinical-trial evidence was interpreted differentially by the 2018 ESH/ESC guideline3 and the question that arises is whether the more conservative approach of European hypertension specialists is reasonable and evidence-based. Of note, the 2018 ESH/ESC guideline3 provided a more conservative recommendation on BP targets particularly for patients with CKD and not for other patient populations. Whether this differentiation is attributable to issues related to the tolerability of intensive BP-lowering in the CKD setting (ie, higher prosperity of these patients to adverse events, higher risk of acute kidney injury episodes, etch) or to other reasons remains another area of uncertainty. The diagnostic accuracy, reproducibility, and predictive value of BP recordings taken at the environment of clinic should be interpreted within the context of the actual methodology implemented (such as, type of BP monitor, the seated rest period before BP measurement, the presence of observer, the number of BP recordings).13 In SPRINT, clinic BP was measured with a fully automated oscillometric device that obtained triplicate recordings after a 5-minute seated rest and often without the presence of observer.6 This research-grade BP monitoring technique differs substantially from routine clinic BP recordings. A meta-analysis of 31 diagnostic-test studies (incorporating data from 9279 participants) showed that fully automated clinic SBP was similar with the reference-standard ambulatory daytime SBP [mean difference (MD): 0.3 mmHg; 95% CI: −1.1 to 1.7 mmHg].14 In contrast, routine clinic SBP overestimated ambulatory daytime SBP by 14.5 mmHg (MD: 14.5 mmHg; 95% CI: 11.8-17.2 mmHg).14 The importance of standardization in BP measurement methodology was highlighted by another meta-analysis of 10 diagnostic-test studies showing that unattended recordings were similar with attended clinic BP recordings, when the same device and measurement methodology was implemented.15 These meta-analyses, however, quantified only the average differences between BP monitoring techniques and did not explore their actual levels of agreement. In a diagnostic-test study that included 275 patients with stage 3-4 CKD and clinic BP <140/90 mmHg, participants underwent clinic BP monitoring with the research-grade technique that was implemented in SPRINT. On the same day, participants had their clinic BP recorded without specification of a 5-minute seated rest.16 Research-grade clinic SBP was by 12.7 mmHg lower than routine clinic SBP (MD: −12.7 mmHg; 95% CI: −14.7 to −10.7 mmHg) and the 95% levels of agreement between these two techniques were ranging from −46.1 to 20.7 mmHg. Research-grade clinic SBP underestimated the reference-standard ambulatory daytime SBP by 7.9 mmHg (MD: −7.9 mmHg; 95% CI: −9.4 to −6.4 mmHg), whereas the 95% levels of agreement were once again wide and were ranging from −33.2 to 17.4 mmHg. Whereas fully automated clinic SBP and ambulatory daytime SBP were significantly associated with echocardiographically documented left ventricular hypertrophy, routine clinic SBP could not detect evidence of target-organ damage.16 Taken together, the above evidence from diagnostic-test studies suggests that the differentiation in recommended BP targets between the American and European guidelines may be simply the tip of the iceberg. Guideline groups have taken into consideration the above-described variability between research-grade and routine clinic BP recordings. Recognizing that the adoption of a research-grade BP monitoring technique like that of SPRINT in daily clinical practice would probably be problematic, the recommended BP targets were adjusted to a higher level from that of the achieved clinic SBP of 121.2 mmHg in the intensive-arm of SPRINT. In our interpretation, a lower or a higher algebraic adjustment for the average bias inserted by routine clinic BP recordings remains an oversimplification.17 An algebraic adjustment for the average differences provides little to no reflection of the actual variability between research-grade and routine clinic BP at the level of individual patients, given the wide 95% levels of agreement between these two techniques in diagnostic-test studies.16 Thus, implementation of intensive BP targets in daily clinical practice necessitates the optimization of our BP measurement methodology. In other words, if antihypertensive therapy continues to be guided by what is already done in routine clinical practice, then intensive BP-lowering may not be beneficial. Evidence to support that intensive BP-lowering to levels <130/80 mmHg is an effective strategy to delay the progression of kidney injury to ESKD is weak. All randomized trials that compared a lower vs a standard BP target in patients with CKD failed to show a benefit of intensive BP-lowering on kidney outcomes.7-9 The notion that intensive BP-lowering is beneficial for those with proteinuric CKD is based on low-quality evidence from post hoc analysis of the MDRD and AASK with an extended observational follow-up after the completion of the randomized phase of these two trials.11, 12 In accordance with the results of MDRD, AASK, and REIN-2, in a post hoc analysis of 2646 SPRINT participants with eGFR <60 mL/min/1.73 m2, intensive BP-lowering did not improve the composite kidney outcome.10 This post hoc analysis, however, provided some evidence to support a potential benefit of intensive BP-lowering on survival and cardiovascular outcomes.10 Even if we interpret this evidence as a proof of cardioprotection, we believe that this benefit may not be generalizable to the majority of our patients if antihypertensive therapy continues to be guided by BP recordings taken under routine clinical practice conditions. In our view, individualization of the intensity of therapy based on its tolerability and optimization of our BP measurement methodology represent important steps to improve BP control and clinical outcomes in this high-risk population. The wider adoption of home or ambulatory BP monitoring is another important step to improve the management of hypertension among patients with CKD. The authors have no conflicts of interest to disclose. Literature search: PIG, VV; Drafting the manuscript: PIG; Revisions on the initial draft: PEZ, VL; Approval of the final paper: VV, VL, PEZ.

