New AIP study finds higher rates of hypertension, heart changes

Acute intermittent porphyria (AIP) is associated with a higher prevalence of high blood pressure (hypertension) and heart structural changes, according to a recent study.

The results suggest that age, body mass index (BMI) — a measure of body fat based on a weight-to-height ratio — and a history of nerve-related muscle weakness or paralysis were associated with higher odds of hypertension. Blood pressure also rose during AIP attacks, possibly due to sudden increases in stress-response hormones.

“Our study showed that systematic and multidisciplinary evaluation of patients with AIP had an impact on early diagnosis and proper management of hypertension in both phases of the disease,” the researchers wrote.

The study, “Hypertension and blood pressure profiles in patients with acute intermittent porphyria: a prospective case-control study,” was published in the European Journal of Internal Medicine.

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AIP can affect multiple organs

Porphyria refers to a group of genetic diseases caused by disruptions in the production of heme, a component of hemoglobin — the protein that carries oxygen in red blood cells. As a result, porphyrins and other heme precursors accumulate in various tissues and organs, which may lead to symptoms such as pain and gastrointestinal or urinary issues.

AIP, the most common form of acute porphyria, is characterized by sudden and commonly severe attacks that often affect multiple organs, including the nervous and cardiovascular systems, the kidneys, and the liver. However, the effects on the cardiovascular system are less studied, according to the researchers.

Here, a research team in Poland aimed to characterize blood pressure patterns among people with AIP. A total of 90 adults with overt AIP who had experienced at least one attack requiring hospitalization, along with 90 controls matched for age, sex, and BMI, were included in the Acute Intermittent Porphyria Related Abnormalities in Cardiovascular System (AIPRACUS) observational study (NCT05882136).

Participants had a mean age of 39 at study enrollment and about 30 at first AIP symptoms, and were mainly women (79%). They also had significantly higher levels of porphobilinogen (PBG) and 5-aminolevulinic acid (ALA), two precursors of porphyrins commonly used to diagnose the disease.

Patients had worse kidney function markers, including higher creatinine levels and urinary albumin-to-creatinine ratio, and lower estimated glomerular filtration rate. Fourteen patients had eGFR levels consistent with chronic kidney disease, and almost half (47%) experienced paresis or paralysis, which can cause muscle weakness or loss of movement.

A higher proportion of AIP patients than controls had hypertension (57.8% vs. 31.1%), and more than half of those cases in both groups were newly diagnosed during the study. Patients had higher 24-hour mean systolic blood pressure (123.7 vs. 116.9 mmHg), measured when the heart contracts, and diastolic pressure (77.7 vs. 73.2 mmHg), measured when the heart muscle relaxes.

Additionally, those with AIP more frequently had a non-dipping blood pressure pattern, when blood pressure does not drop by at least 10% during sleep (47.8% vs. 20%), and left ventricular hypertrophy, or enlargement of the left ventricle — the heart chamber that pumps oxygen-rich blood out to the body (18.9% vs. 7.8%).

Age, BMI, neurological history tied to hypertension

Further analysis identified three independent factors associated with hypertension: age, BMI, and a history of paresis or paralysis, which can cause muscle weakness or loss of movement. In particular, the odds of hypertension were about 2.5 times higher for each 10-year age increase, about 30% higher for each 1 kilogram per square meter (kg/m²) BMI increase, and about 13.2 times higher in patients with a history of paresis.

AIP attacks were mainly characterized by abdominal pain, and treatment usually included heme arginate, an intravenous heme therapy used to treat acute porphyria attacks.

During attacks, patients had significantly higher blood pressure and levels of metanephrine and normetanephrine – breakdown products of catecholamines, which are stress-response hormones – compared with periods of remission. A non-dipping pattern was also more frequent during AIP attacks (86% vs. 45%).

Changes in average blood pressure, both systolic and diastolic, were significantly associated with changes in normetanephrine levels. Associations with metanephrine levels were weaker, with a significant link seen for diastolic, but not systolic, blood pressure. During attacks, average diastolic blood pressure was also associated with urinary PBG and ALA levels. According to the researchers, this suggests that blood pressure “may be mediated by catecholaminergic surges.”

Overall, the study shows that “AIP is associated with a higher prevalence of hypertension, an unfavourable nocturnal [blood pressure] profile and cardiac structural changes,” underscoring “the need for cardiovascular monitoring in AIP patients.”