Blood pressure measurements during treadmill exercise testing and the risk for the future development of atrial fibrillation.

Hypertension is a well-established risk factor for the onset and progression of atrial fibrillation (AF). Blood pressure (BP) measurements during routine exercise stress testing (EST) may identify subjects at increased risk for developing AF. We performed a retrospective analysis of treadmill EST carried out using the Bruce protocol in patients aged ≥40 years without a history of AF (n = 17,617; 42% women). BP was measured at rest, peak exercise, and 2-min recovery and analyzed for its association with the risk for developing AF. During a mean follow-up of 7 years, AF was documented in 4.5% of the patients. The incidence rate of AF per 1000 person-years increased with the rise in CHA2DS2VASc scores (3.26 for a Score=0 to 19.78 for scores ≥6). In a multivariate analysis, adjusting for risk score components and exercise capacity, systolic BP measurements taken at rest (≥130 vs. ≤110 mmHg), peak exercise (>170 vs. ≤150 mmHg), and recovery (>150 vs. ≤130 mmHg) were associated with an increased risk for AF: the hazard ratios (HRs) were 1.56 (95% CI, 1.30-1.87), 1.21 (1.01-1.45), and 1.33 (1.10-1.62), respectively. Similarly, diastolic BP measurements taken at rest (≥90 vs. <80 mmHg), peak exercise (≥100 vs. <90 mmHg), and recovery (>90 vs. ≤80 mmHg) were associated with an increased risk for AF: the HRs were 1.80 (1.36-2.38), 2.08 (1.28-3.37), and 1.56 (0.81-3.02), respectively. The association of exercise BP with AF was further observed when the BPs were analyzed as continuous variables and in subjects without a baseline diagnosis of hypertension. In conclusion, systolic and diastolic BP taken at the rest, peak exercise and recovery phases of EST may provide independent predictive information regarding future risk for developing AF.

A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels.

INTRODUCTION: PCSK9 inhibitors (PCSK9i) are often used in statin-intolerant patients, aiming to reduce low-density lipoprotein cholesterol (LDL-C). Along with the growing experience with their use, there is a lack of evidence regarding the safety, tolerability, and clinical utility of PCSK9i in patients with markedly elevated creatine phosphokinase (CPK) levels. METHODS: We screened a comprehensive HMO database for patients treated with PCSK9i (Jan 2016-Dec 2019), in whom elevated CPK levels (>1,000 U/L) were documented prior to the initiation of therapy. Treatment plans, adherence, and the levels of CPK and LDL-C were analyzed. RESULTS: Of the 1,600 patients initiating treatment with PCSK9i, 26 had prior CPK values >1,000 U/L [median (IQR): 3,687 (1,876-8,344) U/L]. All 26 patients were previously treated with statins, which presumably resulted in adverse effects (myalgia in 24, and rhabdomyolysis in 5 patients) therefore mandating their discontinuation. Concomitant secondary factors for CPK elevation were present in 11 patients, and included renal failure, rheumatoid disorders, hypothyroidism, intensive exercise, proteinuria and genetic muscular disease. Of the 26 patients treated with PCSK9i, alirocumab was administered to 12 patients, and evolocumab to 14. Following the initiation of treatment with either drug, 24 patients (92%) demonstrated a reduction in CPK of >50%, and in 12 (46%) CPK levels have returned to normal values. With regard to treatment goals, 17 patients (65%) have achieved an LDL-C level of <70 mg/dL, and 12 (46%) have reached a level of <55 mg/dL. No serious adverse reactions were documented, and only 2 patients discontinued the treatment (not due to muscle symptoms or CPK elevation). CONCLUSIONS: PCSK9i constitute a safe, tolerable, and effective treatment for hyperlipidemia in patients with markedly elevated CPK. While statin intolerance is a major cause for CPK elevation, concomitant etiologies for increased CPK values were rather common.