Night-time blood pressure dipping, but not 24-h blood pressure level, is linked to increased 24-h ocular volume slope

ABSTRACT Purpose: This study investigated the relationship between blood pressure and intraocular pressure in treatmentnaive, non-glaucoma patients with different blood pressure statuses, focusing on the 24-h ocular volume and nocturnal blood pressure decline. Methods: Treatment-naive, non-glaucoma patients undergoing hypertension evaluation were enrolled as study participants. Simultaneous 24-h ambulatory blood pressure measurement and 24-h ocular volume recording with a contact lens sensor. We also compared ocular volume curve parameters between normotensive and hypertensive patients, as well as between those with and without nocturnal blood pressure decline. Results: A total of 21 patients, including 7 normotensive and 14 treatment-naive hypertensive individuals, were included in the study. of them, 11 were dippers and 10 were non-dippers. No significant difference in the 24-h ocular volume slope was observed between the hypertensive and normotensive patients (p=0.284). However, dippers had a significantly higher 24-h ocular volume slope (p=0.004) and nocturnal contact lens sensor output (p=0.041) than non-dippers. Conclusion: Nocturnal blood pressure decline, rather than the blood pressure level, is associated with the increased 24-h ocular volume slope and nocturnal ocular volume. Further studies are required to determine whether the acceleration of glaucoma progression in dippers is primarily due to low blood pressure, high intraocular pressure, or a combination of both.

Efficacy and Safety of Sacubitril/Allisartan for the Treatment of Primary Hypertension.

Background: The prevalence of hypertension still increases with the very rapidly increasing longevity in some countries, such as China. The control rate remains low. Objectives: This randomized, double-blind, phase 3 study assessed the efficacy and safety of sacubitril/allisartan, compared with olmesartan in Chinese patients with mild-to-moderate hypertension. Methods: Eligible patients aged 18 to 75 years (n = 1,197) with mild-to-moderate hypertension were randomized to receive sacubitril/allisartan 240 mg (n = 399), sacubitril/allisartan 480 mg (n = 399), or olmesartan 20 mg (n = 399) once daily for 12 weeks. Patients who completed the 12-week treatment then received another 12-week extended treatment (n = 1,084) and 28-week prolonged treatment (n = 189). The primary end point was a reduction in clinic mean sitting systolic blood pressure (msSBP) from baseline at 12 weeks. Results: Sacubitril/allisartan 240 mg/d provided a greater reduction in msSBP than olmesartan at 12 weeks (between-group difference: -1.9 mm Hg [95% CI: -4.2 to 0.4 mm Hg]; P = 0.0007, for noninferiority). Sacubitril/allisartan 480 mg/d provided a significantly greater reduction in msSBP than olmesartan at 12 weeks (between-treatment difference: -5.0 mm Hg [95% CI: -7.3 to -2.8 mm Hg]; P < 0.001, for superiority). Greater reductions in 24-hour, and daytime and nighttime systolic and diastolic blood pressure were also observed with both doses of sacubitril/allisartan compared with olmesartan (P ≤ 0.001 for 480 mg/d). The blood pressure reductions tended to be dose-dependent for sacubitril/allisartan. Sacubitril/allisartan was well tolerated, and no cases of angioedema or death were reported. Conclusions: Sacubitril/allisartan is effective for the treatment of hypertension and well tolerated in Chinese patients.

Single-Pill Combination Therapy of Amlodipine, Telmisartan, and Chlorthalidone in the Management of Hypertension: A Systematic Review of Randomized Controlled Trials.

Hypertension is a major cause of cardiovascular disease and death worldwide. Low-dose combination therapy is a promising approach for managing hypertension due to its safety and efficacy. This systematic review evaluates the safety and efficacy of a single-pill, low-dose combination of amlodipine, telmisartan, and chlorthalidone for essential hypertension based on evidence from randomized controlled trials (RCTs). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched the Cochrane, Scopus, PubMed, and Web of Science databases until July 01, 2024, using the following search string: (telmisartan) AND (amlodipine) AND (chlorthalidone) AND (randomized OR randomly). The quality of the RCTs was assessed using the revised Cochrane risk of bias tool. The primary endpoint was the mean change in sitting systolic blood pressure (BP), with secondary endpoints including BP target achievement rates, BP response rates, and serious treatment-related adverse events. Overall, three RCTs met the inclusion criteria and exhibited a low risk of bias. The doses in the combination pill ranged from 2.5 to 5 mg of amlodipine, 20 to 80 mg of telmisartan, and 4.167 to 25 mg of chlorthalidone. Control groups varied, including usual care, amlodipine 10 mg, and dual therapy of telmisartan and amlodipine. Results showed significant reductions in mean sitting systolic and diastolic BP, improved BP control and response rates, and a generally safe profile with no significant differences in serious adverse events. Despite encouraging data, results should be interpreted with caution due to heterogeneity in doses and control groups. Further research should address the long-term effects and explore predictors of response to this therapy.

