1. Age 55-79, all races/ethnicities, and both women and men are eligible; 2. Mini-mental state exam (MMSE) > 26 to exclude cognitive impairment or dementia; 3. Healthy normotensive subjects (24-hour ambulatory BP<125/75 mmHg without use of antihypertensive medication); 4. Patients with hypertension defined as 24-hour SBP ≥130 mmHg , patients on BP medications are eligible; 5. Patients with hypertension are willing to be randomized into either treatment group and ability to return to clinic or laboratory for follow-up visits over 12 months; 6. Fluency in English, adequate visual and auditory acuity to allow neuropsychological testing; 7. Screening laboratory tests and ECG without significant abnormalities that might interfere with the study 1. History of stroke, transient ischemic attack, traumatic brain injury or severe cerebrovascular disease by clinical diagnosis or past MRI/CT; 2. Diagnosis of AD or other type of dementia and neurodegenerative diseases; 3. Evidence of severe depression or other DSM-V Axis I psychopathology 4. Unstable heart disease based on clinical judgment (heart attack/cardiac arrest, cardiac bypass procedures within previous 6 months and congestive heart failure), evidence of atrial fibrillation on ECG, or other severe medical conditions; 5. Chronic kidney diseases with GFR < 40 ml/min; 6. Orthostatic hypotension, defined as standing SBP<100 mmHg; 7. History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis and polymyalgia rheumatica; 8. History of drug or alcohol abuse within the last 2 years; 9. Diagnosis of uncontrolled diabetes mellitus (fasting blood sugar ≥126 mg/dL or A1C >7.5%) 10. Obstructive sleep apnea; 11. Regularly smoking cigarette within the past year; 12. Severe obesity with BMI ≥ 45; 13. Participants enrolled in another investigational drug or device study within the past 2 months; 14. Carotid stent or sever stenosis (> 50%); 15. Pacemaker or other medical device of metal that precludes performing MRI; 16. History of B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable); 17. Any conditions judged by the study investigators to be either medically inappropriate, or risky for participant or likely to have poor study adherence; 18. Claustrophobia; 19. Pregnancy

• Experiments will be performed on 3 groups of nondiabetic human subjects:
• 1) stage I (140-159/90-99 mmHg) subjects with essential hypertension.
• 2) stage I hypertensive subjects with primary aldosteronism
• 3) normotensive controls.
• 1) Any evidence of cardiopulmonary disease, left ventricular hypertrophy or systolic dysfunction by echocardiography.
• 2) Blood pressure averaging ≥160/100 mmHg
• 3) Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2
• 4) Diabetes mellitus or other systemic illness
• 5) Pregnancy
• 6) Hypersensitivity to nitroprusside, phenylephrine, amlodipine or eplerenone
• 7) Any history of substance abuse or current cigarette use
• 8) Any history of psychiatric illness
• 9) History of malignancy

• Women of childbearing potential must not be known to be pregnant or lactating
• Patients must be scheduled for, or have intent to schedule, a screening mammogram
• Patients must be able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol, to be performed at an American College of Radiology Imaging Network (ACRIN)-qualified facility
• Patients must be willing and able to provide a written informed consent
• Patients must not have symptoms or signs of benign or malignant breast disease (eg, nipple discharge, breast lump) warranting a diagnostic rather than a screening mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are eligible as long as other criteria are met
• Patients must not have had a screening mammogram within the last 11 months prior to date of randomization
• Patients must not have previous personal history of breast cancer including ductal carcinoma in situ
• Patients must not have breast enhancements (e.g., implants or injections)
• ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
• To be eligible for inclusion in the annual screening regimen one of the following three conditions must be met in addition to the eligibility criteria above:
• Patients are pre-menopausal; OR
• Post-menopausal aged 45-69 with any of the following three risks factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
• Family history of breast cancer (first degree relative with breast cancer), or, positive genetic testing for any deleterious genes that indicate an increased risk for breast cancer, or
• Currently on hormone therapy; OR
• Post-menopausal ages 70-74 with either of the following two risk factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
• Currently on hormone therapy
• Postmenopausal women are defined as those with their last menstrual period more than 12 months prior to study entry; for the purpose of defining menopausal status for women who have had surgical cessation of their periods, women who no longer have menses due to hysterectomy and oophorectomy will be considered postmenopausal; women who no longer have menses due to hysterectomy without oophorectomy will be considered premenopausal until age 52 and postmenopausal thereafter
• All other postmenopausal women are eligible for inclusion in the biennial screening regimen
• For those women who cannot be assigned to annual or biennial screening at the time of study entry and randomization because they are postmenopausal, have no family history or known deleterious breast cancer mutation, are not on hormone therapy AND have not had a prior mammogram, breast density will be determined by the radiologist?s recording of it at the time of interpretation of the first study screening examination, either DM or TM; for those who are randomized to TM, radiologists will assign BI-RADS density through review of the DM or synthetic DM portion of the TM examination; such women cannot be part of the planned stratification by screening frequency and are expected to represent far less than 1% of the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) population
• Breast density will be determined by prior mammography reports, when available; all other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report

