Coronavirus disease 2019 (COVID-19) remains a health problem worldwide. The present study aimed to investigate the effect of blood pressure (BP) on the circadian pattern and prevalence of new-onset non-dipper hypertension in the post-COVID period in patients with known hypertension. This prospective single-center study included 722 patients hospitalized for COVID-19 infection. Ambulatory BP (ABP) data were collected during their initial hospitalization. The ABP data were reassessed 1 month after the patients were discharged. The results were compared with a healthy control group with known hypertension but without COVID-19 infection. After exclusion criteria were applied, the study included 187 patients with COVID-19 and 136 healthy hypertensive controls. Post-COVID ABP showed that patients with COVID-19 had significantly higher mean 24-h systolic and diastolic BP, mean nighttime systolic and diastolic BP, and mean daytime diastolic BP than the control group. In addition, new-onset non-dipper hypertension was significantly higher in patients with COVID-19. This study demonstrated for the first time that the circadian pattern is disturbed and a non-dipper pattern develops in individuals with known hypertension during the post-COVID period.

This study aimed to probe the effects of low-dose irbesartan and hydrochlorothiazide in combination with levamlodipine at different times on the circadian rhythm of blood pressure, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) levels in patients with non-dipper hypertension (NDH). In this prospective randomized controlled trial, 124 patients with NDH who visited our hospital between August 2018 and July 2021 were enrolled and divided into morning (62 patients) and night (62 patients) medication groups according to the random number table method. All patients received low-dose irbesartan and hydrochlorothiazide combined with levamlodipine, with the morning medication group taking the medication between 7:00 and 10:00 and the night medication group taking the medication between 19:00 and 22:00 for 24 weeks. The effect of antihypertensive medication in both groups was measured, and changes in ambulatory blood pressure, blood pressure circadian rhythm, left ventricular structure, vascular endothelial function, MMPs, and TIMPs levels were observed before treatment initiation and after 24 weeks of treatment in both groups. The percentage of the dipper type was higher in the night medication group than in the morning medication group, while the percentage of the non-dipper type was lower in the morning medication group (p < .05). Low-dose irbesartan and hydrochlorothiazide combined with levamlodipine at different times can effectively treat NDH, but bedtime dosing is more beneficial in reducing nocturnal blood pressure, reversing NDH, improving the circadian rhythm of blood pressure, left ventricular structure, regulating vascular endothelial function, increasing MMPs levels, and reducing TIMP levels.

OBJECTIVE: To evaluate the association between non-dipper blood pressure pattern and subconjunctival hemorrhage (SCH).
METHODS: Twenty-seven consecutive patients with nocturnal SCH and 27 age, sex-matched controls were enrolled. Demographic, blood parameters, office blood pressure measurements, 24-h ambulatory blood pressure monitoring (ABPM) were evaluated.
RESULTS: Mean diastolic blood pressure (DBP) for nighttime (65.03 ± 7.1 vs. 70.78 ± 10.5, p: 0.22), mean heart rate for nighttime (64.54 ± 8.26 vs. 69.93 ± 9.85, p: 0.034), Minimum Systolic Blood pressure(SBP) and DBP values for nighttime (92.44 ± 9.72 vs. 99.44 ± 10.66, p:0.015 and 51.15 ± 8.31 vs. 57.7 ± 11.2, p: 0.018) were higher, nocturnal fall ratio of SBP and DBP were significantly lower in the SCH ( + ) group compared to SCH (-) group (5.38 ± 8.39 vs. 10.34 ± 6.08, p: 0.016 and 4.26 ± 8.92 vs. 13.78 ± 6.97, p < 0001 respectively). Ten patients (37%) in the SCH (-) group and 18 patients (66.7%) in the SCH ( + ) group were non-dippers (p: 0.029). Mean daytime SBP and DBP were higher compared to office measurements of 4 patients (14.8%) in the SCH (-) group and 11 patients (40.7%) in the SCH ( + ) group (p: 0.033).
CONCLUSIONS: SCH had a strong association with non-dipper blood pressure pattern, higher nocturnal heart rate and masked hypertension which are precursors of myocardial infarction, stroke and renal failure. So, SCH should be considered as a clue for serious diseases such as coronary artery disease, myocardial infarction, stroke and patients should be evaluated for ABPM.