Impact of Angiotensin Receptor Blockers (ARB) versus Other Antihypertensive Medication on Blood Pressure in Patients on Dialysis: A Meta-Analysis.

Introduction: Hypertension is an important factor driving mortality among dialysis patients. Angiotensin-II receptor blocker (ARB) has been effective similarly to angiotensin-converting enzymes (ACEs) but with a low incidence of side effects. Methodology: The meta-analysis included all published studies that investigated the effect of ARB on the hypertension in adult dialysis patients (≥18 years). Data extraction was guided by a predetermined checklist. Data sources of the retrieved studies were PubMed, MEDLINE, ScienceDirect, SCOPUS, Cochrane, Web of knowledge, and Google Scholar were systematically searched until February 2023. Using the RevMan 5 software, the mean difference for systolic and diastolic BP (SBP and DBP) and the risk ratio (RR) of the adverse events (AEs) were pooled from the selected studies. The random-effects model was used to compare the difference in the pre-and post-dialysis of the SBP and DBP. Data analyses were performed from December 2022 to February 2023. The primary outcome was the reduction in SBP and DBP in dialysis hypertensive patients who were on anti-hypertensive agents, and the secondary outcome was assessment of AE associated with the drug after dialysis (PROSPERO Registration: CRD42022355369). Results: The initial search yielded 1,679 records, of which 84 studies underwent full-text evaluation, which identified 13 studies and 1,462 patients. The pooled standard MD for losartan with other anti-hypertensive agents, where the pre-dialysis SBP was 0.17 (95% confidence interval [CI]: -0.21-0.55) and the post-dialysis was 0.35 (95% CI: -0.17-1.02); yet, both are statistically non-significant, implies that there was no difference between Losartan and ARB drugs regarding the effect on the SBP. Diastolic BP for predialysis was -0.01 (95% CI: -0.65-0.63) and post-dialysis was 0.03 (95% CI: -0.24-0.30) and statistically non-significant. AEs by the ARB agents were lower compared to other anti-antihypertensive agents (relative risk [RR]: 1.01; 95% CI: 0.59-1.75) and statistically non-significant. Conclusion: This systematic review and meta-analysis of RCT demonstrated that ARB and other anti-hypertensive medications had similar impacts on the treatment of hypertension.

Digital ulcers in systemic sclerosis are strongly associated with digital arterial disease: a finger-by-finger analysis of Finger Brachial Pressure Index Measurements.

OBJECTIVES: The digital ulcers of systemic sclerosis are disabling and frequent· Their pathogenesis involves a capillary microangiopathy and a digital arterial disease that few studies were able to quantify up to now. A multicentre observational study about the predictive value of capillaroscopy in systemic sclerosis offered us the opportunity to evaluate further the complementary information provided by both capillary and arterial evaluations. METHODS: During the SCLEROCAP study, five out of the nine centers performed a systematic evaluation of the finger brachial pressure index (FBPI) in the last four fingers of both hands at baseline, using the same laser-doppler device. In the present work, FBPI measurements were compared between fingers with vs without digital ulcers or scars, before and after adjusting for the capillaroscopic pattern and systemic factors. RESULTS: FBPI measurements were performed in 2537 fingers from 326 patients. Active ulcers or scars were found in 10·8% of those fingers, more often on the right hand, and in the second and third fingers. FBPI was lower than 0·70 in 26% of all fingers and in 57·5% of those with ulcers. A strong association was found between a low FBPI and the presence of digital ulcers, even after adjusting for capillaroscopic pattern, ulcer location and the patient himself. CONCLUSION: These results confirm the importance of digital arterial disease in the pathogenesis of digital ulcers of systemic sclerosis, which is independent from the microangiopathy. FBPI measurements complement the information provided by capillaroscopy and might have an important predictive value for subsequent digital ulcers.