Subjects who meet all of the following criteria are eligible for enrollment into the study:
• Able and willing to give written informed consent and comply with requirements of the study;
• Age ≥18 years-old at the Screening Visit; and
• Elevation of autoantibody anti-cyclic citrullinated peptide-3 (anti-CCP3) defined by result of anti-CCP3 ≥40 units, at Screening. Subjects who meet any of the following criteria are ineligible to participate in the study:
• Evidence of significant retinal disease that, in the opinion of the examiner, would make identification of potential future retinal toxicity from hydroxychloroquine difficult to evaluate;
• A medical history of inflammatory arthritis (IA) of any type and/or rheumatic disease and immunologic disease(s) that may be associated with IA . These diseases include but are not limited to:
• rheumatoid arthritis (RA);
• systemic lupus erythematosus (SLE);
• seronegative spondyloarthropathies;
• inflammatory bowel disease;
• Sjögren's syndrome;
• polymyalgia rheumatic; or
• vasculitis. Note: Crystalline arthropathies are not exclusionary.
• A medical history of:
• congestive heart failure or functional status of New York Heart Association (NYHA) Class III or higher at the Screening Visit;
• cardiomyopathy or significant cardiac conduction disorders;
• chronic liver disease;
• psoriasis (due to potential for increased risk for flare of skin disease);
• porphyria;
• and/or serologic evidence during Screening Visit of chronic infections including, but not limited to, human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV); ---Exception: hepatitis C antibody positive subjects are eligible with documentation of:
• receipt of HCV treatment AND
• a negative hepatitis C viral load test post-treatment.
• malignancy within the last 5 years, except for treated basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I; or
• alcohol or substance abuse within 1 year of treatment randomization.
• Prior or current systemic treatment with disease modifying anti-rheumatic agents, immunomodulatory agents, or glucocorticoids for IA, other rheumatic diseases, or other immunologic diseases;
• Tetracycline class antibiotic use for autoimmune conditions, taken within 12 months prior to Screening;
• Systemic corticosteroid use for non-IA conditions taken 28 days prior to Screening;
• More than 3 local corticosteroid injections, including but not limited to intra-articular, epidural, and intrabursal injections, during the 3 months prior to randomization;
• A history of a chronic condition that, in the opinion of the investigator, is highly likely to require therapy with systemic corticosteroids (oral or intravenous) within the study period, including but not limited to severe asthma and severe crystalline arthropathy;
• Women who are pregnant, breastfeeding or desire to become pregnant and/or breast feed within the duration of the 12-month treatment phase of the study;
• Women of childbearing potential who are not using or who do not agree to use adequate birth control measures (for example, total abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization, Depo-Provera, or hormonal implants) during the treatment phase of the study;
• An ideal or actual body weight ≤ 24.4 kg (e.g., ≤53 lbs) at Screening Visit;
• Any of the following laboratory abnormalities at the Screening Visit:
• Serum Creatinine Clearance < 50ml/min (as calculated by the Cockcroft-Gault formula: Creatinine clearance (CrCl)= (140-age) X (Weight in kg) X (0.85 if female) / (72 X Creatinine));
• Alanine Aminotransferase (ALT) > 2 times the upper limit of normal (ULN);
• Aspartate Aminotransferase (AST) > 2x the upper limit of normal (ULN);
• INR ≥ 1.25 if not currently taking anticoagulation therapy;
• Total white blood count (WBC) < 3.0 x 10^9/L;
• Platelet count ≤ 150 x10^9/L;
• Hemoglobin < 11.5g/dL;
• Absolute Neutrophil Count (ANC) < 2.0 x 10^9/L;
• Evidence of significant retinal disease upon eye examination during the screening period that in the opinion of the examiner would make identification of potential future retinal toxicity from HCQ difficult to evaluate: -- Retinal exam results may be applied to evaluations of subject eligibility for up to 6 months after the initial retinal exam.
• When, in the opinion of the study physician, the subject is not a good study candidate.