A mismatch between biological and social time, often referred to as social jetlag (SJL), can lead to inadequate sleep and activities or taking meals at times that do not align with our biological rhythms, increasing the risk of metabolic abnormalities. Although the association between sleep and metabolic syndrome (MetS) is well established, the effects of SJL on MetS and the components of MetS in adults remain unclear. This study was designed to explore the relationship between SJL and MetS components in adults. A systematic review and meta-analysis was conducted on studies registered in PubMed, Cochrane, Web of Science, and Embase between the inception of each database until November 15, 2023. We focused on studies designed to evaluate the relationship between SJL and either MetS or its components. Only studies using cross-sectional, prospective, or retrospective designs were considered for inclusion. The relationship between SJL and MetS was depicted as an odds ratio with a corresponding 95% confidence interval (CI). We determined the mean differences and 95% CIs to estimate the associations between SJL and MetS components. The Joanna Briggs Institute Critical Appraisal Checklist was used to evaluate the methodological rigor of the selected studies. Data were analyzed using RevMan software Version 5.4. The systematic review included 16 studies, with five analyzed via a meta-analysis covering four outcomes, each based on two to three studies. When comparing SJL of less than 1 hour with SJL of 2 hours or more, the latter showed a higher likelihood of MetS (pooled odds ratio: 1.52). Although a significant decrease in systolic blood pressure (pooled mean differences = -3.52 mmHg, 95% CI [-6.41, -0.64]) and a significant increase in waist circumference (pooled mean differences = 2.17 cm, 95% CI [0.61, 3.73]) were observed, the correlation between SJL and diastolic blood pressure failed to reach statistical significance. The meta-analysis conducted in this study found an association between SJL and MetS. Healthcare practitioners should prioritize the management of sleep quality and duration, especially for individuals exhibiting substantial SJL. Improving sleep can aid in controlling blood pressure and managing weight and should form part of MetS management strategies.

Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure. As small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges, this review intends to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, EMBASE and ClinicalTrials.gov for randomised controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register. We also reviewed reference lists from retrieved studies and contacted authors of relevant papers. We applied no language restrictions. We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We included 16 trials with 3048 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was mean difference (MD) -1.43 mmHg (95% confidence interval (CI) -2.15 to -0.72) and -0.98 mmHg (95%CI -1.46 to -0.50) respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years (7 trials with 399 participants) was -2.11 mmHg (95%CI -3.58 to -0.64) / -2.61 mmHg (95% CI -3.74, -1.49). The effect on systolic and diastolic blood pressure for those 35 years or more (9 trials with 2649 participants) was -0.96 mmHg (95%CI -1.83 to -0.09) / -0.59 mmHg (95%CI -1.13 to -0.06). The effect on systolic and diastolic blood pressure for women (6 trials with 1823 participants) was -1.45 mmHg (95% CI -2.78 to -0.12) / -0.92 mmHg (95% CI -1.71 to -0.14). The effect on systolic and diastolic blood pressure for men (5 trials with 617 participants) was -2.07 (95%CI -3.56 to -0.59] / -1.91 (95%CI -2.80 to -1.02).The quality of evidence for each of these outcomes was high. The effect is consistent in both genders regardless of baseline calcium intake.The effect on systolic blood pressure was 0.08 mmHg (95% CI -2.16 to 2.32) with doses less than 1000 mg, -1.14 mmHg (95% CI -2.01 to -0.27) with 1000 - 1500 mg, and -2.79 mmHg (95% CI -4.71 to -0.86) with more than 1500 mg. The effect on diastolic blood pressure was -0.54 mmHg (95% CI -2.23 to 1.15), -0.71 mmHg (95% CI -1.37 to -0.06) and -1.43 mmHg (95% CI -2.22 to -0.64) respectively. The quality of evidence for each of these outcomes was high.None of the studies reported adverse events. An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. These results should be interpreted with caution, since the proposed biological mechanism explaining the relationship between calcium and blood pressure has not been fully confirmed. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease.There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