Understanding preeclampsia from cutting edge knowledge-protecting maternal and fetal health.

Preeclampsia (PE) is conventionally been defined clinically by new-onset or aggravating hypertension during pregnancy >20 weeks associated with proteinuria or other organ damages. PE is a major cause of maternal and fetal morbidity and mortality globally and expected to increase even more. Nevertheless, there are still much to be established regarding pathophysiology, prediction, prevention, and management of PE and thus, research concerning PE is being actively conducted. This mini-review discusses on latest knowledge on PE.

Practical use and target value of urine sodium-to-potassium ratio in assessment of hypertension risk for Japanese: Consensus Statement by the Japanese Society of Hypertension Working Group on Urine Sodium-to-Potassium Ratio.

Epidemiological studies have demonstrated that the urine sodium-to-potassium (Na/K) ratio is more positively associated with high blood pressure and cardiovascular disease risk than either urine sodium or potassium excretion alone. In this consensus statement, we recommend using the average Na/K ratio of casual urines randomly taken in various times on at least four days a week for a reliable individual estimate because of high day-to-day and intraday variability of casual urine Na/K ratio within individuals. Although a continuous positive association exists between the Na/K ratio and high blood pressure or cardiovascular disease risk, for clinical and public health decision making for Japanese, we recommend using an average urine Na/K ratio of 2 as an optimal target value because this aligns with recommendations for both sodium and potassium intake in the Dietary Reference Intakes for Japanese, 2020, considering a typical Japanese dietary pattern. We also suggest that an average urine Na/K ratio of 4 is a feasible target value to achieve a temporary goal of being below the mean values of the urine Na/K ratio across Japanese general populations. These recommendations apply mainly for apparently healthy individuals, but not for patients with specific conditions due to the lack of supporting data. Current evidence for the usefulness of measuring the urine Na/K ratio for the prevention or control of hypertension remains inconclusive and warrants further investigation.

Infertility treatment and offspring blood pressure-a systematic review and meta-analysis.

BACKGROUND: Studies have inconsistently observed that children conceived by IVF or ICSI have higher blood pressure compared to children not conceived by these ARTs. OBJECTIVE AND RATIONALE: The aim was to perform a systematic review and meta-analysis of blood pressure measures of offspring conceived by ART and those conceived naturally. Resolving the suspicion of ART as a risk factor of higher blood pressure, and therefore of heart disease, has public health and clinical implications. SEARCH METHODS: A biomedical librarian searched the Embase, PubMed, and Web of Science databases. Searches were limited to records published in English since 1978. Grey literature was searched. Inclusion criteria were humans born via infertility treatment (vs no treatment) who underwent a blood pressure assessment. Exclusion criteria were non-human participants, non-quantitative studies, absence of a control group, and specialty populations (e.g. cancer patients only). Two reviewers independently screened each record's title and abstract and full text using Covidence, extracted data using Excel, and assessed bias using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for cohort studies. OUTCOMES: Of 5082 records identified, 79 were included in the systematic review and 36 were included in the meta-analysis of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in ART and non-ART groups. Overall, 34 reports including 40 effect sizes from 25 unique cohorts, compared blood pressure between ART (N = 5229) and non-ART (N = 8509, reference) groups with no covariate adjustment. No standardized mean differences (SMD) in SBP (0.06 per SD of mmHg, 95% CI = -0.05, 0.18) or DBP (0.11, 95% CI = -0.04, 0.25) by treatment were found, but the heterogeneity was considerable (I2=76% for SBP and 87% for DBP). Adjusted analyses were presented in 12 reports, representing 28 effect sizes from 21 unique cohorts (N = 2242 treatment vs N = 37 590 non-treatment). Studies adjusted for varied covariates including maternal (e.g. age, education, body mass index, smoking, pregnancy complications), child (e.g. sex, age, physical activity, BMI, height), and birth characteristics (e.g. birth weight and gestational age). Adjusted results similarly showed no SMD for SBP (-0.03, 95% CI = -0.13, 0.08) or DBP (0.02, 95% CI = -0.12, 0.16), though heterogeneity remained high (I2 = 64% and 86%). Funnel plots indicated a slight publication bias, but the trim and fill approach suggested no missing studies. Removal of five studies which adjusted for birth outcomes (potentially over-adjusting for mediators) made no material difference. Type of treatment (e.g. IVF vs ICSI), period effects by birth year (≤2000 vs >2000), offspring age group (<8, 8-14, 15+), or study location (e.g. Europe) did not modify the results. WIDER IMPLICATIONS: In conclusion, conception by ART was not associated with offspring blood pressure in a meta-analysis, although considerable heterogeneity was observed. Given the increasing number of children born using ART, perpetuating a difference in blood pressure would mean unnecessary risk screening for many children/adults on a population level. At a clinical level, couples considering these reproductive technologies have some reassurance that there is no evidence of strong vascular 'programming' due to the techniques used. REGISTRATION NUMBER: PROSPERO No. CRD42022374232.