• Age greater than 18 years
• End Stage Renal Disease on Maintenance Hemodialysis
• Hypertension defined as systolic blood pressure > 140 mmHg pre-dialysis or >130 mmHg post dialysis
• Hemodialysis Vintage < 1 month
• Pregnancy
• Nadir Systolic Blood Pressure < 95 mmHg
• Pre or Post dialysis systolic blood pressure > 180 mmHg
• Decrease in systolic blood pressure >60 mmHg from pre to post dialysis
• Ultrafiltration rate >13 mL/kg/hr
• Peridialytic Midodrine Use
• Intradialytic Clonidine use
• Documented Antihypertensive Medication Non-adherence Bioimpedance will not be peformed on patients with
• amputated arms or legs
• cardiac defibrillator or pacemaker
• presence of metal prostheses

1. Women with chronic hypertension in pregnancy with new or untreated chronic hypertension, blood pressure 140-159 systolic or 90-104 diastolic OR known chronic hypertension on monotherapy and taking any antihypertensive and blood pressure ≤159/104 (including those with blood pressure <140/90); 2. Singleton; and 3. viable pregnancy <23 weeks of gestation. 1. Blood pressures prior to randomization ≥160 systolic or ≥105 diastolic (with or without treatment); 2. Patients currently treated with >1 antihypertensive medication (more likely to have severe chronic hypertension); 3. Multi-fetal pregnancy; 4. Known secondary cause of chronic hypertension; 5. High-risk co-morbidities for which treatment may be indicated:
• Class C or higher diabetes mellitus
• Chronic kidney disease
•including baseline proteinuria (>300mg/24-hr, p/c ratio >0.3, or persistent 1+ proteinuria*) or creatinine >1.2. *If a dipstick value at screening is more than trace, a clean catch or catheter urine should be obtained and re-tested by dipstick. If this shows trace or absence of protein, the patient is included. If it again shows 1+ protein, the patient is excluded until a 24-hr urine <300mg/24hr or p/c ratio is <0.3.
• Cardiac disorders: cardiomyopathy, angina, CAD
• Prior stroke
• Retinopathy
• Sickle cell disease; 6. Known major fetal anomaly; 7. Known fetal demise; 8. Suspected IUGR; 9. Membrane rupture or planned termination prior to randomization; 10. Plan to deliver outside the consortium centers (unless approved by the Clinical Coordinating Center) or unlikely to follow-up in the opinion of study staff or previous participation in this trial; 11. Contraindication to labetalol or nifedipine (e.g. know hypersensitivity); and (12) Current substance abuse or addiction (cocaine, methamphetamine) *The minimum age varies by center

