Genetic and Secondary Causes of Blood Pressure Variation

distribution of bp in US and Canada- age related increase in bp

consequences of uncontrolled hypertension

suboptimal blood pressure control among US adults with hypertension

hypertension as a multifactorial disease

environmental causes of hypertension

-NSAIDs

-sympathomimetic agents (weight loss pills, decongestants, cocaine)

-amphetamine and amphetamine-like substances

-exogenous glucocorticoids and mineralocorticoids

-antidepressants

-alcohol

-oral contraceptive pills and exogenous estrogen

-immunosuppressants

-erythropoietin

-natural licorice

-herbal agents ephedra or ma huang

environmental causes of hypertension- obesity

glucocorticoid remediable aldosteronism

normal v. AME for lumen to blood

normal v. AME with licorice ingestion for lumen to blood

-adrenal hyperplasia

primary aldosteronism

-very common in patients with moderate to severe hypertension

-accounts for 10-20% of resistant hypertension

-40% of cases produced by aldosterone-producing adenoma (usually benign and unilateral)- curable by surgical removal of affected adrenal gland

-60% cases caused by bilateral hyperplasia- responsive to mineralocorticoid antagonists

K-channel mutation in aldosterone producing adenomas

-”string of beads” characteristic of medial fibromuscular dysplasia

-renal artery stenosis

renovascular hypertension

-diagnosis: renin levels can be high but normal levels do not rule out renal artery stenosis

-imaging studies: sonography with duplex doppler, magnetic resonance angiography, CT angiography, angiography

-due to fibromuscular dysplasia in young individuals- treat with angioplasty

-due to atherosclerotic disease in older individuals with CV risk factors: suspect with pre-existing peripheral vascular disease or long history of smoking, recurrent flash pulmonary edema, treatment with angioplasty + stent placement

pathogenesis of many acquired or genetic forms of secondary hypertension

-pheochromocytoma

germline mutations associated with pheochromocytoma and paraganglioma

tubules with thiazide and loop diuretics

hypotensive disorders with hypokalemic metabolic alkalosis- Gitelman syndrome, Bartter syndrome

___ is a common cause of hypertension

-chronic kidney disease

monogenic kidney disease with specific therapies- syndrome, gene(s), therapy

summary