Effects of systolic and diastolic blood pressure rhythm on coronary artery disease in type 2 diabetic patients: a retrospective cross-sectional study

doi:10.21203/rs.3.rs-1546377/v1

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Effects of systolic and diastolic blood pressure rhythm on coronary artery disease in type 2 diabetic patients: a retrospective cross-sectional study

https://doi.org/10.21203/rs.3.rs-1546377/v1

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Background: Studies put it there was an interaction between diabetes and abnormal blood pressure rhythm, and they both increased the morbidity and mortality of coronary artery disease (CAD). We aimed at analyzing the effects of abnormal rhythm (AR) of blood pressure (BP) and each kind of systolic or diastolic blood pressure (SBP, DBP) pattern on CAD in patients with type 2 diabetes in Southwest China.

Methods: A retrospective cross-sectional study involved 853 type 2 diabetic patients with 24-hour ambulatory blood pressure monitoring divided into CAD and non-CAD groups through imaging examination of the coronary artery. SBP and DBP were divided into dipper (D), non-dipper (ND), reverse dipper (RD), and extreme dipper (ED) by nocturnal BP decline rate, respectively. The difference in mean 24-hour, daytime, bedtime SBP and DBP, and BP rhythm between groups was compared by variance analysis. The association between different BP rhythms and CAD was analyzed by multivariate logistic regression when adjust for clinical, laboratory, and BP parameters.

Results: Most diabetic patients had non-dipper BP patterns in both CAD and non-CAD groups, while the CAD group had a higher percentage of RD in both SBP and DBP than non-CAD. More CAD occurred in RD-SBP than D-SBP (P<0.001), RD-SBP than ND-SBP (P<0.001), RD-DBP than D-DBP (P<0.001), and ND-DBP than D-DBP (p=0.006). AR-SBP (OR=1.622, P=0.015), AR-DBP (OR=1.774, P=0.001), RD-SBP (OR=2.320, P<0.001), RD-DBP (OR=2.140, P<0.001), ND-DBP (OR=1.648, P=0.006) were risk factors for CAD and those relationships were still significant after adjust for different parameters.

Conclusion: Abnormal BP rhythm, especially reverse dipper pattern was a risk factor for CAD regardless of SBP or DBP in diabetic patients. While for non-dipper, only the non-dipper DBP pattern had a risky influence.

Ambulatory blood pressure monitoring

Circadian blood pressure

Circadian rhythm

Non-dipper

Reverse dipper

Type 2 diabetes

Coronary artery disease

As 《World Health Statistics 2019》reported, ischemia heart disease was still the premier cause of death, and diabetes was the ninth death reason, from 2000 to 2019, people died of diabetes rising 70% around the world. Diabetes has become a world public health problem and as an admitted risk factor of coronary artery disease (CAD), it led to the incidence and mortality of CAD rising.

Blood pressure (BP) has been shown to be associated with CAD, but there are limitations on office BP such as numbered BP readings, possible “White Coat Hypertension” effects, and no assessment for changes in BP over time. 24-hour ambulatory blood pressure monitoring (24h-ABPM) is more advantageous in comprehensively assessing BP than office readings, and it has advantages in assessing target organ damage including CAD, mainly by measuring BP variability [1], BP morning peak [2], BP rhythm [2-4] and other aspects. The abnormal rhythm of BP (AR-BP) leads to arteriosclerosis and increases the mobility and mortality of CAD [3-6].

Normal BP falls 10%-20% at night which is called dipper blood pressure [2]. Diabetic patients have less nocturnal BP decline and have AR-BP due to autonomic neuropathy [7]. For the same reason, people with diabetes might not have typical angina symptoms, so it is difficult to identify and intervene CAD in time in diabetic people.

Previous studies in the Iranian population showed that non-dipper and reverse dipper systolic BP patterns were risk factors for CAD in diabetic patients [2], but diastolic BP rhythm was not referred, and CAD diagnosis was just based on medical history. This study aims to investigate the role of different systolic and diastolic blood pressure (SBP, DBP) rhythms in Southwest Chinese diabetic patients who are clinically suspected of CAD. Therefore, primary prevention can be taken earlier to reduce the morbidity of CAD, and secondary prevention can be taken promptly to reduce the mortality of CAD in diabetic patients.