• Males or females aged 18-75 years, inclusive.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Diagnosis of symptomatic WHO Group 1
• Has had a right heart catheterization (RHC) performed at or within 365 days of Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH
• Has WHO/ NYHA functional class II to IV symptoms.
• If on PAH-specific background therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or an agent acting on the nitric oxide (NO) pathway, a phosphodiesterase type 5 (PDE5) inhibitor or a soluble guanylate cyclase (sGC) stimulator. Subjects may be naïve to PAH-specific treatments.
• Stable is defined as no change in dose or regimen within 90 days of Screening and for the duration of the study.
• Subjects may be on 1 agent active in the NO pathway, i.e., either a PDE5 inhibitor or an sGC stimulator at stable dose (but not both).
• If the subject's disease-specific PAH therapy does not include a PDE5 inhibitor, the use of PDE5 inhibitor as needed for erectile dysfunction (ED) is permitted as long as the subject has not taken a dose within 48-hours of any Baseline or study related efficacy assessment. In addition, the subject must not take more than 8 sildenafil tablets, 6 vardenafil, or 4 tadalafil tablets per month for ED.
• Has a 6MWD of ≥50 meters on two consecutive tests, within 15% of each other, preferably performed on different days during Screening. If both tests are done on the same day, then they must be completed >4 hours apart.
• Both male and female subjects agree to use a medically acceptable method of contraception throughout the entire study period from informed consent through to the Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process (i.e., actively attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 30 days after the last dose of IMP. Medically acceptable methods of contraception include the following:
• oral, implantable, or injectable contraceptives (starting ≥60 days before dosing) and diaphragm with vaginal spermicide, cervical cap with vaginal spermicide, or male condom; male condom and partner using diaphragm with vaginal spermicide or cervical cap with vaginal spermicide;
• standard intrauterine device (IUD; e.g., Copper T 380A IUD), intrauterine system (IUS; e.g., LNg 20 IUS
•progesterone IUD), progesterone implant, or tubal sterilization (≥180 days after surgery);
• post vasectomy and male condom, partner using diaphragm with spermicide, cervical cap with spermicide, estrogen and progesterone oral contraceptives ("the pill"), estrogen and progesterone transdermal patch, vaginal ring, or progesterone injection. Women who are surgically sterile or postmenopausal for at least 12 months are not considered to be of childbearing potential. If of childbearing potential, female partners of male study participants should agree to utilize medically acceptable methods of contraception for the duration of study participation.
• Body weight <40 kg.
• Body mass index (BMI) ≥40 kg/m2.
• Group 2 to 5 pulmonary hypertension.
• PAH diagnosis ≥5 years at Screening.
• For subjects with HIV-associated PAH, any of the following:
• concomitant active opportunistic infections within 180 days of Screening.
• detectable viral load at Screening.
• cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Screening.
• changes in antiretroviral regimen within 90 days of Screening.
• Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction at Screening:
• BMI >30 kg/m2.
• Diabetes mellitus of any type.
• Systemic hypertension.
• Significant coronary artery disease, i.e., any of the following:
• Angina
• More than 50% stenosis in a coronary artery (by coronary angiography)
• Previous myocardial infarction
• Previous or planned coronary artery bypass grafting and/or coronary artery stenting
• Left atrial volume index (LAVi) >30 mL/m2.
• Diagnosis of Down syndrome. Subjects with Down syndrome are excluded due to the high potential of undiagnosed or poorly managed obstructive sleep apnea in this population.
• Malignancy within 5 years of Screening, with the exception of localized non-metastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix excised with curative intent.
• Recent history (i.e., within 1 year prior to Screening) of alcohol or drug abuse.
• Initiation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.

• Age ≥ 35 years
• Able to provide informed consent
• BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with metabolic syndrome
• Metabolic syndrome is defined as at least three of the following:3 1. waist circumference > 102 cm (40 in) in men and 88 cm (35 in) in women 2. triglycerides > 150 mg/dL or on treatment for hypertriglyceridemia 3. HDL cholesterol < 40 mg/dL in men and < 50 mg/dL in women 4. blood pressure > 130/85 mmHg or on treatment for hypertension 5. fasting glucose > 100 mg/dL
• Treatment with GLP-1 receptor agonists (including liraglutide, exenatide or others as they become available), DPP-4 inhibitors or insulin within the last 3 months.
• Receipt of any anti-obesity drug or supplement within 1 month prior to screening for this trial.
• Self-reported or clinically documented history of significant fluctuations (>5% change) in weight within 3 months prior to screening for this trial.
• History of diabetes mellitus (type 1 or 2) or on treatment with anti-diabetes medication.
• History of chronic pancreatitis or idiopathic acute pancreatitis (current or prior history).
• History of gallbladder disease (cholelithiasis or cholecystitis).
• Chronic kidney disease stage III or greater (eGFR<60 mL/min).
• Obesity induced by other endocrinologic disorders (e.g. Cushing Syndrome).
• Current or history of treatment with medications that may cause significant weight gain, within 1 month prior to screening for this trial, including systemic corticosteroids (except for a short course of treatment, i.e., 7- 10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g., imipramine, amitryptiline, mirtazapine, paroxetine, phenelzine, clorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium).
• Diet attempts using herbal supplements or over-the-counter medications within 1 month prior to screening for this trial.
• Current participation in an organized weight reduction program or within the last 1 month prior to screening for this trial.
• Participation in a clinical trial within the last 3 months prior to screening for this trial.
• Familial or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma.
• Personal history of non-familial medullary thyroid carcinoma.
• History of Major Depressive Disorder within the last 2 years.
• History of other severe psychiatric disorders, e.g., schizophrenia, bipolar disorder.
• Any lifetime history of a suicide attempt.
• A history of any suicidal behavior in the last month prior to randomization.
• Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the Investigator.
• Known or suspected hypersensitivity to trial product(s) or related product(s).
• Known or suspected abuse of alcohol or narcotics.
• Language barrier, mental incapacity, unwillingness or inability to understand.
• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. These include abstinence and the following methods: diaphragm with spermacide, condom with spermacide (by male partner), intrauterine device, sponge, spermacide, Norplant®, Depo-Provera® or oral contraceptives.

