Hypertension with proteinuria ups risk of AF, cardiovascular events

Hypertension and proteinuria contribute to an increased risk of atrial fibrillation (AF) as well as stroke, heart failure admission, and cardiovascular death in older adults, and such risk is greater when both conditions are present, according to a study.

“Proteinuria could be a useful factor for predicting atrial fibrillation development and as a prognostic marker,” the researchers said.

The study sought to assess the effect of hypertension and/or proteinuria on the incidence of AF and determine the impact of temporal changes in proteinuria status on the incidence of AF. Overall, 85,434 participants with hypertension and 125,912 without hypertension (aged ≥60 years) from the Korea National Health Insurance Service-Senior cohort were analysed.

After inverse probability of treatment weighting, the adjusted incidences of AF were 0.51 per 100 person-years in participants without proteinuria and hypertension (controls), 0.69 in the hypertension only group, 0.78 in the proteinuria only group, and 0.99 in those with both hypertension and proteinuria. [J Hypertens 2022;40:128-135]

Compared with controls, the weighted AF risks increased by 37 percent (hazard ratio [HR], 1.37, 95 percent confidence interval [CI], 1.30–1.44; p=0.001) in the hypertension only group, 55 percent (HR, 1.55, 95 percent CI, 1.28–1.88; p<0.001) in the proteinuria only group, and 98 percent (HR, 1.98, 95 percent CI, 1.62–2.43; p<0.001) in the hypertension with proteinuria group.

Participants with proteinuria in the first examination had an increased AF risk even in the group in which proteinuria was resolved on the second examination (HR, 1.36, 95 percent CI, 1.12–2.31; p<0.001). The presence of proteinuria in the first and second analysis showed the greatest risk of incident AF (HR, 1.61, 95 percent CI, 1.12–2.31).

“Our study demonstrates that hypertension and/or proteinuria were related with AF development, especially if both are present,” the researchers said. “Proteinuria in hypertension may represent hypertensive end-organ damage and be related with an increased risk of AF development.”

Proteinuria could be an indicator of hypertensive end-organ damage, endothelial dysfunction, or cardiometabolic syndrome. Treating this condition might reduce the risk of AF or cardiovascular disease, according to the researchers. [BMC Neurol 2012;12:102; J Am Soc Nephrol 2006;17:2106-2211; Hypertens Res 2009;32:115-121]

Although several studies have shown that reducing proteinuria could lower the risk of cardiovascular event, there have been contradictory results on the effect of remitted proteinuria on such events. [J Am Soc Nephrol 2011;22:1353-1364; Diabetes Care 2018;41:163-170; Can J Cardiol 2019;35:77-91; Clin J Am Soc Nephrol 2016;11:1969-1977; Lancet Diabetes Endocrinol 2016;4:309-317]

“The progression of endothelial dysfunction and end-organ damage is a chronic process, so the risk of atrial fibrillation may be less affected by reducing proteinuria, especially in older patients like our report,” the researchers said. “In addition, longer periods of positive proteinuria may affect the risk of atrial fibrillation incidence even after proteinuria is resolved.”

Proteinuria normally develops in patients with diabetes mellitus and hypertension, both of which are risk factors for AF. In addition, proteinuria is independently associated with a higher risk of AF development. [Circulation 2011;123:1501-1508; Sci Rep 2017;7:6324; J Am Heart Assoc 2017;6:e005685; Diabetologia 2015;58:2259-2268]