BACKGROUND Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD). AIM To assess the association of CDI with clinical outcomes of IBD. METHODS PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched from inception to March 2024. Eligible articles included observational studies that reported on outcomes such as mortality, colectomy, hospitalization, intensive care unit (ICU) admission, complication rates, and length of hospital stay in IBD patients with and without CDI. Data were extracted, and a random-effects model was used to calculate pooled odds ratios (ORs) and mean differences (MDs). RESULTS As shown in the data from 21 studies with 1249158 participants, CDI significantly increased the risk of mortality in IBD patients [pooled OR = 4.569, 95% confidence intervals (95%CI): 2.584 to 8.079]. Although the pooled OR for colectomy was 1.409 (95%CI: 0.922 to 2.155), it was not statistically significant. Similarly, CDI did not impact hospitalization (pooled OR = 1.056, 95%CI: 0.512 to 2.179) and ICU admission outcomes (pooled OR = 1.970, 95%CI: 0.420 to 9.246) of patients with IBD. The rate of complications was comparable in the two groups (pooled OR = 0.658, 95%CI: 0.378 to 1.147). However, CDI was associated with a significantly more extended hospital stay (pooled MD = 0.349 days, 95%CI: 0.002 to 0.696). CONCLUSION CDI is linked to increased mortality and prolonged hospitalization in IBD patients. These results emphasize the need for early detection and appropriate management. Implementing routine CDI screening during IBD flare-ups and stringent infection control measures could mitigate severe complications and reduce the healthcare burden.

Oral microflora associated with periodontal disease (PD) has been proposed to be a causal factor for cardiovascular disease (CVD).Data from NHANES I and its 21-year follow-up were used to test this hypothesis.Baseline periodontal status was categorized into (1)no PD, (2)gingivitis, (3)periodontitis, and (4) edentulousness.CVD events during follow-up were ascertained by hospital records for non-fatal events and death certificates for fatal events.Relative risk (RR) and 95% confidence interval (CI) were derived from Cox regression after adjusting for demographic variables and several well-established CVD risk factors.9,962 people were free from coronary heart disease (CHD), heart failure, and cancer at baseline.2,844 CVD, 1,468 CHD, and 803 stroke events occurred during the follow-up.Compared to no PD, RRs (CI) of CVD were 1.05 (0.93-1.18) for gingivitis, 1.17 (1.04-1.31)for periodontitis, and 1.22 (1.10-1.34)for edentulousness.RRs (CI) at similar PD levels for CHD were 1.03 (0.87-1.21), 1.14 (0.98-1.34), and 1.13 (0.98-1.32), and for stroke were 1.03 (0.81-1.31), 1.33 (1.07-1.66),and 1.30 (1.06-1.60),respectively.Analyses stratified by age group indicated that elevated risk for CVD associated with PD is manifested mainly in those aged 25-54 years at baseline.Among this age group, RRs (CI) of CVD were 1.13 (0.96-1.33) for gingivitis, 1.40 (1.16-1.68)for periodontitis, and 1.36 (1.11-1.68)for edentulousness in comparison to no PD; RRs (CI) of CHD were 1.13 (0.80-1.29), 1.33 (1.03-1.72),and 1.25 (0.93-1.67); and RRs (CI) of stroke were 0.96 (0.64-1.46), 1.57 (1.05-2.36),and 1.46 (0.92-2.33), respectively.This study suggests that periodontal disease is a significant risk factor for CVD, CHD, and stroke especially in adults aged 25-54. P2 Stress in the workplace and early atherosclerosis. The Los Angeles