(answer must be yes to all to enter trial; check yes or no) º ≥ 18 years of age º Stage 1 Prehypertension (office BP 120-129/80-84 mmHg and normal ABPM <130/80) (answer must be no to all to enter trial) º Diabetes mellitus or other systemic disease º Cardiopulmonary disease º Treatment with antihypertensive medications º eGFR< 60 ml/min/1.73m2 º Pregnancy º Hypersensitivity to nitroprusside or phenylephrine º Psychiatric illness º H/o substance abuse or current smoker º H/o malignancy º Serum Phos <2.4 mg/dL or >4.5 mg/dL

1. Normotensive controls 2. Stage I (140-159/90-99 mmHg) untreated subjects with essential hypertension 3. Patients with PA and stage I (140-159/90-99 mmHg) hypertension 1. Congestive heart failure or coronary artery disease 2. Blood pressure averaging > 159/99 mmHg 3. Serum creatinine > 1.5 mg/dL 4. Diabetes mellitus or other systemic illness 5. Left ventricular hypertrophy by echocardiography or ECG 6. Pregnancy 7. Hypersensitivity to spironolactone, chlorthalidone, amlodipine, human recombinant insulin or Definity 8. Any history of substance abuse (other than tobacco) 9. History of gouty arthritis 10. Patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts 11. Hypersensitivity to perflutren, blood, blood products or albumin

