The Role of the Immune and Inflammatory Systems in Hypertension

A Study of the Roles of the Immune and Inflammatory Systems in Hypertension

To define the cytokine and cellular immune signature of primary hypertension. Cross sectional clinical/laboratory study.

Experimental data show the presence of immune and inflammatory systems dysregulation in hypertension. Understanding of the inflammatory and immune nature of hypertension is currently based on studies in rodent models of hypertension, but is supported by human epidemiological and genome wide association studies (GWAS) studies. It is now essential to identify key checkpoints and inflammatory mechanism(s) involved in human hypertension in comprehensive and sufficiently powered studies, which will then be able to guide subsequent in-depth hypothesis-driven mechanistic studies. This approach may provide the basis for future randomized clinical trials (RCTs).

To define the relationships and predictive value of the immune signature of hypertension and clinical phenotypes of hypertension :

• Predictive value of immune signature for blood pressure parameters measured by ambulatory blood pressure measurements (ABPM)
• Predictive value of immune signature for endothelial function assessed by Endo-PAT2000 and flow mediated dilatation (FMD) both complementary non-invasive techniques.
• Predictive value of immune signature for vascular stiffness and central pressure assessed by SphygmoCor
• Predictive value of immune signature for renal function parameters
• Predictive value of immune signature for cognitive function. To define genetic determinants of immune signature of hypertension.

Inclusion Criteria:

• Age between 18-55 years
• Cases: Office blood pressure ≥140 and ≥90
• Controls: Office blood pressure <140 and <90 and age, sex and BMI matching to cases

Exclusion Criteria:

• Age >55 years old;
• Secondary hypertension (including e.g. adrenal tumours, pheochromocytoma, renal artery stenosis; thyroid disease)
• Acute inflammatory disorders incl. flu, rhinitis, sinusitis etc. within 3 weeks;
• hospitalization within the past 3 months;
• Life expectancy of < 3 years;
• History of alcohol/substance abuse
• Inflammatory conditions e.g. Allergic disorders; chronic infections, COPD, tuberculosis; hepatitis B or C; pneumonitis, bronchiectasis; pericardial or pleural effusion, ascites; liver disease;
• Chronic inflammatory/autoimmune conditions such (e.g. SLE, rheumatoid arthritis, ulcerative colitis/Crohn's disease; non-basal cell malignancy or myelo- or lymphoproliferative disease within the past 5 years; known HIV+; Immunizations (3 months); pulmonary hypertension;
• Pregnancy, nursing;
• History of symptomatic coronary artery disease (events) or heart failure;
• BMI>40,
• diabetes/glucose intolerance (fasting glucose, HbA1; testing, glucose challenge where indicated);
• Known albuminuria/microalbuminuria;
• GFR<60mL/min/1.73m2.
• Any chronic concurrent treatment: Use of systemic or local steroids/immunosuppressive agents (within 6 months) of the inclusion; Current (within past 3 months) use of anti-hypertensive medication;
• Major depressive illness or other psychiatric conditions.
• Participants who decline participation in the study or who are unable to provide informed consent