Study population

Eight hundred and fifty-three type 2 diabetic patients (discharge diagnosis was E11.900 in GB/T14396-2016 Classification and codes of diseases) were hospitalized in the Department of Cardiology or Geriatrics of Second Affiliated Hospital, Chongqing Medical University, Chongqing, China from January 1, 2019, to August 31, 2021, and met the followed criteria were selected. Their clinical records were extracted. Inclusion criteria:(1) suspicious diagnosis of CAD in the hospital course, (2) coronary computed tomography angiography (CCTA) or coronary artery angiography (CAG) and 24h-ABPM in this hospitalization were conducted. Exclusion criteria: (1) suffered an acute stroke or diagnosed as acute myocardial infarction, old myocardial infarction in the past or this hospitalization, (2) previously underwent CCTA, CAG, coronary stent implantation or coronary artery bypass grafting, (3) diagnosed as sleep apnea syndrome or had irregular hours like shift work, (4) evidence of secondary hypertension, (5) had incomplete medical records. Depending on CCTA or CAG, the CAD group involved patients who had ≥ 50% diameter narrowing of at least 1 major coronary artery including the left main coronary artery, left anterior descending branch, left circumflex branch, and right coronary artery [8]. The non-CAD group had normal coronary artery or lesions with ＜50% diametral stenosis.

24h-ABPM assessment

Use a portable BP monitoring device (SpaceLabs 90207/90217; SpaceLabs Medical, Redmond, Washington, USA) with a standard cuff or a “fat” cuff if necessary for 24 hours to measure ambulatory BP. In case of interfering with sleeping and daily life and affecting the results of BP rhythm, the device was set to measure every 30 minutes in the daytime (7:00 am to 11:00 pm) and every 60 minutes at bedtime (11:00 pm to 7:00 am the next day). If no BP was recorded in 2 hours or the BP error/loss value was more than 10%, the participant was excluded for incomplete data. The data of 24-hour mean systolic and diastolic BP (SBP-24, DBP-24), daytime mean systolic and diastolic BP (SBP-D, DBP-D), bedtime mean systolic and diastolic BP (SBP-B, DBP-B) were recorded. Nocturnal SBP decline rate (%) = (1－SBP-B / SBP-D) ×100, DBP decline rate (%) = (1－DBP-B / DBP-D) ×100, and BP rhythm was divided into 4 categories: dipper (10% < decline rate ≤ 20%, represent as D-SBP, D-DBP), non-dipper (0% < decline rate ≤10%, represent as ND-SBP, ND-DBP), reverse dipper (decline rate ≤ 0%, represent as RD-SBP, RD-DBP) and extreme dipper (decline rate > 20%, represent as ED-SBP, ED-DBP). Abnormal rhythm included above 4 categories excluded dipper represent as AR-SBP, AR-DBP.

Clinical and laboratory data collection

(1) General information: age, gender, height, weight, body mass index (BMI), smoking history, drinking history, level and course of hypertension, and course of diabetes were recorded. The information was provided by the patient himself or an informed family member, and the patient was informed that the data would be used for clinical research, and consent was obtained. When measuring height and weight, the subject took off his coat and shoes. OMRON HNH-219 ultrasonic weight instrument was used to measure gross weight and net body height. The measurement results were reported on-site and the BMI value was calculated automatically.

(2) Laboratory measurements: fasting plasma glucose (FPG), glycosylated hemoglobin TypeA1C (HbA1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine (Cr) were recorded. The blood samples of the patient were collected in the morning after a light diet and fasting for 8-12 hours on the day before and were sent to the clinical laboratory in time to obtain corresponding data.

(3) Office BP: at admission, the patient was seated vertically and rested for 15 minutes quietly in accordance with the Standard Joint National Committee VII, average of three consecutive recordings made per minute was called office SBP and office DBP which were measured by Omron BP monitor (Omron Healthcare, Vernon Hills, Illinois, USA).

