August 11, 2022

Sodium content of soluble paracetamol linked to increased risk of CVD and mortality

Increased sodium intake from soluble paracetamol is associated with higher risk of CVD and mortality in patients with and without hypertension

Higher sodium intake resulting from the use of soluble paracetamol tablets has been found to increase the risk of cardiovascular disease (CVD) and mortality in patients regardless of their hypertensive status. This is the conclusion of a study conducted by researchers from the orthopedic department of Xiangya Hospital, in Changsha, China.

It has been known for some time that high sodium intake increases blood pressure and is therefore a risk factor for cardiovascular disease. Additionally, increased intake of this mineral has also been associated with an additional 1.65 million deaths from cardiovascular causes above a reference intake of 2.0 g per day. Additionally, studies suggest that, compared to moderate sodium intake, higher intakes are associated with an increased risk of cardiovascular events and death in hypertensive but non-normotensive patients.

Although reducing sodium intake is known to be associated with a reduced risk of stroke and fatal coronary heart disease in adults, it would be unethical to examine the impact of a increased intake on CVD risk and mortality, given the benefits of reduced intake. While dietary sodium is a major source of intake, sodium is also contained in several medications, including soluble paracetamol. For the current study, the Chinese team compared the risks of incident CVD and all-cause mortality associated with taking sodium-containing soluble paracetamol (acetaminophen) versus taking sodium-free formulations based on the patient’s hypertensive condition.

The team turned to the Health Improvement Network which is an electronic medical records database in the UK containing anonymised data for around 17 million patients as a source of information. They extracted data from two separate cohorts. The first included patients between the ages of 60 and 90 with a diagnosis of hypertension who were prescribed either a sodium or paracetamol-free formulation. The second cohort was similar although this time included patients without a diagnosis of hypertension. Sociodemographic data including gender, age, body mass index and various lifestyle factors were recorded and used as covariates in their analysis. The primary outcomes of interest were cardiovascular events, which included myocardial infarction, stroke and heart failure, and all-cause mortality.

Sodium intake and cardiovascular outcomes/mortality

For the first cohort, a total of 151,398 individuals with an average age of 78.3 years (65.8% women) and a history of hypertension were included, of whom 4,532 received paracetamol containing sodium. These were matched with a total of 147,299 without hypertension and an average age of 71.4 years (63.3% female), of whom 5,351 received a paracetamol formulation containing sodium.

Among those with hypertension, there were 122 cases of CVD among those who received the mineral and 3051 cases among the sodium-free group over a median follow-up period of 0.89 and 0.93 years respectively. This gave a 59% higher risk of incident CVD in people taking a paracetamol formulation containing sodium (Hazard ratio, HR = 1.59, 95% CI 1.32 – 1.92). In addition, the risk of all-cause mortality was more than doubled (HR = 2.05, 95% CI 1.92 – 2.19).

Among those who received a paracetamol formulation containing sodium but without hypertension, there was a 45% increased risk of CVD (HR = 1.45, 95% CI 1.18 – 1.79) and a risk of mortality increased by 87% (HR = 1.87, 95% CI 1.74 – 2.00).

Commenting on these findings, the authors noted that sodium-containing medications are an important but often overlooked source of the mineral. They concluded that individuals should avoid excessive unnecessary sodium intake while using sodium-containing paracetamol.

Zeng C et al. Acetaminophen containing sodium and cardiovascular outcomes in people with and without hypertension Eur Heart J 2022