Blood Pressure Classification and Causes of Secondary Hypertension

How is blood pressure graded?

Blood pressure is the force of blood on the artery wall. It depends on how much blood the heart pumps and on how full and narrow the vessels are, so it rises when the circulation holds too much salt and water, when vessels are squeezed, or when the heart pumps harder. Because the heart pumps in beats, the pressure is written as two numbers: systolic (SBP) over diastolic (DBP). SBP is the peak pressure as the heart contracts, and DBP is the trough pressure as the heart relaxes.

Blood pressure is graded by these numbers. The grading also separates hypertension with no identifiable cause from hypertension secondary to a specific condition. The cutoff for high blood pressure differs depending on the consensus followed for the diagnosis, treatment and prevention of hypertension, and the categories have changed over the years, which is why sources quote different numbers. One of the most commonly used cutoffs in studies is >139/89 mmHg. The categories are:

The “and” and “or” carry the logic. Normal and elevated require both numbers to be in range, because both pressures have to be low for the reading to sit in the safe zone. The hypertensive stages need only one of the two numbers to cross the cutoff, because either pressure alone marks a raised load on the vessels. A raised systolic pressure alone is therefore enough for the diagnosis.

The numbers sort people by their pressure, but why does a high reading matter, and how many people have one?

Why does a high reading matter, and how common is it?

Sustained high pressure raises resistance and afterload, which strains the vessels and the heart. Hypertension is therefore a major risk factor for stroke, ischemic heart attack and heart failure.

It is also one of the most common conditions in the USA, affecting about 30% of adults over 18 years. Recent studies show that prevalence has increased in all age groups, and it rises further with age.

So many people have a high reading. Does each of them have a cause that can be named?

Primary or secondary: how often is a cause found?

Most people diagnosed with hypertension have primary (essential) hypertension, which means high blood pressure with no single identifiable cause. The remainder have secondary hypertension, caused by an identifiable renal or endocrine condition. About 5–15% of all hypertensive patients have secondary hypertension. The proportion is higher in resistant hypertension, and higher in younger or referred patients; referral selects for suspicion, and pressure that stays high despite medicines hints that something outside the usual pattern is driving it.

Age shapes the figures. In children about 50% of cases are secondary, and secondary hypertension is more common in young adults than in older age groups. This contrasts with the rise of prevalence with age: essential hypertension becomes more frequent as people get older, so in a young patient less of the pressure is likely to be explained by that background, and the younger the patient, the more likely a search for a cause will find one. Age by itself therefore raises suspicion of a secondary cause. Recent studies suggest that the overall prevalence of endocrine-associated secondary hypertension is about 10%.

Secondary hypertension is the minority, yet it matters out of proportion to how often it occurs. The reason is that it is often correctable: the cause is a specific organ or hormone that can be removed, blocked or treated. Medication treats the pressure, whereas treating the underlying renal or endocrine disease treats the source, so it can normalise blood pressure that medication alone only controls.

If the cause is worth finding, where can it sit?

What causes secondary hypertension?

Secondary hypertension has renal, drug-related, sleep-related and cardiovascular causes besides hormonal ones. All of them push the same three levers of pressure. The main causes are:

• primary renal diseases
• oral contraceptive use
• sleep apnea syndrome
• congenital or acquired cardiovascular diseases
• hormonal excess

Endocrine hypertension is hypertension driven by hormonal excess. Hormones are natural suspects because they control exactly these levers, and endocrine causes raise blood pressure through different mechanisms: sodium retention expands the volume, vasoconstriction narrows the vessels, and increased cardiac output raises the flow. Because the hormones act differently, each endocrine cause carries its own clinical clues and its own treatment.

Which hormonal excesses are on the list?

Which hormonal excesses raise blood pressure?

The most common endocrine cause is primary hyperaldosteronism, which is excess aldosterone production by the adrenal gland. The other endocrine causes are:

• hypercortisolism (excess cortisol)
• pheochromocytoma (a catecholamine-secreting tumour)
• acromegaly (excess growth hormone)
• hypothyroidism and hyperthyroidism (too little or too much thyroid hormone)

Grouped by the gland that produces the excess hormone, the endocrine causes are:

• Adrenal-dependent: pheochromocytoma and sympathetic paraganglioma; primary aldosteronism; hyperdeoxycorticosteronism, including congenital adrenal hyperplasia, 11β-hydroxylase deficiency, 17α-hydroxylase deficiency and deoxycorticosterone-producing tumor; Chrousos syndrome; Cushing syndrome; apparent mineralocorticoid excess
• Parathyroid-dependent: hyperparathyroidism
• Pituitary-dependent: acromegaly; Cushing disease
• Thyroid-dependent: hypothyroidism; hyperthyroidism
• Other endocrine causes: secondary hyperaldosteronism; vitamin D deficiency

The same pressure rise can also come from outside the endocrine system, so what are the other causes?

Which causes lie outside the endocrine system?

The other causes are grouped by the system involved.

• Renal causes (2.5–6%): polycystic kidney disease; chronic kidney disease; urinary tract obstruction; renin-producing tumor; Liddle syndrome. The kidney regulates salt, water and renin, so disease of the kidney, or reduced flow to it, can retain salt or activate the RAAS.
• Renovascular causes: renal artery stenosis; fibromuscular dysplasia; atherosclerosis. When the renal artery narrows, less blood reaches the kidney, and the kidney responds as if volume were low by activating the RAAS.
• Vascular causes: coarctation of aorta; vasculitis; collagen vascular disease.
• Neurogenic causes: brain tumor; autonomic dysfunction; sleep apnea; intracranial hypertension.
• Drugs and toxins: alcohol; cocaine; cyclosporine, tacrolimus; NSAIDs; erythropoietin; adrenergic medications; decongestants containing ephedrine; herbal remedies containing licorice or ephedrine; nicotine.

With so many possible causes, a clinician cannot assume the cause is hormonal. Whom should a clinician suspect, and how are the hormonal causes tested for?