Apparent treatment-resistant hypertension associated lifetime cardiovascular risk in a longitudinal national registry

Abstract

<p><strong>Aims: </strong>Apparent treatment-resistant hypertension (aRH), wherein blood pressure elevation requires treatment with multiple medications, is associated with adverse cardiovascular events over the short-term. We sought to evaluate the degree of excess risk associated with aRH across the lifespan. <br></p><p><strong>Methods and results:</strong> We identified all individuals with hypertension who were prescribed at least one anti-hypertensive medication from the FinnGen Study, a cohort of randomly selected individuals across Finland. We then identified the maximum number of concurrently prescribed anti-hypertensive medication classes prior to age 55 and classified those co-prescribed ≥ 4 anti-hypertensive medication classes as aRH. Using multivariable adjusted Cox proportional hazards models, we assessed the association of aRH well as the number of co-prescribed anti-hypertensive classes with cardiorenal outcomes across the lifespan. Among 48 721 hypertensive individuals, 5715 (11.7%) met the aRH criteria. Compared to those prescribed only one anti-hypertensive medication class, the lifetime risk of renal failure increased with the addition of each additional medication class, beginning with the second, while the risk of heart failure and ischaemic stroke increased after addition of the third drug class. Similarly, those with aRH suffered increased risk of renal failure (hazard ratio 2.30, 95% CI 2.00-2.65), intracranial haemorrhage (1.50, 1.08-2.05), heart failure (1.40, 1.24-1.63) cardiac death (1.79, 1.45-2.21), and all-cause death (1.76, 1.52-2.04). <br></p><p><strong>Conclusion:</strong> Among individuals with hypertension, aRH that develops prior to mid-life is associated with substantially elevated cardiorenal disease risk across the lifespan.<br></p><p><strong>Lay Summary:</strong> Examination of medical records from over 48 000 Finnish individuals found that the risk of future adverse medical events increased with a need for greater number of blood pressure medications in middle age.Using the number of blood pressure medications simultaneously prescribed before age 55, the risk of kidney problems increased with the addition of each antihypertensive medication, starting after the first, while the risk of heart failure and stroke increased with the addition of two more blood pressure medications.Individuals with very difficult to treat high blood pressure (needing at least four medications) had greater risk of nearly all assessed clinical outcomes, including death. These findings indicate that needing more medications to treat blood pressure in mid-life is associated with worse clinical outcomes. The most important goal for such patients should be to improve their blood pressure control early in life.<br></p>