Clinical Research Directory

Cardiovascular Manifestations of MR Activation in Primary Aldosteronism: Pilot Clinical Study

This research study aims to learn more about the impact the hormone aldosterone on the heart. Primary aldosteronism is a condition where the body's adrenal glands make too much of the hormone aldosterone, which can cause high blood pressure and increase the risk of heart and kidney disease. Treatment with medications that block aldosterone can reduce that risk. This study is trying to learn whether treatment with a medication that blocks aldosterone can improve heart function in people who make too much aldosterone.

Community Park-Based Programs for Health Promotion: Active Older Adults Prospective Cohort Study

The Active Older Adults prospective cohort study examines the effects of a park-based fitness program on cardiovascular fitness outcomes for older adults (aged 50 years and older). Duke will perform a secondary analysis of the data collected as part of the Active Older Adults prospective cohort study run by Miami-Dade County Parks and Recreation.

E3 Hypertension - A Team-based, Multidisciplinary Model in Addressing Barriers to Hypertension Control

This study aims to compare a multidisciplinary clinical hypertension and social needs intervention to enhanced standard of care for hypertension management in primary care clinics with regards to hypertension control outcomes.

Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study (GENE-FORECAST)

Our objective is to develop a community-based cohort and novel genomic science resource for defining the biological significance of ancestry-related genomic variation in African-Americans within the GENE-FORECAST :GENomics, Environmental FactORs and the Social DEterminants of Cardiovascular Disease in African Americans STudy. AIM I. examine the associations between common or ancestry-related DNA variants and CVD risk factors (e.g. hypertension) and phenotypes (e.g. coronary artery calcification) in African-Americans (AA).AIM II. To examine the associations between health behaviors or social-environmental factors and CVD risk factors and phenotypes in AA.The study is designed to create a cohort amenable to nested case-control analyses based on a community-based sampling frame with a target size of approximately 1800 self-identified, US -born, African-American (AA) men and women (ages 21-65) to be recruited over the next 5-6 years from the metropolitan Washington DC, Montgomery County (MC) and Prince George s County (PG) areas to be recruited to the NIH Clinical Center. The initial participant recruitment two approaches: 1) a random-digit telephone screening survey targeting study-eligible AA that will be consented and invited to an evaluation visit in the NIH Clinical Center which we contracted with a well-established survey group (Southern Research Group \[SRG\]); and 2) a community outreach effort to recruit participants into the Clinical Center by leveraging marketing and the engagement of community-based leaders, organizations and faith-based institutions in the area. this approach will yield a sample with normal individuals as well as a high proportion of AA with CVD risk factors such as obesity and hypertension that predispose to the eventual clinical signs and symptoms of CVD (e.g. heart attack and stroke). it is anticipated that the prevalence of clinically manifest CVD (history of angina, heart attack or stroke) will be less than 10-15% of the sample. All will medical evaluation (e.g. anthropometrics, blood pressure), laboratory tests (e.g. lipid levels, kidney function), social determinants profiles (e.g. socioeconomic status (SES), perceived stress, discrimination, depression, perceived neighborhood characteristics), blood/urine collection for deep-sequencing based omic analyses (e.g. whole exome sequencing, and RNA-Seq), as well as testing for pre-clinical , biomarkers of the pathobiological processes of CVD or CVD phenotypes (e.g. coronary artery calcification, microalbuminuria, leukocyte telomeres, or vascular dysfunction). It is anticipated that these deep sequencing efforts will yield novel ancestry-related DNA variants associated with the CVD phenotypes; yet with unclear biological significance in elucidating racial disparities in CVD. Accordingly, our protocol also includes a Genotype-to-Phenotype (G2P) component that re- contacts subsets of the cohort based on their genotype (e.g. APOL1 chronic kidney disease risk alleles) for a call-back visit for more in-depth phenotyping and characterization of the potential effect of the DNA variant of interest on human systems biology. In some cases family members of the proband may also be invited to participate in these G2P studies to further characterize the biological significance of these putative functional DNA variants of interest. The primary outcome variables involve well established CVD phenotypes: 1) CVD risk factors (e.g. hypertension, dyslipidemia), 2) markers of pre-clinical CVD (i.e. coronary artery calcification, coronary plaque burden by cardiac CT angiography (CTA), carotid plaque burden by 3D ultrasound, vascular dysfunction, microalbuminuria, C-reactive protein, Vitamin D levels). The protocol will assess exposures associated with CVD and relevant covariates including: 1) social determinants (e.g. socioeconomic status (SES), perceived stress, discrimination, and depression); 2) environmental factors such as neighborhood characteristics (geospatial features of healthy lifestyles \[e.g. walkability\]) and 3) behavioral factors (e.g. diet, physical activity). The G2P callback visit protocol will involve additional measures of in-depth phenotyping that include: 1) peripheral immune cell phenotyping (e.g. T-cell, monocyte subsets); 2) blood/immune cell RNAseq; 3) iPSC cell line generation (endothelial; vascular smooth muscle cells) and analysis of cardiovascular cell systems biology; 4) HDL proteome analysis, 5) FDG PET/CT and/or PET/MRI scan (vascular inflammation) 6) echocardiography, 7) bisulfite sequencing for identifying sites of DNA methylation, and 8) chromatin immunoprecipitation followed by sequencing (Chip-Seq) for identifying sites of histone modification. It is anticipated that this multi-level, multi-dimensional analysis of genomic and phenotypic characteristics of AA will advance our understanding of the bio-social determinants of the intragroup variance and the increased overall burde...