Barriers and enablers to salt intake reduction in Australian adults with high blood pressure.

High dietary salt intake is a known risk factor for hypertension. However, Australians continue to consume excessive amounts of salt. The purpose of this study was to identify barriers, enablers and strategies to reduce salt in a sample of Australian adults with hypertension. This was a qualitative study. Participants were asked a set of open-ended questions during focus groups conducted between October 2020 and April 2021. Sessions were recorded and transcribed. Using an inductive approach, the transcript data from the focus groups were thematically analysed. This involved checking accuracy, becoming familiar with the data, coding responses based on questions, identifying themes through common patterns and validating themes by grouping similar questions that represented the data and study aim effectively. Thirty-one adults (55 % females) with high blood pressure participated in the focus group discussions. Participants demonstrated good knowledge of high blood pressure risk factors but lacked an understanding of recommended salt intake levels and sources of hidden salt. Challenges in reducing salt intake included the limited availability of low-salt commercial foods. Participants suggested improved food labelling and the use of technology-based interventions to promote healthier choices. Findings highlight the need for behavioural interventions, policy reforms and collaborations between the government, food industries and health organisations to address high salt intake in the population.

Necessity of a systematic annual consultation in primary care to better improve detection and control of hypertension?

BACKGROUND: In 2015, more than 11 million patients treated for arterial hypertension in France. According to several studies in the general population, about 50% of hypertensive subjects are treated and about 20% are treated and controlled. There is very few data in general medicine. Our work has studied how hypertension control may have differed in general medicine. METHODS: A cross-sectional observational study was carried out in a rural health centre (Domfront, Normandy, France) on subjects aged 40 to 65 years in 2018. A subject was considered to be hypertensive if his blood pressure (taken in the office in routine care) was greater than 140/90 or if it was treated with antihypertensive drugs. OUTCOMES: Of 1,925 subjects, there were 54.3% women, aged 54.6 ± 7.1 years. The mean blood pressure was 127 ± 13/76 ± 8 mmHg, 60.6% (682/1,127) were overweight and 5.0% (96/1,925) were diabetic. 646 (33.6%) were hypertensive and 410 hypertensive (63.5%) were treated. 39.0% (252/646) were treated and controlled. DISCUSSION: In general medicine, blood pressure control seems to be better than in the general population, whereas the general practitioner is often the first contact with the healthcare system. Poor blood pressure control in the general population can be explained by the lack of general medicine consultation for untreated hypertensive subjects. A systematic annual consultation in general practice could be proposed for this specific population.

LRP1 Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases.

