| Summary: | <p><b>Background</b></p>
Elevated blood pressure is one of the major preventable causes of premature morbidity and mortality worldwide. Although pharmacological BP lowering has been demonstrated to prevent major cardiovascular events in the general population, its effects on less common outcomes, such as atrial fibrillation, and in specific populations, including patients with atrial fibrillation, heart failure and multimorbidity, remain poorly understood.
<p><b>Aims</b></p>
<p>This thesis aimed to investigate the effects of blood pressure lowering on new-onset atrial fibrillation; to investigate the effects of blood pressure lowering on cardiovascular outcomes in patients with atrial fibrillation and cardiometabolic multimorbidity; and to investigate the effects of drugs with blood pressure lowering properties on blood pressure and clinical outcomes in patients with heart failure. </p>
<p><b>Methods</b></p>
<p>Four studies were conducted to address the aforementioned aims. Analyses for the first three studies relied on data from the Blood Pressure Lowering Treatment Trialists’ Collaboration, which included individual participant data for fifty blood pressure lowering randomised controlled trials. The last study involved a systematic review and aggregate data meta-analysis of randomised controlled trials of drugs with blood pressure lowering properties in heart failure.</p>
<p><b>Results</b></p>
<p>The first study demonstrated that, in a relatively low-risk population, pharmacological blood pressure lowering, irrespective of its intensity, did not reduce the risk of new-onset atrial fibrillation (hazard ratio 1.01, 95% confidence interval 0.95 to 1.07 per each 5-mmHg reduction in systolic blood pressure). The second study found that blood pressure lowering reduced the risk of major cardiovascular events similarly in individuals with and without atrial fibrillation (hazard ratio for major cardiovascular events 0.91 (95% confidence interval 0.83 to 1.00) and 0.91 (95% confidence interval 0.88 to 0.93), respectively, for each 5-mmHg reduction in systolic blood pressure). The third study demonstrated that blood pressure lowering reduced the risk of major cardiovascular events by about 10%, irrespective of the number or pattern of cardiometabolic diseases at baseline (hazard ratio 0.90 (95% confidence interval 0.88 to 0.92) per each 5-mmHg reduction in systolic blood pressure). The fourth study showed that treatment with drugs with blood pressure lowering properties resulted in a small (about 2 mmHg), but significant, decrease in systolic blood pressure in patients with heart failure, with no evidence that treatment effects depended on the degree of blood pressure lowering or on baseline blood pressure. </p>
<p><b>Conclusions</b></p>
<p>This thesis improved our understanding of the efficacy and safety of blood pressure lowering, thus providing the much-needed evidence to inform therapeutic guidelines and clinical practice worldwide. This will ultimately reduce the burden of morbidity and mortality attributable to hypertension and conserve scarce healthcare resources that are struggling to meet the needs of our ageing and multimorbid population. </p>
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