In 2017, Jeffrey C et al won the Nobel Prize in Physiology or Medicine for discovering the molecular mechanism of the biological clock, ushering in a new era of biorhythm research. Circadian Rhythm is an important biological mechanism involved in almost all diseases, including cancer, infections, and neurological disorder [9-11]. Circadian rhythm has been extensively studied in physiology, pathology, and disease of the cardiovascular system through its effects on heart rate, blood pressure, and vascular endothelial function [3, 12-14]. Normal BP has a circadian rhythm of 10% to 20% drop at night which is called a dipper pattern. AR-BP can lead to arteriosclerosis, left ventricular hypertrophy, retinopathy, kidney damage, and so on [3, 15-17].
A study of 718 participants in North China found that RD-SBP was a risk factor for CAD , while another clinical study conducted in South China put that it was not RD-SBP but RD-DBP that increased the risk of CAD . The above studies didn’t focus on diabetic patients and the diagnosis of CAD was just based on clinical symptoms or history rather than the gold standard of coronary imaging. A study in the US of 68 male CAD patients who underwent CAG regarded both SBP and DBP drop less than 10% at night as non-dipper, and found that non-dipper BP was a risk factor for CAD .
The study of BP rhythm in diabetic patients is not rare. Kristina et al pointed out that there was an interaction between AR-BP and diabetes, compared to the dipper pattern, diabetes was more common in non-dipper, and there was also a greater non-dipper pattern in diabetic patients , it was also shown in our study. This mutually reinforcing association might increase the risk of CAD . The previous study also tried to confirm the nocturnal BP increase in diabetic patients with CAD, but due to the small sample size(n=36), no statistically significant was seen . Our study further confirmed this relationship with a large population and also found out there was a larger probability of CAD in diabetic patients who own a nocturnal increased BP or less decline DBP. We should pay more attention to this group of people and handle timely in consideration of CAD, in the meanwhile, further examination of the coronary artery is worthy.
In the study of risk factors for CAD, as in general public, male, smoking, alcohol abuse, level, and duration of hypertension were still risk factors for CAD in diabetic patients. Interestingly, there was a higher risk of CAD in a diabetic patient with lower BMI but had a longer diabetes course and a higher HbA1c. Lower BMI didn’t mean a lower risk for CAD in diabetic patients due to it referred to uncontrolled blood glucose and represented a hypermetabolic state in the body. So, well blood glucose management is essential to reduce CAD. As for BP, higher SBP-24 and SBP-B were associated with a higher risk of CAD, while AR-SBP and AR-DBP were risk factors for CAD. Further analysis showed that RD-SBP, RD-DBP, and ND-DBP contributed. This connection was still significant after adjusting for the gender, age, HbA1c, etc, as Model 1 and Model 2 put. In a word, there is a higher risk factor for CAD in diabetic people with RD-SBP, RD-DBP, or ND-DBP patterns.
Many scholars tried to explore the mechanism between diabetes and abnormal BP rhythm. Italian researcher V Spallone suggested that the nocturnal BP dropped less in people with diabetes due to autonomic neuropathy, and in type 2 diabetic people, autonomic neuropathy was the only reason for fewer nocturnal BP decline . Kazuomi et al also found that the BP rhythm was related to autonomic nervous activity by studying the antihypertensive effect of α1-receptor blocker on different types of BP rhythm subjects . Non-dipper BP was associated with increased sympathetic nervous activity and decreased parasympathetic nervous activity, which increased mortality in subjects .
However, some scholars doubt the role of autonomic neuropathy in the abnormal rhythm of BP in diabetic patients. Spanish researcher Jose Cabezas-Cerrato found no significant difference in non-dipper BP patterns between patients with and without autonomic neuropathy in a study of 101 diabetic patients . Yu-Sok Kim proposed that the non-dipper BP pattern in diabetic patients was associated with microangiopathy but not autonomic neuropathy . We knew that there were higher levels of inflammatory markers, high platelet activity, and hypercoagulable state in patients with diabetes , and there were significant differences in vWF, fibrinogen, and sP-Selectin levels between non-dipper and dipper BP patients showed that the hemostatic mechanism was active and endothelial function was damaged in non-dipper BP pattern patients . On the other hand, the platelet activity was increased and the inflammatory reaction was heavy in non-dipper patients . The above suggests that diabetic patients and non-dipper BP pattern patients may have common pathology leading to an increased risk of CAD.
This common mechanism may be organized by genes. Marcin Wirtwin et al constructed a Genetic Risk Score to demonstrate that nocturnal SBP rising was depended on genes and was associated with major adverse coronary events in patients with CAD . Further analysis found that polymorphisms of genes related to CAD (MIA3、MEAS、PCSK9、SMG6、ZC3HC1) were associated with AR-SBP and AR-DBP . MEAS, PCSK9, and SMG6 [17, 27, 28] also played important roles in the development of diabetes. From this, we can infer that the high risk of CAD in diabetic patients with AR-BP may be genetically determined.
This is the first study to explore the relationship between BP rhythm and CAD which definite diagnosis by CAG or CCTA in diabetic patients in Southwest China. Considering the effects of acute cerebral infarction, sleep apnea, and shift work on BP rhythm, we did not include the patients above. Patients who had undergone CAG, coronary stent implantation, coronary bypass grafting in past, or suffer acute myocardial infarction this time were also excluded due to we could conclude CAD easily without a doubt. The purpose of this study is to provide a basis for CAD in diabetic patients who may suffer neuropathy and do not have a typical clinical presentation of angina. Our study still has some limitations like did not include antihypertensive and antidiabetic drugs. In previous studies of CAD, only antiplatelet drugs showed significant differences between dipper and non-dipper BP patterns at baseline, while statins and all kinds of antihypertensive drugs had no difference in patients. Other studies suggested that the timing of medication-taking makes sense, while most Chinese patients take antihypertensive drugs in the morning. For antidiabetic agents, a meta-analysis showed that sodium-dependent glucose transporters 2 inhibitors (SGLT2i) reduced 24-hour BP in patients with diabetes and hypertension , and when changed from dipeptidyl peptidase-4 inhibitor to SGLT2i, the AR-BP significantly reduced . Whether SGLT2i can reduce AR-BP and thus reduce the incidence of CAD in diabetic patients is the task we will undergo in the future. In addition, we speculate that the relationship between BP rhythm, diabetes, and CAD is organized by genes, multi-center and multi-ethnic research is necessary.