Background: Non-dipper hypertension is often characterized by a blunted decrease of nocturnal blood pressure (BP) and is associated with increased risk of target organ damage and cardiovascular (CV) events, while the optimal treatment strategy is yet to be established. This trial was designed to evaluate whether nocturnal BP reduction and arterial stiffness improvement differ from antihypertensive agents and time of administration. Methods: Young and middle-aged adults (18-65 years) with non-dipper hypertension were randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily for 8 weeks, either taken in the morning or at night. Dose was doubled at 4-week if BP is not at goal. Twenty-four hour ambulatory BP monitoring (ABPM) and arterial stiffness were evaluated before and after 8 weeks of pharmacotherapy. The primary efficacy measure was the average nighttime systolic BP reduction. Results: A total of 98 non-dipper hypertensive patients (mean age 46.3 years) were randomized during Dec, 2016 and Dec, 2020, of whom 72 (73%) patients completed all ABPM and follow-up evaluations. Nighttime systolic BP significantly reduced at 8 weeks vs. baseline with nifedipine GITS or amlodipine, irrespective of dosing at nighttime (-9.9 vs -9.9 mmHg, P > 0.05) or daytime (-11.5 vs. -10.9 mmHg, P > 0.05). No difference was seen between these two agents, when combining the data of nighttime and daytime dosing together (-10.8 vs. -10.5 mmHg, respectively, P = 0.898). Daytime, 24-h systolic BP, diastolic BP at different time and pulse wave velocity reduced significantly and comparably, and recovery of dipping rhythm were similar among groups. Conclusion: Nighttime dosing of long-acting antihypertensive preparations, nifedipine GITS or amlodipine demonstrated similar effects on nocturnal BP reduction, dipping rhythm restoration and arterial elasticity improvement in younger subjects with non-dipper hypertension. These effects were comparable with morning dosing.

It is known that non-dipper pattern (NDP) is associated with adverse outcomes in hypertensive patients. However, there is insufficient data on the outcome of NDP in normotensive individuals. Using myocardial work (MW) analysis, as a new echocardiographic examination method, this study aimed to determine the early myocardial effects of NDP in normotensive individuals.
This study included 70 normotensive individuals who were followed by ambulatory blood pressure monitoring (ABPM). The subjects were divided into two groups according to dipper pattern (DP) and NDP. Conventional, strain, and MW findings were compared between the groups by making echocardiographic evaluations.
The demographic characteristics, laboratory parameters, and measurements of cardiac chambers, and left ventricular (LV) walls were similar between the groups. There was no statistical difference between the groups in terms of LV 3-2-4 chambers strains and global longitudinal strain (GLS) values. LVMW parameters, global work index (GWI), and global constrictive work (GCW) were not statistically different between groups (2012 ± 127, 2069 ± 137, p = 0.16; 2327 ± 173, 2418 ± 296, p = 0.18, respectively). However, global waste work (GWW) and global work efficiency (GWE) parameters were different between the groups (144 ± 63.9, 104 ± 24.8, p < 0.001; 93.2 ± 3.17, 95.4 ± 1.28, p < 0.001, respectively). In regression analysis, GWW was independently associated with NDP. GWW model showed better results with higher likelihood chi-square and R2 values than GLS model in discriminating the predictable capability for NDP status.
The results of MW analysis in this study showed that GWW values were higher and the GWE values were lower in normotensive individuals with NDP.

Interleukin-37 (IL-37) has been reported to be closely linked to vascular diseases, including atherosclerosis and aortic calcification. The present study aimed to assess the expression levels of IL-37 in patients with hypertension. Blood samples were collected from control subjects (n=20) and patients with hypertension (n=45). Subsequently, macrophages, lymphocytes and dendritic cells were individually isolated and the mRNA expression of IL-37 was measured. In addition, the circulating IL-37 levels in control subjects (n=30) and patients with hypertension (n=334) were assessed. Furthermore, all patients who were subjected to detection of circulating IL-37 underwent ambulatory blood pressure monitoring. The results suggested that the mRNA levels of IL-37 in macrophages, but not in lymphocytes and dendritic cells, isolated from patients with hypertension were markedly elevated compared with those in cells isolated from control subjects. Circulating IL-37 levels were increased in patients with hypertension compared with those in control subjects and positively correlated with systolic and diastolic blood pressure in patients with hypertension. No differences were observed between patients with dipper hypertension and patients with non-dipper hypertension. In addition, patients with hypertension with a smoking habit, type 2 diabetes mellitus and carotid atherosclerotic plaque (CAP) exhibited higher IL-37 levels. IL-37 levels were positively correlated with creatinine, C-reactive protein and homocysteine levels. Furthermore, the results of a linear regression analysis suggested that IL-37 levels were independently associated with the presence of CAP. In conclusion, IL-37 levels are increased in patients with hypertension and may be associated with the onset of CAP.