Statistical analysis

SPSS 26.0 statistical software was used for data processing and analysis. The Kolmogorov-Smirnov test was used to verify whether the continuous variables were under the normal distribution, and those under the normal distribution were expressed as mean ± standard deviation. The independent sample T-test was used for inter-group comparison. Non-normal distribution parameters were represented by median and quartile (P50 (P25, P75)), and the Kruskal-Wallis test was used for comparison between groups. Categorical variables were expressed using composition ratios and compared through a chi-square test. Logistic regression was used to analyze the relationship between possible factors (all above clinical, laboratory, BP, and BP rhythm parameters) and CAD. Non-normal distribution data needed logarithmic transformation, and the statistically significant factors of CAD were included in the multivariate logistic regression model. P < 0.05 was considered to be statistically significant.

The mean age of a total of 853 subjects (414 CAD and 439 non-CAD) was 67 (60, 73), and 47.8% (n=408) of the participants were male. CAD group were older and more likely to be male, had more cigarette and alcohol hobbies, and showed a long history of hypertension and diabetes. They had lower BMI and HDL but higher HbA1c and Cr. No matter SBP-24, SBP-D, or SBP-B, it was higher in the CAD group, while DBP in 24h-ABPM had no significant difference (shown in table 1). Only a small number of diabetic patients had a dipper BP rhythm (D-SBP: 14.7%, n=125; D-DBP: 21%, n=179) and most diabetic patients had a non-dipper BP pattern in both CAD (ND-SBP: 45.7%, n=189; ND-DBP: 50.7%, n=210) and non-CAD (ND-SBP: 53.8%, n=236; ND-DBP: 48.5%, n=213) group no matter SBP or DBP. The nocturnal BP decline rate in CAD group was less than that in non-CAD group (SBP: 1.3% vs 3.7%, p＜0.001; DBP: 3.7% vs 5.2%, p＜0.001 ) , and even BP rising at night in not a few CAD patients (RD-SBP: 42.3%, n=175; RD-DBP: 30.9%, n=128). Diabetic patients with CAD had a higher percentage of RD-SBP and RD-DBP patterns than the non-CAD group (42.3% vs 27.6%, 30.9% vs 22.8%) (shown in figure 1).

Table 1. Baseline characteristics of patients.

