Reverse-dipping BP, Heart Rate Variability Linked to Increased All-cause Mortality in Diabetes

Non-dipping and reverse dipping blood pressure patterns in patients with diabetes are associated with an increase in the prevalence of cardiac autonomic neuropathy and decreased probability of survival, according to a unique study presented at the American Heart Association’s (AHA) Hypertension Scientific Sessions being held virtually September 27 to 29, 2021.

Study authors note that while abnormal patterns of circadian BP and reduced heart rate variability (HRV) are recognized risk factors for cardiovascular (CV) events in persons with diabetes, most studies looking at all-cause mortality associated with the disturbances in this population have been limited to 10 years of follow-up.

“Previous studies have shown that non-dipping is linked to kidney and cardiovascular disease in healthy individuals and in people with hypertension, or type 1 or type 2 diabetes,” said lead author Martina Chiriacò, MD, an investigator in the department of clinical and experimental medicine at the University of Pisa in Italy, in an AHA statement. “However, the long-term effects of non-dipping on death among people with diabetes remains unclear, and information on reverse dippers is extremely scarce. We sought to investigate these two aspects to highlight whether altered patterns of blood pressure might predict mortality risk in people with type 1 or type 2 diabetes.” She also noted there is little long-term data on the association between HRV and mortality in the diabetes population.

Chiriacò and colleagues studied a group of 349 patients with type 1 or type 2 diabetes recruited in Pisa, Italy in 1999 for 21 years. All had 24-hour ambulatory BP and HRV monitoring data available. The cohort’s average age was 57 years and 52% were women. Mean BMI was 29.4 kg/m², mean A1C, 8.6% and 284 participants had type 2 diabetes. Hypertension was identified in 82% and uncontrolled hypertension in 73%, the latter despite being treated with antihypertensive medication.

For purposes of the study, investigators defined dipping status as a ≥10% decline, non-dipping status as a <10% decline, and reverse dipping status as a ≥0.1% increase in average night-time systolic BP (SBP) vs average daytime SBP. Based on these criteria, 166 participants were considered dippers, 144 were considered non-dippers, and 39 were considered reverse dippers.

Chiriacò et al report that during a median follow-up period of 21 (range 14-21) years—a total of 6251 person-years—there were 136 deaths (39%). Compared with nocturnal dippers, prevalence of cardiac autonomic neuropathy was progressively higher in in non-dippers and reverse dippers (11%, 16% and 31%, respectively). When compared further with overnight dippers (D), non-dippers (ND) and reverse dippers (RD) also exhibited, respectively:

• Low HRV: D 45% vs ND 53% vs RD 62%
• 24-hour hypertension:  D 40% ND 60% RD 67%
• Isolated nocturnal hypertension:  D 5% ND 27% RD 49%)
• Postural hypotension: D 14% ND 26% RD 43%
• Lower prevalence of white-coat hypertension: D 31% ND 17% RD 13%

Authors also found a pattern of progressively lower mean overall survival (OS) in reverse dippers (16.1±5.3 years) and non-dippers (17.5±5.3 years) compared with nocturnal dippers (18.6±4.6 years).

Investigators noted reverse dippers appeared to be at more than 2 times the risk of all-cause mortality (HR, 2.3 [95% CI, 1.4-3.8]) compared to dippers after adjustment for age, sex, BMI, office SBP, plasma glucose, and diabetes duration and type. Mean OS, they found, was reduced in patients with low HRV compared to high HRV (16.9±5.5 and 18.8±4.4 years, respectively), but the adjusted risk was similar between the groups (HR, 1.3 [95% CI, 0.9-1.9]). There were no significant interactions seen between BP, HRV, and diabetes type and OS.

“Our study shows that 1 in 10 people with type 1 or type 2 diabetes could be a reverse dipper, and that this condition likely more than doubles the risk of death from any cause over 21 years’ time, regardless of blood pressure control,” said Chiriacò in the AHA statement. “It is important that health care professionals look for abnormal blood pressure dipping patterns in people with type 1 or type 2 diabetes. There are strategies to reduce blood pressure during the night.”

She noted that ambulatory BP monitoring is an inexpensive, widely available screening and monitoring tool for the diagnosis of abnormal BP and heart rate circadian variations. “We support using this screening to optimize treatment for people with diabetes,” said Chiriacò.

The study abstract was published simultaneously in the journal Hypertension.

Source: Martina Chiriacò M, Sacchetta L, Forotti G, et al. Prognostic value of 24-hour ambulatory blood pressure and hear rate patterns in diabetes: a 20-year longitudinal analysis of the chronic diabetes complications and all-cause mortality in Pisa from 1999 onwards (CHAMP1ON) study cohort. Hypertension. 2021;78:AT1. Originally published 27 Aug 2021 https://doi.org/10.1161/hyp.78.suppl_1.T1