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Small artery structure during antihypertensive therapy is an independent predictor of cardiovascular events in essential hypertension

Objective: Structural changes of small resistance arteries occur early in the disease process of essential hypertension and predict cardiovascular events in previously untreated patients. We investigated whether on-treatment small artery structure also identifies patients at elevated risk despite normalization of blood pressure (BP). Methods: We conducted a long-term follow-up survey of cardiovascular events in 134 moderate-risk patients with 9–12 months of well treated essential hypertension. All participants underwent subcutaneous biopsies with determination of small artery structure in terms of media to lumen ratio (M : L) before and during treatment. Results: After 9–12 months of treatment SBP was lowered from 164 ± 15 to 134 ± 14 mmHg (P < 0.01) and M : L reduced from 0.084 ± 0.028 to 0.075 ± 0.024 (P < 0.01). Mean follow-up hereafter was 15 years representing a total of 2035 years for the entire cohort. During this period 47 patients suffered a predefined cardiovascular event. For patients with on-treatment M : L above the mean value of the cohort (≥0.075), the hazard ratio was 2.14 [95% confidence interval (CI) 1.19–3.84, P = 0.01] and also those with M : L above mean +2SD of a normotensive population (≥0.098) had an elevated risk (hazard ratio 2.99, 95% CI 1.60–5.58, P < 0.01). Both results were adjusted for heart score (a 10-year mortality risk estimate integrating age, sex, smoking status, cholesterol level and SBP). Analysis of changes in M : L during treatment showed significantly higher event rates among patients with increased M : L and vice versa (hazard ratio 1.36 per 25% change, 95% CI 1.07–1.73, P = 0.013). Conclusion: On-treatment small artery structure identifies individuals still at increased cardiovascular risk despite long-term BP normalization and may be an additional target for therapy to prevent cardiovascular events.