Study of Efficacy and Safety of Tonlamarsen in Participants With a Recent Hospitalization and a Concurrent Episode of Acute Severe Hypertension

The purpose of this study is to evaluate the blood pressure-lowering effect of tonlamarsen in adult participants who were recently hospitalized and concurrently experienced an episode of acute severe hypertension.

Zilebesiran in Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease

The purpose of this study is to evaluate whether zilebesiran versus placebo reduces the risk of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events. This is an event-driven study that will continue until the targeted number of positively adjudicated primary endpoint clinical outcome events (COEs) have been reached.

Comparing Hypertension Remote Monitoring Evaluation Redesign

The goal of this clinical trial is to compare the effectiveness of evidence-based, adapted, and tailored, patient-focused and clinic-focused strategies to improve blood pressure (BP) control in English- and Spanish-speaking patients with hypertension (HTN).

Evaluation of MTHFR Gene Polymorphism and Periodontal Clinical Parameters in Healthy, Hypertensive, and Periodontitis Individuals

This observational study aims to evaluate the relationship between MTHFR gene polymorphisms and periodontal clinical findings in healthy individuals, individuals with hypertension, individuals with periodontitis, and individuals with both hypertension and periodontitis. A total of 200 participants will be included in four groups of 50 participants each. Periodontal clinical measurements, including plaque index, gingival index, bleeding on probing, probing depth, and clinical attachment level, will be recorded. Venous blood samples will be collected for DNA isolation and analysis of MTHFR gene polymorphisms. The study will investigate whether MTHFR gene polymorphisms are associated with periodontal clinical parameters and hypertension.

SPIRO-First: A Pragmatic Primary Care-Embedded Pilot Trial of Renin-Guided First-Line Antihypertensive Therapy

The goal of this clinical trial is to determine whether a renin-guided antihypertensive treatment strategy is feasible to implement in community primary care clinics and to explore whether spironolactone improves blood pressure control in adults with low-renin hypertension. The main questions it aims to answer are: Is it feasible to identify, recruit, randomize, and follow adults with low-renin hypertension in a pragmatic primary care-based clinical trial? Does first-line treatment with spironolactone result in greater reductions in ambulatory blood pressure compared with standard first-line antihypertensive therapy among adults with low-renin hypertension? Researchers will compare spironolactone 25 mg daily with standard first-line antihypertensive therapy (candesartan, hydrochlorothiazide, or amlodipine) to determine whether spironolactone provides better blood pressure control in adults with low-renin hypertension. Participants will: Undergo blood pressure assessments, blood tests, and ambulatory blood pressure monitoring (ABPM) to determine eligibility. Be randomly assigned to receive either spironolactone or a standard first-line antihypertensive medication for 12 weeks. Complete follow-up visits and laboratory testing to monitor blood pressure response, kidney function, electrolyte levels, medication adherence, and side effects. Undergo repeat blood pressure measurements and ABPM at the end of the study.