sponsorship: The European Union (HEALTH-F7-2011-278249 EU-MASCARA, HEALTH-F7-305507 HOMAGE and the European Research Council Advanced Researcher Grant 294713 EPLORE) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and G.0880.13) currently support the Studies Coordinating Centre (Leuven, Belgium). (European Union|HEALTH-F7-2011-278249 EU-MASCARA, European Union|HEALTH-F7-305507 HOMAGE, European Union (European Research Council)|294713 EPLORE, Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium|G.0881.13, Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium|G.0880.13)

Health literacy (HL) is the ability to access, understand, and apply health information to make informed decisions. However, evidence regarding the comprehensive effects of HL interventions on multiple outcomes in older adults with hypertension remains unclear. This study aimed to evaluate the effectiveness of HL interventions for improving systolic blood pressure (SBP), diastolic blood pressure (DBP), medication adherence, and self-efficacy in older adults with hypertension. We searched PubMed, Web of Science, Scopus, Embase, the Cochrane Library, and CINAHL from inception to June 2025 for relevant randomized controlled trials (RCTs). Study quality was assessed using the Cochrane RoB 2.0 tool. Pooled mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using random-effects models. Subgroup and sensitivity analyses were conducted. Forty-two RCTs (9,332 participants) were included; 25 studies (59.5%) had a low risk of bias. Meta-analysis revealed that HL interventions significantly reduced SBP (MD: -6.90 mmHg; 95% CI: -8.51 to -5.29; p < 0.01) and DBP (MD: -3.03 mmHg; 95% CI: -4.12 to -1.94; p < 0.01), and improved medication adherence (SMD: 0.69; 95% CI: 0.26 to 1.12; p < 0.01) and self-efficacy (SMD: 0.35; 95% CI: 0.10 to 0.60; p < 0.01). Greater benefits were observed in trials conducted in Eurasian regions and those emphasizing active participant engagement. HL interventions are effective in improving SBP and DBP control, medication adherence, and self‑efficacy among older adults with hypertension. The findings support the integration of structured, participatory HL strategies into routine geriatric hypertension management.

This study evaluated the effectiveness of morning versus bedtime antihypertensive medication administration in reducing ambulatory blood pressure (BP) in older adults aged ≥ 65, and to assess whether administration timing influences conversion from a non-dipper to a dipper BP profile. Eight randomized controlled trials were identified through systematically screening of the PubMed and Web of Science databases. Risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted with Review Manager version 5.4 to compare the efficacy of morning versus bedtime administration on ambulatory BP indices. Bedtime administration resulted in significantly greater reductions in nocturnal systolic BP (mean difference [MD] - 4.52mmHg, [lower and upper 95% confidence intervals [CI] - 7.15; - 1.90]; p = 0.0007) and diastolic BP (MD - 2.00mmHg, [95%CI - 2.90; - 1.10]; p < 0.0001). No significant differences were observed in diurnal systolic BP (MD 1.28mmHg, [95%CI - 0.17; 2.72]; p = 0.08), diastolic BP (MD 0.34mmHg, [95%CI - 0.49; 1.16]; p = 0.42), 24/48-h systolic BP (MD - 0.02mmHg, [95%CI - 1.37; 1.33]; p = 0.98), or 24/48-h diastolic BP (MD - 0.50mmHg, [95%CI - 1.45; 0.45]; p = 0.30). Sensitivity analysis excluding the controversial data from Hermida confirmed significantly greater reductions in nocturnal systolic and diastolic BP with bedtime administration. Two of three studies reported that bedtime administration was associated with a lower proportion of non-dippers than morning treatment. Bedtime antihypertensive administration improves control of nocturnal BP in older adults aged ≥ 65 and may facilitate restoration to a dipper BP profile. No significant differences were observed in diurnal or 24/48-h mean BP reductions compared with morning administration.