9.1 Please indicate the inclusion criteria for enrollment: Six patients will participate in this study. Patients who present with uncontrolled hypertension (classified as clinic systolic blood pressure not at target level >140mmHg) to their primary care provider, emergency room (ER), specialist hypertension clinic or urgent care center will be asked to participate. Inclusion criteria include: 1. Patient presents with treated or untreated hypertension. 2. Adults aged 18-75 years, male or female 3. Patient has a clinic systolic blood pressure >140mmHg (average of 3 measurements), or >135mmHg in patients with type II diabetes 4. Patient has a daytime mean systolic blood pressure of ≥135 and diastolic blood pressure ≥85mHg based on 24 hours ambulatory blood pressure monitoring 5. Investigator judges that the subject can be managed safely for up to 12 weeks (4 weeks run-in plus 8 weeks post-treatment) with the use of standard background regimen of losartan/hydrochlorothiazide; patients with true resistant hypertension will be required to maintaining current antihypertensive regime for the duration of the study. Exclusion Criteria. Any patient who meets any of the following exclusion criteria will not be eligible for the study. 1. Patient has known or suspected secondary hypertension 2. Use of systemic drugs that may be used for the treatment of hypertension, for a non-hypertension indication for the trial, (e.g. atrial fibrillation/atrial flutter, heart failure, or calcium channel blocker for heart rate control). 3. Renal artery stenosis ≥ 50% diameter stenosis, or aneurysm(s) 4. Patients with atrial fibrillation. 5. Patient has type 1 diabetes 6. Patient has type 2 diabetes and evidence of peripheral neuropathy 7. History of previous stenting or balloon angioplasty of the renal arteries. 8. Untreated hypothyroid or hypo-parathyroid. 9. Orthostatic hypotension defined as >20 mmHg of systolic blood pressure and/or more than 10 mmHg in diastolic blood pressure fall after standing for 3mins 10. Renal artery anatomy as assessed by imaging (CT-angiogram or, MR angiogram or renal angiogram) meeting the following criteria: 1. Single renal artery or two renal arteries, if either has a diameter of < 5 mm or > 7 mm or a length of < 11 mm, 2. Accessory renal arteries with diameter > 2.0 mm and < 5.0 mm, 3. Excessive renal artery tortuosity based on Investigator judgment, 4. Moderate or severe, and diffuse renal artery calcification, and/or 5. Renal anatomic renovascular abnormalities (as assessed by renal imaging) that would increase the risk of renal catheterization. 11. Occlusive peripheral vascular disease that would preclude percutaneous access for the procedure. 12. Patient is known to have a unilateral non-functioning kidney or unequal renal size (> 2cm difference in renal length between kidneys). 13. Single kidney, kidney tumor, urinary tract obstruction, or other anatomic abnormality. Note: Simple renal cysts are not an exclusion. 14. Previous renal denervation. 15. History of renal transplantation. 16. Estimated eGFR (by the CKD-Epi formula) ≤45 mL/min per 1.73 m2, or on chronic renal replacement therapy. Patients with eGFR of <60 mL/min per 1.73 m2 will undergo additional renal function monitoring post procedure and/or contrast exsposure. 17. Unexplained hypokalemia (i.e. K < 3.5 mEq/L in patients not on a potassium-wasting diuretic). 18. Patient in whom an ABPM device cannot be used due to arm size (>50 cm arm circumference) or other reasons as identified by the Investigator or study coordinator. 19. Patient with severe cardiac valve stenosis for which, in the opinion of the Investigator, a significant reduction of blood pressure is contraindicated. 20. Heart failure greater than asymptomatic, New York Heart Association Functional Classification, class I, stage B heart failure 21. Patient with history of myocardial infarction, unstable angina pectoris, or stroke during the 6 months prior to screening 22. Known primary or secondary pulmonary hypertension. 23. Active infection. 24. Patient requiring chronic oxygen support or has severe COPD. 25. Patient has known hypersensitivity to contrast agents that cannot be adequately pre-medicated 26. A known hypersensitivity to Dehydrated Alcohol Injection. 27. Platelet count < 75,000/microliter and/or known bleeding diathesis or coagulopathy at time of screening. 28. Receiving anticoagulant drugs (e.g., warfarin, dabigatran, rivaroxaban, apixaban, edoxaban, or low molecular weight heparins), that in the opinion of the investigator, would affect the safety of the trial procedure. Use of antiplatelet drugs such as aspirin and/or thienopyridines (e.g., clopidogrel) are permitted. 29. Patient has current problems with substance abuse (e.g. alcohol, illegal drugs, etc.). 30. Patient on high dose of steroids or immunosuppressant therapy. 31. Patient has a history of myocardial infarction, unstable angina pectoris, or stroke during the 3 months prior to screening. 32. Patients with a history of pre-eclampsia 33. patients with fibromuscular dysplasia 34. patients with history of pyelonephritis within 6 months 35. patients with history of recurrent (> one episode) kidney stones or history of kidney stones within the last year 36. Pregnant or nursing or planning to become pregnant during the trial time period. Note: If subject is of childbearing potential, as defined in the protocol, agrees to use of contraception. 37. Any acute or chronic condition that the investigator believes will adversely affect the ability to interpret the data or will prevent the subject from completing the trial procedures, or has a life expectancy of < 12 months.

•Male or female, age greater than or equal to 45 years at the time of signing informed consent
•Body mass index (BMI) greater than or equal to 27 kg/m^2
•Have established cardiovascular (CV) disease as evidenced by at least one of the following: prior myocardial infarction; prior stroke (ischemic or haemorrhagic stroke); or symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) less than 0.85 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease Exclusion Criteria:
•Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
•HbA1c greater than or equal to 48 mmol/mol (6.5 %) as measured by the central laboratory at screening
•History of type 1 or type 2 diabetes (history of gestational diabetes is allowed)