Randomized Clinical Trial to Improve Mobility After Hospitalization

The objective of this study is to test the feasibility of using behavioral economic interventions (gamification with social incentives) to increase physical activity after hospital discharge to reduce incident mobility disability among older adults.

EASi-PROTKT™ - A Study to Test Vicadrostat (BI 690517) Taken Together With Empagliflozin in People With Type 2 Diabetes, High Blood Pressure, and Cardiovascular Disease

This study is open to adults with type 2 diabetes, high blood pressure, and cardiovascular disease. People can join the study if they have these conditions and do not have a history of heart failure. The purpose of this study is to find out if a medicine called vicadrostat, when taken with empagliflozin, helps reduce cardiovascular risk in people with these conditions. The study will compare this combination to a placebo version of vicadrostat with empagliflozin. Participants are put into 2 groups randomly, which means by chance. One group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets with empagliflozin. Placebo tablets look like vicadrostat tablets but do not contain any medicine. Participants take a tablet once per day for 2 and a half years and up to 4 years and 3 months. All participants also continue their medication for type 2 diabetes, high blood pressure, and cardiovascular disease. Participants have an equal chance of receiving the study medicine or placebo. Participants are in the study for up to 4 years and 3 months. During this time, they visit the study site regularly. During these visits, doctors collect information about participants' health and take blood samples. The doctors document when participants experience cardiovascular events. The doctors also regularly check participants' health and take note of any unwanted effects.

WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)

Background: Williams Syndrome (WS) is a genetic disorder. People with WS have less of a protein that allows parts of the body to stretch than other individuals. Researchers are interested in the stretchiness of the skin of people with WS and how it may relate to cardiovascular problems some people with WS develop. They are also interested in identifying exposures such as medications that may change the elasticity of the skin and vessels. Objective: To learn more about the skin and blood vessels in individuals with WS and how those tissues change over time. Eligibility: People ages 5-70 with WS. People ages 1-70 with a medical condition that affects connective tissue. Design: Participants will be screened with a review of their medical records. Participants will have 1 visit. Participants with WS may do so at a Williams Syndrome Association family meeting or camp, or at NIH. Other participants will be seen at NIH. During the visit, participants will have height, weight, and blood pressure measured. Researchers will listen to the participant s chest and abdomen. Participants skin will be examined. It may be photographed. Participants will have photos of their eyes and face taken. Researchers will use a DermaLab Suction Cup Probe. A small suction cup will be placed on the arm with a sticker. It will pull lightly on the skin. This allows a computer to measure skin flexibility. Researchers will use a SphygmoCor. A probe that looks like a dull pencil will be placed on the wrist, neck, and groin area. A computer will measure how fast the pulse is moving and will estimate blood vessel flexibility. Participants may be invited to have these procedures repeated at a later date (2 years from now or more).

A Multi-centre Study Evaluating the Performance and Acceptance of the Hilo Band Cuffless Blood Pressure Medical Device in the Normo-, Hypo- and Hyper-tensive Young Population: a Comparison With the 24-h Ambulatory Blood Pressure Monitoring (ABPM)