Hypertension is one of the most prevalent chronic conditions among older adults and a major contributor to cardiovascular morbidity and mortality. In Thailand, the aging population is rapidly increasing, and the burden of uncontrolled hypertension among older adults presents a significant public health challenge. Effective and sustainable strategies for hypertension management are therefore essential. Self-management interventions, grounded in behavioral and theoretical frameworks, have been widely promoted as a patient-centered approach to chronic disease control.This systematic review and meta-analysis aimed to assess the effectiveness of self-management theory based interventions in reducing blood pressure among older adults with hypertension in Thailand. A comprehensive search of both international and Thai databases—including PubMed,Embase, Scopus, and the Thai Journal Citation Index (TCI) was conducted to identify relevant studies published between January 2018 and December 2023. The review specifically included studies employing randomized controlled trial (RCT) or quasi-experimental designs involving self-management interventions targeting older adults aged 60 years and above diagnosed with hypertension. The selection process followed PRISMA guidelines. After rigorous screening and quality appraisal using the JBI Critical Appraisal Checklist for Quasi-Experimental Studies, only quasi-experimental studies were included as randomized controlled trials were absent from our search results. The results showed that five studies met the inclusion criteria. All included studies were conducted in Thailand, targeted older adults and implemented interventions grounded in self-management theoretical frameworks. These interventions commonly incorporated components such as health education, self-monitoring, behavior modification, goal setting, and reinforcement strategies, with the overarching aim of improving hypertension control and enhancing patient engagement. The five included studies encompassed a total of 379 older adults, with 188 participants assigned to various self-management intervention groups and 189 to control groups receiving usual care. Meta-analyses were conducted separately for systolic blood pressure and diastolic blood pressure outcomes using a random-effects model. The results demonstrated statistically significant reductions in both systolic blood pressure and diastolic blood pressure in the intervention groups compared to the control groups.For diastolic blood pressure, the pooled mean difference was -9.34 mmHg (95% confidence interval [CI]: -10.95 to -7.72), indicating a substantial improvement in blood pressure control associated with the interventions. The effect was statistically significant (z = -11.32, p &lt; 0.001).Similarly, for systolic blood pressure, the meta-analysis showed a mean difference of -16.79 mmHg (95% CI: -25.21 to -8.38), also favoring the intervention groups. The effect was statistically significant (z = -3.91, p &lt; 0.001).Overall, the findings from this review highlight the effectiveness of self-management theory based interventions in significantly lowering both systolic and diastolic blood pressure among older adults in Thailand. These interventions not only contribute to improved clinical outcomes but also promote patient autonomy and long-term adherence to treatment regimens—key components in managing a chronic condition such as hypertension. Given the growing emphasis on person-centered care in aging populations, these results support the integration of self-management programs into routine hypertension care, particularly in community and primary care settings. Despite these positive outcomes, some limitations should be acknowledged. Notably,the number of eligible studies was relatively small, which may limit the generalizability of the findings. Keywords: Hypertension, Meta-analysis, Older adults, Systematic review, Thailand

Hypertension (HTN) management continues to be a concern due to challenges with behavioral risk factors. Patient education to modify unhealthy behaviors appears to be effective in managing HTN. Therefore, this meta-analysis aimed to determine whether individualized face-to-face education and counseling have a beneficial effect on systolic and diastolic blood pressure (SBP and DBP) in hypertensive patients. Studies were extracted from PubMed, Scopus, Cochrane Library, and Web of Science databases. Nine studies, comprising 2627 participants, were included. Random effects models were used to pool estimates of mean differences (MDs) with 95% confidence intervals (CIs) in SBP and DBP between the intervention and usual care groups. SBP and DBP were significantly reduced at the 6-month (MD = -4.38 mmHg, 95% CI: -6.95 to -1.81; MD = -2.09 mmHg, 95% CI: -3.69 to -0.50, respectively) and 12-month time points (MD = -2.48 mmHg, 95% CI: -3.96 to -1.01; MD = -1.71 mmHg, 95% CI: -2.88 to -0.55, respectively) with intervention. At the 24-month time point, there was a significant change in SBP (MD = -2.13 mmHg, 95% CI: -3.94 to -0.32) with intervention compared with the usual care group. This study showed that individualized face-to-face education and counseling add significant benefits to usual care for lowering blood pressure in hypertensive patients. Graphical Abstract.