Background and Objectives: The mean platelet volume (MPV) represents a possible marker of platelet activation. There is an association between the platelet count (PC) and inflammation and platelet reactivity. We assessed the association between the MPV/PC ratio and circadian alterations in blood pressure (BP). Material and Methods: One hundred and twenty subjects in total, 80 hypertensive subjects and 40 healthy subjects (controls), were enrolled in the study group. Twenty four hour ambulatory BP monitoring (ABPM) was applied to all subjects. According to ABPM results, the hypertensive subjects were separated into two groups, such as dippers (n = 40) and non-dippers (n = 40). In all subjects, the collection of venous peripheral blood samples was performed on admission for PC and MPV measurements. Results: The two groups exhibited similar clinical baseline characteristics. A significantly higher MPV/PC ratio was determined in non-dippers compared to that in dippers and normotensives. The higher MPV/PC ratio was observed in non-dippers in comparison with that in dippers and normotensives (0.046 ± 0.007 to 0.032 ± 0.004 fL/[109/L]; 0.046 ± 0.007 to 0.026 ± 0.004 fL/[109/L], p < 0.001, respectively). A receiver operating characteristic (ROC) curve analysis showed that the optimum cut-off value of the MPV/PC ratio for predicting non-dipping patterns in hypertensive patients was 0.036 (area under the curve [AUC]: 0.98, p < 0.001). According to the cut-off value, sensitivity and specificity were found to be 95% and 95%, respectively. Conclusions: The higher MPV/PC ratio was determined in non-dipper hypertensive subjects in comparison with that in dipper hypertensive subjects. An elevation of platelet activity and an increase in thrombus burden are reflected by an increase in the MPV/PC ratio. The MPV/PC ratio may underlie the increase in cardiovascular risk in non-dippers compared to that in dippers.

Non-dipper hypertension (HT) confers greater risk compared with dipper HT. Growth differentiation factor 15 (GDF-15) recently emerged as a novel and independent marker of cardiovascular disease, both in diagnostic and prognostic scopes. Our aim was to evaluate the relationship of circadian blood pressure (BP) pattern with serum GDF-15 level in newly diagnosed HT patients without left ventricular hypertrophy.
Newly diagnosed non-dipper (n = 66) and dipper (n = 60) HT patients were selected according to 24-h ambulatory BP monitoring (ABPM). The controls comprised healthy normotensive subjects (n = 31). Data was collected through physical examination, laboratory analysis, ABPM, and echocardiography. GDF-15 was measured using ELISA.
Greater GDF-15 level was found in the non-dippers compared with the dippers and the controls (557.53 ± 91.7, 513.79 ± 62.86, and 494.44 ± 79.30 ng/L, respectively, p < 0.001). In bivariate linear correlation analysis, GDF-15 correlated positively with glomerular filtration rate (r = 0.180, p =0.030), total cholesterol (r = 0.170, p = 0.038), septal E/E\' ratio (r = 0.344, p = 0.001), lateral E/E\' ratio (r = 0.366, p < 0.001), nighttime systolic BP (r = 0.166, p = 0.046), and nighttime diastolic BP (r = 0.188, p = 0.024); however, it correlated negatively with septal and lateral E\' velocities (r = 0.268, p = 0.005 and r = 0.236, p = 0.013, respectively). Furthermore, GDF-15 level and nighttime diastolic BP remained independently associated with non-dipper HT. In ROC analysis, optimal cutoff value for GDF-15 was 524.6 ng/L with 56.7% sensitivity and 72.4% specificity (AUC: 0.676, 95% CI: 0.580-0.772, p < 0.05).
Our results showed GDF-15 upregulation in the non-dipper HT group. GDF-15 and nighttime diastolic BP were independently associated with the non-dipping pattern. This study may suggest possible utilization of GDF-15 in the prediction of non-dipper HT.