Hypertension is one of the main risk factors for the onset of cardiovascular diseases. It is often silent, and most individuals are unaware they have it. The 24-hour Ambulatory Blood Pressure Monitoring (24-hour ABPM) device allows for continuous blood pressure (BP) monitoring over a 24-hour period and is currently considered the gold standard for diagnosing hypertension. However, it is expensive, time-consuming for healthcare personnel, bulky, and often uncomfortable to wear-especially during the night. Recently, other BP monitoring devices have entered the market. One of them is the Aktiia bracelet, renamed as Hilo band as of 8 april 2025, (Hilo band SA, Neuchâtel, Switzerland), CE-marked, which estimates BP and heart rate using a pulse wave analysis (PWA) technique. Hilo band is non-invasive, comfortable to wear, and allows for long-term BP monitoring. Especially in adolescents, BP monitoring might present a special challenge due to high physical activity and often low compliance. Wearable technologies like Hilo band could offer an interesting alternative to the traditional 24-h ABPM. Results in young active adults and adolescents might be different comparing between Hilo and the 24-h ABPM and need to be assessed. Furthermore, adolescents often dislike the 24-h ABPM beacuse of the discomfortable BP cuff (specially during the night) and the stigmatic effect of the 24-h ABPM at school/work. To conclude, there is a need especially in young people of comfortable, precise and user-friendly technique for long term BP measurement and monitoring. However, there is insufficient data to support the use of Hilo band in healthcare settings for the diagnosis and monitoring of hypertension. In one study, Hilo band was compared to the 24-hour ABPM only for daytime BP readings in a population enrolled in a cardiac rehabilitation program, and thus was not tested in apparently 'healthy' individuals who may be hypertensive. Another study assessed Hilo band's performance compared to double auscultation in older adults aged 65 to 85 years in different body positions (sitting, standing, and lying down); therefore the young population and adolescents were not considered. In our research project, we aim to evaluate the performance of Hilo band compared to 24-hour ABPM in a young population (including adolescents), considering both daytime and nighttime blood pressure measurements.

Clinical and Molecular Characteristics of Primary Aldosteronism in Blacks

Background: The adrenal gland makes the hormone aldosterone. This helps regulate blood pressure. An adrenal gland tumor that makes too much aldosterone can cause high blood pressure and low potassium. The cause of these tumors is unknown, but sometimes they are inherited. Objective: To study the genes that may cause primary aldosteronism in Black individuals. Eligibility: People ages 18-70 who: Are Black, African American, or of Caribbean descent And have difficult to control blood pressure or primary aldosteronism Relatives of people with primary aldosteronism Design: Participants who are relatives of people with primary aldosteronism will have only 1 visit, with medical history and blood tests. Participants with primary aldosteronism or difficult to control blood pressure (suspected to possibly have primary aldosteronism) will be screened with a 1-2 hour visit. If they qualify, they will return for a hospital stay for 7-10 days. Tests may include: Medical history Physical exam Blood tests: Participants will have a small tube (IV catheter) inserted in a vein in the arm. They may drink a glucose-containing liquid or get a salt solution. If medically indicated, they may have invasive blood tests with a separate consent. Urine tests: Some require a high-salt diet for 3 days. Heart tests Scans: Participants lie in a machine that takes pictures of the body. A dye may be injected through a vein. Small hair sample taken from near the scalp. Kidney ultrasound Bone density scan: Participants lie on a table while a camera passes over the body. If the doctors feel it is medically necessary, they will offer participants treatment depending on their results. These treatments may cure the patient of their disease and may include: 1. Having one adrenal gland removed by the Endocrine surgeon under anesthesia. Patients will have follow-up visits 2-4 weeks after surgery. 2. Taking drugs to block the effects of aldosterone Participants may return about 1 year later to repeat testing.

Sympathetic Activity in Post-injury Outcomes: Impact on Sleep and caRdiovascular Health InvesTigation

The goal of this observational study is to learn about the long-term health of United States military service members who were injured during combat. The main questions it aims to examine are: * How does the severity of a combat injury impact 1) cardiovascular risk, 2) the sympathetic nervous system and arrhythmias, 3) blood pressure, and 4) sleep disorders? * Are self-reported mental health symptoms related to sympathetic nervous system hyperactivity, sleep disorders, and cardiovascular risk in combat-injured service members? This study will recruit from a sample of participants in another research study called the Wounded Warrior Recovery Project (WWRP) who 1) agreed to be contacted about future research studies and 2) have a record of a combat injury within the Injury Severity Score ranges required for this study. Participants will: * Provide demographic information and a medical history review * Visit a local laboratory for biometrics measurements and to provide blood and urine samples * Wear an ambulatory electrocardiogram monitor for 24 hours per day for seven consecutive days * Wear a home sleep test monitoring device for one night * Wear a blood pressure monitor for 24 consecutive hours on the day after the home sleep test At the end of the study, participants will be asked to mail back the home sleep test and blood pressure monitors. Prepaid package materials will be provided.