Variable	All(n=853)	CAD(n=414)	Non-CAD(n=439)	P value
Clinical data
Age, years	67.0(60.0, 73.0)	68.0(62.0, 75.0)	66.0(58.0, 72.0)	<0.001
Male, n(%)	408(47.8)	215(51.9)	193(44.0)	0.020
Alcohol abuse, n (%)	199(23.3)	110(26.6)	89(20.3)	0.030
Smoking, n (%)	278(32.6)	156(37.7)	122(27.8)	0.002
HP course, years	5.0(0,10.0)	7.0(1.0,11.3)	5.0(0,10.0)	0.001
Diabetes course, years	4.0(0,10.0)	5.0(0, 10.0)	3.0(0,9.0)	<0.001
BMI, kg/m²	24.9(23.1,27.1)	24.5(22.7,26.6)	25.3(23.5,27.5)	<0.001
Office SBP, mmHg	141.0(127.0,155.0)	142.5(128.0,157.0)	140(126,153)	0.203
Office DBP, mmHg	82.0(74.0,91.0)	80.0(72.0,90.0)	83.0(75.0,93.0)	0.031
Laboratory data
HbA1c, %	7.0(6.4,8.0)	7.1(6.5,8.0)	6.9(6.3,7.7)	<0.001
FPG, mmol/L	7.0(6.0,8.7)	7.2(6.5,8.3)	6.9(6.0,8.7)	0.739
TG, mmol/L	1.6(1.2,2.3)	1.6(1.2,2.4)	1.5(1.2,2.2)	0.425
TC, mmol/L	4.6(3.8,5.4)	4.7(3.7,5.5)	4.5(3.8,5.4)	0.372
HDL, mmol/L	1.1(1.0,1.3)	1.1(0.9,1.3)	1.2(1.0,1.4)	0.022
LDL, mmol/L	2.3(1.8,2.9)	2.4(1.8,3.0)	2.3(1.8,2.9)	0.094
Cr, mmol/L	65.4(53.8,80.8)	68.3(55.9,84.7)	62.9(51.5,75.8)	<0.001
24h-ABPM results
SBP-24, mmHg	125.6±14.8	127.4±14.5	124.0±14.8	0.001
SBP-D, mmHg	126.0(116.0,136.0)	127.0(117.0,137.0)	124.0(115.0,134.0)	0.025
SBP-B, mmHg	122.0(112.0,134.0)	125.0(115.0,137.0)	119.0(110.0,132.0)	<0.001
DBP-24, mmHg	74.7±10.7	74.3±10.3	75.1±11.2	0.282
DBP-D, mmHg	75.0(68.0,83.0)	75.0(68.0,82.3)	75.0(68.0,83.0)	0.304
DBP-B, mmHg	72.0±11.4	72.3±10.8	71.7±11.9	0.482
SBP decline rate, %	2.6(-2.5,7.4)	1.3(-4.4,6.1)	3.7(-0.5,8.5)	<0.001
D-SBP, n (%)	125(14.7)	48(11.6)	77(17.5)	-
ND-SBP, n (%)	425(49.8)	189(45.6)	236(53.8)	-
RD-SBP, n (%)	296(34.7)	175(42.3)	121(27.6)	-
ED-SBP, n (%)	7(0.8)	2(0.5)	5(1.1)	-
DBP decline rate, %	4.4(-0.6,9.8)	3.7(-1.7,8.4)	5.2(0.2,11.0)	0.002
D-DBP, n (%)	179(21.0)	67(16.2)	112(25.5)	-
ND-DBP, n (%)	423(49.6)	210(50.7)	213(48.5)	-
RD-DBP, n (%)	228(26.7)	128(30.9)	100(22.8)	-
ED-DBP, n (%)	23(2.7)	9(2.2)	14(3.2)	-

Results are presented as median and quartile (P50 (P25, P75)), mean±standard deviation, or n (%). The P values represent the difference between CAD and non-CAD. HP: Hypertension; BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HbA1c: Glycosylated hemoglobin, TypeA1C; FPG: Fasting plasma glucose; TG: Triglyceride; TC: Total cholesterol; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; Cr: Creatinine.

There were 38.4% D-SBP, 44.5% ND-SBP, 59.1% RD-SBP, and 28.6% ED-SBP diabetic patients who suffered CAD. The CAD morbidity was statistically significantly higher in RD-SBP than in the D-SBP group (P<0.001), RD-SBP than ND-SBP group (P<0.001). While 37.4% D-DBP, 49.6% ND-DBP, 56.1% RD-DBP, 39.1% ED-DBP patients had CAD, CAD morbidity was higher in RD-DBP than D-DBP group (P<0.001), ND-DBP than D-DBP group (p=0.006) (showed in figure 2).

In univariate analysis, the factors statistically significant related to CAD were age ( OR=1.030, P<0.001), male (OR=1.377, P=0.020), smoking (OR=1.571, P=0.002), alcohol abuse (OR=1.423, P=0.030), level (OR=1.208, P=0.002) and course (OR=1.022, P=0.007) of hypertension, course of diabetes (OR=1.043, P<0.001), BMI (OR=0.927, P<0.001), HbA1c (OR=1.121, P=0.009), HDL (OR=0.641, P=0.046), Cr (OR=1.010, P<0.001), SBP-24 (OR=1.016, P=0.001), SBP-B (OR=1.021, P<0.001), AR-SBP (OR=1.622, P=0.015), AR-DBP (OR=1.774, P=0.001), RD-SBP (OR=2.320, P<0.001), RD-DBP (OR=2.140, P<0.001), and ND-DBP (OR=1.648, P=0.006). For further multivariate logistic analysis, above abnormal BP pattern was still significantly related to CAD in model 1 and model 2 (showed in figure 3).