BACKGROUND: Genome-wide association studies implicate common genetic variations in the LRP1 (low-density lipoprotein receptor-related protein 1) locus at risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown. METHODS: Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells were genome-edited using CRISPR-Cas9 to delete or modify candidate enhancer regions and generate LRP1 knockout cell lines. Cells were differentiated into smooth muscle cells through a mesodermal lineage. Transcription regulation was assessed using luciferase reporter assay, transcription factor knockdown, and chromatin immunoprecipitation. Phenotype changes in cells were conducted using cellular assays, bulk RNA sequencing, and mass spectrometry. RESULTS: Multitrait colocalization analyses pointed at rs11172113 as the most likely causal variant in LRP1 for fibromuscular dysplasia, migraine, pulse pressure, and pulmonary function trait. We found the rs11172113-T allele to associate with higher LRP1 expression. Genomic deletion in induced pluripotent stem cell-derived smooth muscle cells supported rs11172113 to locate in an enhancer region regulating LRP1 expression. We found transcription factors MECP2 (methyl CpG binding protein 2) and SNAIL to repress LRP1 expression through an allele-specific mechanism, involving SNAIL interaction with disease risk allele. LRP1 knockout decreased induced pluripotent stem cell-derived smooth muscle cell proliferation and migration. Differentially expressed genes were enriched for collagen-containing extracellular matrix, connective tissue development, and lung development. LRP1 knockout and deletion of rs11172113 enhancer showed potentiated canonical TGF-ß (transforming growth factor beta) signaling through enhanced phosphorylation of SMAD2/3. Analyses of the protein content of decellularized extracts indicated partial extracellular matrix remodeling involving enhanced secretion of CYR61, a known LRP1 ligand involved in vascular integrity and TIMP3, implicated in extracellular matrix maintenance and also known to interact with LRP1. CONCLUSIONS: Our findings support allele-specific LRP1 gene repression by the endothelial-to-mesenchymal transition regulator SNAIL. We propose decreased LRP1 expression in smooth muscle cells to remodel the extracellular matrix enhanced by TGF-ß as a potential mechanism of this pleiotropic locus for vascular diseases.

Association of Anticoagulant Use With Hemorrhage Location and Etiology in Incident Spontaneous Intracerebral Hemorrhage.

BACKGROUND: It is unknown whether hypertensive microangiopathy or cerebral amyloid angiopathy (CAA) predisposes more to anticoagulant-associated intracerebral hemorrhage (AA-ICH). The purpose of our study was to determine whether AA-ICH is associated with lobar location and probable CAA. METHODS: This was a cross-sectional analysis of patients with first-ever spontaneous ICH admitted to a tertiary hospital in Boston, between 2008 and 2023. Univariable and multivariable logistic regression were used to investigate the association between anticoagulation use and both lobar hemorrhage location and probable CAA on magnetic resonance imaging (MRI) by Boston Criteria 2.0 or computed tomography by Simplified Edinburgh Criteria. RESULTS: A total of 1104 patients (mean [SD] age, 73 [12]; 499 females [45.0%]) were included. Of the 1104 patients, 268 (24.3%) had AA-ICH: 148 (55.2%) with vitamin K antagonists and 107 (39.9%) with direct oral anticoagulants. Brain MRI was performed in 695 (63.0%) patients. The proportion of patients with lobar hemorrhage was not different between those with and without AA-ICH (121/268 [45.1%] versus 424/836 [50.7%]; odds ratio [OR], 0.80 [95% CI, 0.61-1.05]; P=0.113). Patients with AA-ICH were less likely to have probable CAA on MRI (17/146 [11.6%] versus 127/549 [23.1%]; OR, 0.44 [95% CI, 0.25-0.75]; P=0.002) and probable CAA on MRI or computed tomography if MRI not performed (27/268 [10.0%] versus 200/836 [23.9%]; OR, 0.36 [95% CI, 0.23-0.55]; P<0.001). Among patients with AA-ICH, there were no differences in the proportion with lobar hemorrhage (63/148 [42.6%] versus 46/107 [43.0%]; OR, 1.02 [95% CI, 0.62-1.68]; P=0.946) or probable CAA on MRI (10/72 [13.9%] versus 7/69 [10.1%]; OR, 0.70 [95% CI, 0.25-1.96]; P=0.495) between vitamin K antagonists and direct oral anticoagulant users. CONCLUSIONS: AA-ICH was not associated with lobar hemorrhage location but was associated with reduced odds of probable CAA. These results suggest that hypertensive microangiopathy may predispose more toward incident AA-ICH than CAA and emphasize the importance of blood pressure control among anticoagulant users. These findings require replication in additional cohorts.

Standards for the Implementation, Analysis, Interpretation, and Reporting of 24-hour Ambulatory Blood Pressure Monitoring Recommendations of the Italian Society of Hypertension.