A Cardiometabolic Health Program Linked With Clinical-Community Support and Mobile Health Telemonitoring to Reduce Health Disparities

The LINKED- HEARTS Program is a multi-level project that intervenes at the practice level by linking home blood pressure monitoring (HBPM) with a telemonitoring platform (Sphygmo). The program incorporates team-based care by including community health workers (CHWs) and pharmacists to improve the outcomes of multiple chronic conditions (reduced blood pressure (BP), lower blood sugar, and improved kidney function). The LINKED-HEARTS Program will recruit a total of 600 adults with uncontrolled hypertension (BP ≥ 140/90 mm Hg) AND either type 2 diabetes or chronic kidney disease (CKD) across 16 community health centers or primary care practices serving high-risk adults. This cluster-randomized trial consists of two arms: (1) enhanced "usual care arm," wherein patients will be provided with Omron 10 series home BP monitors and will be managed by the patients' primary care clinicians as usual; and (2) the "intervention arm" which will integrate HBPM telemonitoring, a CHW intervention and provider-level interventions into the usual clinical care to improve BP control and provide support for self-management of chronic conditions. The study pharmacist will conduct telehealth, use the Sphygmo app and the Pharmacist Patient Care Process to collaborate with other providers to optimize pharmacologic therapy to improve hypertension outcomes and with payors to ensure consistent access to drug therapy.

Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID)-2.0

Background: \- High blood pressure is a common problem. It can cause heart attacks, strokes, and kidney failure. It affects African Americans more than other racial groups. Data were collected from over a thousand African Americans across the country. The data were put into a database (MH-GRID). The data were about genes, diet, sleep, body mass index. They also cover stress and access to healthy foods and parks. Researchers at NIH will study these data in new ways. They want to learn more about the connection between African Americans and high blood pressure. Objective: \- To study MH-GRID data to find the causes of severe high blood pressure and other cardio-metabolic problems in people of African ancestry. Eligibility: \- African Americans age 30 55 with severe high blood pressure were used in the MH-GRID study. No new participants will be enrolled in this study. Design: \- Researchers will examine data from the MH-GRID study.

Antihypertensive Self-titration in US Primary Care

The objective of this study is to pilot test self-titration intervention procedures. We are testing a new way to manage high blood pressure from home. In this study, patients will check their blood pressure at home and take steps to adjust their blood pressure medications if needed, following a plan outlined with a primary care doctor. Participation in this study will last up to 6 months. Participation will include a research visit to review the blood pressure management process. A primary care provider will also develop a medication plan for each participant to follow during the study and address any questions at their upcoming visit. During the study, each participant will be asked to check their blood pressure at home every day for 1-2 weeks a month using a study-provided blood pressure cuff. They will be asked to follow a set of instructions to request a medication change from their provider, based on their blood pressure readings. Participation may also include lab visits and additional visits with a primary care physician before making medication changes, if needed. There will also be a follow-up visit within 6 months.

Tracking Income Dynamics and Everyday Health Study

Among adults with chronic illnesses like hypertension, diabetes, or HIV, adherence to daily oral medications is essential but often below 50%. Why do medication adherence and preventive health service engagement remain stubbornly low? Scarcity theory offers a novel explanation in the context of poverty. It posits that economic hardship imposes a cognitive burden that shifts attention from long-term goals to immediate needs, reduces future orientation (the relative value placed on immediate vs. future outcomes), and limits mental bandwidth (the cognitive resources needed for decisions), thus undermining behaviors like daily medication adherence and service engagement. To address these gaps, the study's objective is to rigorously test whether and how economic scarcity affects medication adherence and preventive service uptake among older adults with chronic disease, leveraging the naturally occurring monthly fluctuation in scarcity created by the Supplemental Nutrition Assistance Program (SNAP) benefit cycle as a natural experiment. There are three aims: 1. Daily medication adherence will be measured objectively for four months with wireless electronic pill bottle caps (CleverCaps). The investigators will test whether, when, and by how much adherence changes as scarcity fluctuates during the SNAP benefit cycle. 2. The investigators will conduct two easily implementable RCTs to test whether scarcity affects participants' engagement with beneficial services requiring navigation of administrative burdens. In one trial, participants will be randomized to receive an invitation during either a high- or low- scarcity period (i.e., before vs. after SNAP receipt) to a personalized preventive health review that identifies gaps in US Preventive Services Task Force Grade A/B recommendations. In the second, participants will be invited to free financial counseling provided by the City of Philadelphia during a high- or low-scarcity period. The investigators hypothesize invitation response rates will be \>15% higher during low-scarcity periods. 3. Potential mechanisms that link scarcity with health behaviors will be examined by randomizing timing of validated measures of mental bandwidth and future orientation during a period of high- or low-scarcity (i.e., before vs. after SNAP receipt). The investigators hypothesize that there will be differences in several measures between participants who are randomly assessed during high- vs. low-scarcity periods (i.e. before vs. after SNAP receipt). Impact: Demonstrating that scarcity helps to explain low medication adherence and beneficial health-related service uptake can inform patient-centered adherence interventions, clinical care-delivery approaches, health-system strategies, and public health approaches to improve these health behaviors and promote healthy aging.

