Chapter 3: Secondary hypertension

Secondary forms account for only a small proportion of all hypertension, most of which is primary hypertension. Their true prevalence is not known precisely because published data are affected by selection bias, undiagnosed cases and inconsistent definitions. Some experts also question whether obstructive sleep apnoea (OSA), a phenotype frequently seen in people with severe obesity, should always be classified as a secondary form.

Despite their limited prevalence, detecting and treating secondary hypertension is important. These forms often carry high or very high morbidity and mortality risk, and the blood pressure may improve substantially when the underlying cause is treated in time. They require targeted diagnostic strategies to identify the cause and select effective medication or an appropriate intervention.

Secondary hypertension is a frequent explanation for severe or truly resistant hypertension, deterioration of previously controlled pressure, or HMOD that appears disproportionate to the duration or severity of hypertension. It is particularly relevant in younger people under 40 years, although some causes—such as atherosclerotic renal-artery disease—are more common at older ages.

Patient features that should raise suspicion of secondary hypertension

• Age under 40 years with grade 2 or grade 3 hypertension, or hypertension of any grade in childhood.
• Sudden onset after previously documented normal blood pressure.
• Acute deterioration in a person whose hypertension had previously been well controlled.
• True resistant hypertension.
• Hypertensive urgency.
• Severe grade 3 or malignant hypertension.
• Severe or extensive HMOD, particularly when disproportionate to the duration and severity of the blood-pressure elevation.
• Clinical or biochemical findings suggesting an endocrine cause.
• Clinical features suggesting atherosclerotic renovascular disease or fibromuscular dysplasia causing renal-artery stenosis.
• Clinical features suggesting obstructive sleep apnoea.
• Severe hypertension in pregnancy, above 160/110 mmHg, or acute worsening in a pregnant woman with pre-existing hypertension.

Screening every person with hypertension for secondary causes is neither practical nor cost-effective. In many cases, however, the clinical presentation provides clues to the presence and likely nature of a secondary cause.

The commonest causes are primary aldosteronism, kidney disease and renovascular disease. Cushing syndrome, pheochromocytoma, paraganglioma and coarctation of the aorta are less common. The different causes have different age distributions. When clinical suspicion is present, prompt referral to a specialist hypertension centre is appropriate so that targeted testing and subsequent treatment can be arranged.

Genetic causes of secondary hypertension

Several rare monogenic forms have been described. Mutations in specific genes—most of which encode proteins involved in tubular sodium reabsorption or steroid metabolism—are responsible for the hypertension.

One exception is autosomal-dominant hypertension with brachydactyly, in which the mechanism lies within vascular smooth-muscle cells. Hypertension is usually already present in childhood or early adulthood, although age at onset and severity can vary with lifestyle, environmental factors and genetic susceptibility.

Specific medicines can correct some molecular defects, for example amiloride in Liddle syndrome and dexamethasone in glucocorticoid-remediable aldosteronism.

Routine genetic testing for pheochromocytoma and paraganglioma (PPGL) should be performed through accredited genetic laboratories. A germline mutation is found in approximately 40% of cases, and some genetic syndromes carry a high risk of malignancy and require careful long-term follow-up.