Non-dipping heart rate & major adverse cardiovascular events in type 2 diabetes mellitus
Authors: Vassallo L , Xuereb R G , Fava S , Magri C 
Published: October 2022

Abstract

Background
Type 2 diabetes mellitus (T2DM) is a known major risk factor for cardiovascular disease. Whilst the influence of traditional risk factors such as hypertension, hyperlipidaemia and smoking are well-established determinants of major adverse cardiovascular events (MACE) in subjects with T2DM, the impact of insulin resistance, non-dipping blood pressure and heart rate status have not been adequately investigated.

Purpose
To determine predictors of MACE in a population of T2DM with underlying target-organ damage at baseline.

Methods
This study included 196 subjects with T2DM with advanced proliferative diabetic retinopathy. These subjects were recruited in 2008–2009 and were consequently followed up till February 2022 to determine independent predictors of MACE. At baseline, the median age of the participants was 64 years (IQR: 59–71 years) and the median diabetes duration was 18 years (IQR: 10–25 years). At baseline, all underwent 24-hour blood pressure and heart rate (HR) monitoring, and were assessed for markers of inflammation, insulin resistance, albuminuria, presence of peripheral neuropathy and peripheral vascular disease. Subjects whose night-time HR did not decrease by more than 10% as compared to daytime readings were classified as non-dippers. Similarly, a non-dipping BP profile was defined as a nocturnal decline of mean arterial pressure of less than 10%. At follow-up, the all-cause death rate was noted as well as MACE. The latter was defined as all-cause death, non-fatal MI, non-fatal stroke, coronary revascularisation or hospitalisation for unstable angina pectoris or heart failure. Univariate followed by multivariate Cox-regression analysis was performed to determine independent predictors of both all-cause mortality and MACE.

Results
At follow-up, 46% of the study participants had died whilst 63.1% had exhibited MACE. Multivariate analysis revealed age (OR: 1.05, 95% CI 1.02–1.07, p&lt;0.001), ESR (OR: 1.012, 95% CI: 1.001–1.02, p=0.035), GGT (OR: 1.005, 95% CI 1.001–1.009, p=0.025) and eGFR (OR: 0.99, 95% CI 0.98–0.99, p=0.016) at baseline to be independent determinants of all-cause death. With regards MACE, likewise, age (OR: 1.028, 95% CI 1.007–1.05, p=0.009), GGT (OR: 1.004, 95% CI 1.001–1.008, p=0.017) and eGFR (OR: 0.99, 95% CI 0.98–0.99, p=0.022) were shown to be independent determinants together with diabetes duration (OR: 1.034, 95% CI 1.014–1.055, p=0.001) and presence of non-dipping heart rate at baseline. The latter was shown to be the strongest predictor of MACE (OR: 1.55, 95% CI 1.06–2.26, p=0.024).

Conclusion
Whereas increasing age and impaired renal function are known risk factors for cardiovascular disease, this long-term follow-up study has highlighted the relevance of non-dipping heart rate in type 2 diabetes mellitus. Previous studies had shown an association between non-dipping heart rate and target-organ damage in diabetic subjects. The impact on MACE merits further investigation.

Funding Acknowledgement
Type of funding sources: None.