Polygenic Risk Score Implementation and Stratification for Managing Blood Pressure

In a multi-ethnic population, a genome-wide polygenic risk score (PRS) for systolic blood pressure (SBP), incorporating over one million common genetic variants, predicts blood pressure (BP) traits and the risk of adverse cardiovascular events beyond traditional risk factors. Delivering SBP PRS information to young and middle-aged adults with hypertension (HTN) and poor cardiovascular health (CVH) may enhance their motivation to adopt healthier lifestyles, improve blood pressure control, and ultimately reduce the risk of future cardiovascular disease (CVD). This randomized controlled trial will assess the impact of SBP PRS disclosure and theory-based genomic counseling on systolic blood pressure and health behaviors. A total of 300 adults aged 18-55 years will be enrolled and randomized to receive either routine clinical care or SBP PRS results with structured genomic counseling based on the Health Belief Model (HBM). Participants will be followed for 12 months. The primary outcome is change in 24-hour mean SBP from baseline to one year. Secondary outcomes include changes in physical activity, diet, medication adherence, smoking, lipid and glucose levels, and body composition. The study will also evaluate how behavior change is influenced by health beliefs, including perceived risk and self-efficacy. This study aims to advance the use of genomic tools in hypertension management and cardiovascular disease prevention.

Preparing FIM-BCS - A Lifestyle Modification for African-American Breast Cancer Survivors

Hypertension and obesity are both major risk factors for cardiovascular disease (CVD), a leading cause of death for Black women in the United States. The investigators propose examining the feasibility and acceptability of the 12-week RN-CHeFRx (Real Nourishment and Cooking Healthy Food is Rx) intervention \- grocery delivery, cooking classes, and nutrition education - for Black women with hypertension and obesity to improve nutritious eating habits and blood pressure control.

Evaluation of an Integrated, Digital, Nurse-led, Remote Monitoring Care Pathway for Cardiovascular Risk Management

The goal of this observational study is to evaluate the implementation of a structured, digital, nurse-led, remote monitoring care pathway for cardiovascular risk management (CVRM). Participants will receive this care as part of routine clinical practice. In addition to standard follow-up, participants will complete questionnaires on quality of life, medication adherence, system usability, and patient satisfaction.

MASLD in Type 2 Diabetes in Primary Care - a Follow-up Study

The goal of this observational study is to understand how metabolic dysfunction-associated steatotic liver disease (MASLD) changes over time in individuals with type 2 diabetes who previously participated in the EPSONIP study. The main questions it aims to answer are: 1. How common are MASLD and advanced liver fibrosis at long-term follow-up? 2. Which factors are associated with progression or regression of liver fat accumulation and liver fibrosis over time? Participants will: * Undergo a clinical examination and review of medical history. * Provide blood, urine, and biobank samples. * Undergo liver assessment using vibration-controlled transient elastography (VCTE). * Undergo magnetic resonance imaging (MRI) to assess liver fat, liver fibrosis, and body composition. * Complete questionnaires regarding lifestyle and physical activity. * Undergo physical activity measurements using accelerometers and additional assessments related to blood pressure and sleep apnea.