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 [4], while another clinical study conducted in South China put that it was not RD-SBP but RD-DBP that increased the risk of CAD [3]. 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 [18].

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 [15], it was also shown in our study. This mutually reinforcing association might increase the risk of CAD [19]. 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 [1]. 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 [7]. 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 [20]. Non-dipper BP was associated with increased sympathetic nervous activity and decreased parasympathetic nervous activity, which increased mortality in subjects [21].

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 [22]. Yu-Sok Kim proposed that the non-dipper BP pattern in diabetic patients was associated with microangiopathy but not autonomic neuropathy [19]. We knew that there were higher levels of inflammatory markers, high platelet activity, and hypercoagulable state in patients with diabetes [23], 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 [12]. On the other hand, the platelet activity was increased and the inflammatory reaction was heavy in non-dipper patients [24]. 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 [25]. Further analysis found that polymorphisms of genes related to CAD (MIA3、MEAS、PCSK9、SMG6、ZC3HC1) were associated with AR-SBP and AR-DBP [26]. 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[3]. Other studies suggested that the timing of medication-taking makes sense[14], 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 [29], and when changed from dipeptidyl peptidase-4 inhibitor to SGLT2i, the AR-BP significantly reduced [30]. 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.

In conclusion, abnormal BP rhythm, especially reverse dipper pattern may be a risk factor for CAD regardless of SBP or DBP in diabetic patients. While for non-dipper, only the non-dipper DBP pattern had a risky influence.

CAD: Coronary artery disease; AR: Abnormal rhythm; BP: Blood pressure; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; D: Dipper; ND: Non-dipper; RD: Reverse dipper; ED: Extreme dipper; 24h-ABPM: 24-hour ambulatory blood pressure monitoring; AR-BP: Abnormal rhythm of blood pressure; CCTA: Coronary computed tomography angiography; CAG: Coronary artery angiography; SBP-24: 24-hour mean systolic blood pressure; DBP-24: 24-hour mean diastolic blood pressure; SBP-D: Daytime mean systolic blood pressure; DBP-D: Daytime mean diastolic blood pressure; SBP-B: Bedtime mean systolic blood pressure; DBP-B: Bedtime mean diastolic blood pressure; D-SBP: Dipper of systolic blood pressure; D-DBP: Dipper of diastolic blood pressure; ND-SBP: Non-dipper of systolic blood pressure; ND-DBP: Non-dipper of diastolic blood pressure; RD-SBP: Reverse dipper of systolic blood pressure; RD-DBP: Reverse dipper of diastolic blood pressure; ED-SBP: Extreme dipper of systolic blood pressure; ED-DBP: Extreme dipper of diastolic blood pressure; AR-SBP: Abnormal rhythm of systolic blood pressure; AR-DBP: Abnormal rhythm of diastolic blood pressure; BMI: Body mass index; FPG: Fasting plasma glucose; HbA1c: Glycosylated hemoglobin, TypeA1C; TG: Triglyceride; TC: Total cholesterol; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; Cr: Creatinine; SGLT2i: Sodium-dependent glucose transporters 2 inhibitor.

Ethics approval and consent to participate: This study was approved by the Ethics Committee of The Second Affiliated Hospital of Chongqing Medical University and conducted in accordance with the Declaration of Helsinki (2013 edition). Due to the retrospective nature of the research, the need for informed consent was waived.

Consent for publication: Not applicable.

Availability of data and materials: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests: The authors declare that they have no competing interests.

Funding: Not applicable.

Authors' contributions: QLW designed the study and wrote the manuscript, DL and JCY collected data, XYX and XYW performed the statistical analysis. LS conceptualized the study and revised the manuscript. All authors reviewed and approved the final version of the manuscript.

Acknowledgments: The authors thank all patients of the project for their participation and the geriatricians for providing partial clinical records

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No competing interests reported.

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Effects of systolic and diastolic blood pressure rhythm on coronary artery disease in type 2 diabetic patients: a retrospective cross-sectional study

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