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is recognized as a reference tool for accurately diagnosing hypertension. Until a few years ago, this technique was restricted to use by specialists. Recently, however, due to the need for wider availability and thanks to technological innovation, simplification of analysis processes, and increasing recognition of the importance of this tool for the diagnosis of hypertension, ABPM is now also being used in non-specialist settings. In such settings, ABPM is used with a two-pronged approach: (i) independently by a general practitioner with the possibility of specialist supervision for particular and complex cases; (ii) in the non-medical setting (community pharmacies, home care services, etc.) where the healthcare provider is trained in the proper use of the technique, with the understanding a physician must be responsible for the final clinical reporting. Unfortunately, due to the increasingly wide diffusion of ABPM, there has been considerable confusion about management roles and responsibilities in recent years. To clarify competencies and roles and standardize the processes related to the technique's implementation and proper management, experts of the Blood Pressure Monitoring Working Group of the Italian Society of Hypertension have drafted this document with the aim of providing a quick and easy reference guide for training healthcare professionals in the field.

Sacubitril/valsartan reduces proteinuria depending on blood pressure in patients with stage 4-5 chronic kidney disease.

BACKGROUND: Blood pressure (BP) control is an important factor in the management of chronic kidney disease (CKD). Several studies have shown that BP in many patients with CKD remained uncontrolled even with multiple medications. Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), has been newly approved for treating hypertension in Japan. However, the renoprotective effects remain unclear, particularly in patients with advanced CKD. Here, we investigated the effects on proteinuria of this ARNI in patients with stage 4-5 CKD. METHODS: We retrospectively collected data from outpatients with stage 4-5 CKD who started ARNI from January until December 2023. The primary outcome was the change in urine protein creatinine ratio (UPCR) at 6 months after ARNI initiation. Secondary outcomes were systolic and diastolic BP, estimated glomerular filtration rate (eGFR), serum potassium, and serum uric acid (UA). We analyzed factors associated with 50% UPCR reduction by multivariate analysis. RESULTS: In total, 47 patients were analyzed. ARNI reduced UPCR from 2.14 g/gCr (interquartile range; 1.09-2.91) to 1.05 g/gCr (0.42-1.95; p < 0.001). Systolic BP fell from 150.0 mmHg (139.5-160.0) to 134.0 mmHg (124.5-140.0; p < 0.001). No significant changes in eGFR, serum potassium, and serum uric acid were observed, except for a slight decrease in eGFR among patients with conversion from a renin-angiotensin system inhibitor to ARNI. In multivariate regression analysis, higher systolic BP (per 10-mmHg increase) was significantly associated with reduced proteinuria (odds ratio 2.51, 95% confidence interval 1.35-4.66; p = 0.004). CONCLUSIONS: ARNI reduced proteinuria in patients with stage 4-5 CKD, particularly for those with uncontrolled hypertension.

Association of Hyperandrogenaemia With Hypertension and Cardiovascular Events in Pre-menopausal Women- A Prospective Population-Based Cohort Study.

OBJECTIVE: The present study aimed to clarify the conflicting association of premenopausal hyperandrogenaemia (HA) with the development of hypertension and CVDs in women. DESIGN: A population-based cohort study including 5889 women. METHODS: The association of serum testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index (FAI) at age 31 with blood pressure (BP) and hypertension (BP ≥140/90 mmHg and/or use of antihypertensive medication) at ages 31 and 46 and with CVDs (angina pectoris [AP] and/or acute myocardial infarction [AMI] n=74, transitory cerebral ischemia [TIA] and/or stroke n=150) and combined CVD events (AP, AMI, stroke, heart failure, or CVD mortality n=160) by age 53 was investigated. RESULTS: T and FAI were positively associated with systolic and diastolic BP at ages 31 and 46 in the multivariable model. Compared to their lowest quartile, the highest quartiles of T and FAI were positively associated with hypertension at age 31 in the multivariable model. During the 22-year follow-up, FAI was positively associated with increased risk of AP/AMI (hazard ratio [HR]:2.02, 95%CI:1.06-3.85) and overall CVD events or mortality (HR:1.54, 95%CI:1.02-2.33) in the unadjusted models. However, the significance disappeared after adjusting for BMI. CONCLUSIONS: Women with HA at premenopausal age had an elevated risk of hypertension, and together with BMI, increased risk of CVD events and CVD mortality during the 22-year follow-up. However, because of several study limitations regarding ethnicity and BMI characteristics, a longer follow-up of this cohort and future studies in ethnically diverse populations are needed to verify the results.