Addressing HyperteNsion and Diabetes Through Community-Engaged Systems in Puno, Peru (ANDES Study)

Hypertension (HTN) has become the largest driver of morbidity and mortality (M\&M) worldwide, affecting nearly 1 billion persons, the vast majority living in low- and middle-income countries (LMICs). While clinical research has identified highly-efficacious and inexpensive options to control HTN, rates of awareness, treatment and control of HTN are abysmally low. Implementation strategies that can effectively reach and engage patient populations while feasible within the constraints of frail health systems are urgently needed. In Peru, less than 10% of those with HTN are optimally controlled and thus avoidable M\&M continues to increase at unacceptable levels. In the proposed ANDES strategy, ANDES research team will study a vulnerable, impoverished indigenous Andean population that has a high prevalence of HTN (18.5%) and Type 2 Diabetes (T2D) (7.4%); living at high altitude. The study has two phases: UG3/UH3. During the formative UG3 phase (ended 12/31/22) we completed 3 aims, including: a) adapting community-based service delivery models for detection/control of HTN/T2D using stakeholder-engaged approaches; and b) assessed short-term implementation and service outcomes of pilot Health Fairs to detect HTN/T2D and a CHW-led model for engagement and treatment of HTN/T2D in two communities. A number of stakeholder in-depth interviews revealed significant limitations to HTN control. Discrete Choice Experiments (DCEs) surveys helped understand attributes for a community health worker (CHW)-led HTN care program that patients would value. Human-Centered Design was used to refine CHWs manual prototype, frequency and content of training sessions on patients, training CHW, supervision and integration into the healthcare system; facility-based health worker training content and approaches; identified opportunities for CHWs to improve health care system by helping to promote hypertension diagnosis, treatment and control. All these activities were used to refine the protocol that was tested in the pilot study where 1,079 subjects underwent blood pressure monitoring under a Standard Operating Procedure using electronic tablets to construct a REDCap database. The UH3 phase will test the adapted ANDES strategy. ANDES is a two-arm, individually randomized superiority trial with parallel assignment. The overall objective of ANDES is to evaluate the effectiveness of a home-based Health Agent-led intervention in reducing blood pressure and improving diabetes control in patients from under-resourced communities in Puno, Peru. Potential ANDES study participants will be identified, screened, and recruited via 2 different mechanisms: 1) community health fairs and 2) healthcare facility-based enrollment. Health fair planning, will be conducted in collaboration with DIRESA \& EsSalud and local healthcare facility leaders. All health fair attendees will be screened for blood pressure measurements. ANDES research study staff will do screening at tents in the health facilities after doctors refer patients (or for any patients to visit who want) to inquire about their willingness for an in-person screening visit at their home. Recruitment will be rolling over 24 months during which 1068 participants in total (534 participants per arm) will be enrolled. To detect a difference in systolic blood pressure of 2.5 mmHg between intervention and control arms with 95% confidence, 90% power and a standard deviation of 12 mmHg, ANDES research team would need 485 participants per arm. Assuming a conservative lost-to-follow-up of 10% at 12 months, ANDES research team would need to randomize 1068 participants in total (534 participants per arm). The primary outcome is to determine if the ANDES intervention impacts SBP in comparison to the usual care arm 12 months after randomization. ANDES participants will initiate one of two care pathways according to the randomization assignment. Participants in the usual care group will be referred to their local healthcare facility for evaluation and/or to receive medical therapy per typical standard of care and at the discretion of the treating physician for the entirety of the ANDES study. Participants in the ANDES intervention group will receive the ANDES implementation package consisting of health agent home visits for 12 consecutive months. Implementation package delivery will end after month 12, at which time intervention participants will be advised to obtain standard care from their local healthcare facility. Study outcome measures will be obtained in both the usual care and ANDES intervention group at months 12 and 18 post-randomization. All participants will receive visits at baseline, 12 and 18 months for study outcome assessments. Intervention participants will additionally receive a total of 12 visits by health agents as part of the intervention package, for a total of 18 visits for those assigned to the intervention group.