Background: Numerous clinical studies have evaluated valsartan and found more efficacious control of blood pressure (BP) variability when administered before sleep. The treatment leads to improved outcomes when compared to administration upon awakening. The mechanism underlying this etiology is not fully understood. The present study investigates the safety and efficacy of asleep administration of valsartan in spontaneously hypertensive rats (SHR) with a non-dipping blood pressure pattern compared to SHRs receiving administration during awake time. Materials and Methods: 84 Male SHRs and 28 male Wistar-Kyoto rats (WKY) were kept under a strict alternating 12-h light/dark cycle. WKYs were utilized as a non-disease control. Meanwhile, SHRs were randomly divided into three groups: untreated, Valsartan asleep administration (VSA) and Valsartan awake administration (VWA) respectively. The VSA group was treated with valsartan (30 mg/kg/d) after the light onset, while the VWA group was treated with valsartan (30 mg/kg/d) after light offset. Both groups were treated for 6 weeks. Tail artery blood pressure was measured every 4 h via a noninvasive tail cuff blood pressure measurement method. HE and Masson staining were used to evaluate any damage within the target organs. ELISA was used to determine the 24-h plasma renin-angiotensin system (RAS) concentration at 4-h intervals. Results: Based on our findings, VSA significantly reduced 24-h and evening mean BP and restored the abnormal circadian rhythm compared to VWA, which attenuated injuries in the majority of target organs except for the kidneys. Furthermore, VSA was found to activate RAS during the light cycle and inhibit it during the dark cycle. Conversely, VWA was found to deactivate RAS throughout the day which may be related to the circadian BP rhythm. Conclusion: VSA may be more efficacious than VWA in controlling BP, circadian BP rhythm and blood RAS rhythm. Recent cardiovascular outcome investigations substantiate that chronotherapy treatment might be a novel therapeutic strategy for hypertension therapy. Abbreviations: Angiotensin-converting enzyme (ACE); Angiotensin converting enzyme inhibitors (ACEIs); Angiotensin II (ANG II); Analysis of variance (ANOVA); Angiotensin receptor blockers (ARBs); Blood Pressure (BP); Calcium Antagonists Calcium Channel Blockers (CCB); Chronic kidney diseases (CKD); Sodium carboxyl methyl cellulose (CMC-Na); Cardiac mass index (CMI); Cardiovascular diseases (CVD); Diastolic blood pressure (DBP); Enzyme-linked immunosorbent assay (ELISA); Hematoxylin-eosin (H&E); Kidney mass index (KMI); Liver mass index (LMI); Mean arterial blood pressure (MAP); Plasma renin concentration (PRC); Renin-angiotensin system (RAS); Rennin (REN); Systolic blood pressure (SBP); Student-Newman-Keuls q test (SNK-q test); Spontaneous hypertension rats (SHR); Valsartan asleep Administration (VSA); Valsartan awake Administration (VWA); Wistar-Kyoto (WKY); Mesor (M); Amplitude (A); Phase (φ).

BACKGROUND: Endothelial dysfunction is one of the main pathological processes of hypertension. The association of serum pentraxin-3 (PTX3) levels and endothelial dysfunction becomes a more interesting scientific research issue due to high potential of PTX3 as a diagnostic and prognostic biomarker. We aimed to investigate the relationship between serum PTX3 levels and flow-mediated dilation results in patients with dipper and non-dipper hypertension.
METHODS: This study included 90 hypertensive patients were divided into two groups based on 24 hours ambulatory blood pressure monitoring (ABPM): 38 patients with a dipper pattern and 52 patients with non-dipper pattern. Noninvasive evaluation of the endothelial functions was performed using flow-mediated dilation (FMD) method.
RESULTS: Serum pentraxin-3 levels were higher in patients with non-dipper HT compared to dipper hypertension (P = 0.028). In addition, we found negative correlation between serum PTX3 and FMD basal/FMD hyperemia ratio (r = -0.297, P = 0.05 for FMD basal/FMD hyperemia ratio, respectively).
CONCLUSIONS: Serum PTX3 levels are closely related with the measures of indirect noninvasive evaluation methods (FMD) in both DH and NDH patients.