Hypertension (HTN) is quite a common medical condition/ disorder where the force of the blood against artery walls reach to high level. It is one of the multifactorial contributors in the cardiovascular diseases (CVDs) [1]. Whereas the Chronic Bronchitis (CB), a primary type of Chronic Obstructive Pulmonary Disease (COPD) is a long-term inflammatory disorder of respiratory passageways causing productive cough on daily basis for few months continuing to two successive years. It is a primary type of Chronic Obstructive Pulmonary Disease (COPD) [2].   Blood markers in HTN are sodium, potassium, creatinine, estimated glomerular filtration rate (eGFR), other markers related to kidney function, fasting blood glucose (FBG)/or glycated hemoglobin A1C (HbA1c) and lipid profile [3-5]. Some of the other markers for secondary causes are Thyroid-Stimulating Hormone (TSH), aldosterone and renin [6].   Important pathophysiological mechanisms of the occurrence of CB are ciliary dysfunction that destroy the mucociliary escalator, mucus hypersecretion that triggers hypertrophy and hyperplasia in the cartilaginous submucosal glands, airway obstruction/gas mismatch that causes hypoxemia, air-trapping and hypercapnia, airway inflammation/fibrosis causing activation of innate and adaptive immunity, release of pro-inflammatory cytokines leading to edema, hyperplasia in smooth muscles/ peribranchial fibrosis and vascular dysfunction that increases the vascular resistance and may lead to right-sided heart failure [2,7].   There are a number of factors involved in the pathogenesis of CB and HTN. Low Density Lipoprotein Cholesterol (LDL-C) and cell free deoxyribonucleic acid (cfDNA) are the two important risk factors in the occurrence of CB and HTN. However, in view of inconclusive and controversial reports, we planned to determine various variables including age, Basal Body Temperature (BBT), Hemoglobin (Hb), Fasting Blood Glucose (FBG), Hepcidin (Hp), LDL-C and cfDNA. However, the main emphasis in the present study was to assess the impact of the variations and association of LDL-C and cfDNA in hypertension and chronic bronchitis in adult men.

The present study was conducted following the ethical considerations of the World Medical Association (WMA) Declaration of Helsinki and accepted/approved by Ethical Committee, College of Medicine, Umm Al-Qura University (UQU), Makkah, Saudi Arabia, Approval Number: “HAPO‐02‐K‐012‐2022‐01‐1085.” Furthermore, written consent was taken from each of the participants. Research studies were started on April 26, 2023 and were completed in January 27, 2026 in the nearby hospitals affiliated with UQU.   Sample size was determined using the formula and confirmed by calculator method. Comprehensive history and interviews of the participants were conducted and the information was saved for assessment and analysis. Two groups of patients, HTN and CB, were studied in the present work. A third group served as a Normal Control (NC) group for comparison purpose. Age of all participants was between 51 and 60 years. Participants having less or more age than the mentioned range were not included in the current study. The BMI (kg/m2) was determined by dividing the body weight (BW) in kilograms of the participants by squared values of body height in meters.   Participants having normal weight BMI (kg/m2) of 18.5 to 24.9 were included in the present study. Consent of each participant was obtained for collecting information about their disease, previous and present medication, family and their personal background and blood collection. Present study did not involve the overweight and obese participants. Patients having serious disorders (other CVDs, diabetes, stroke, metabolic syndrome (MetS) etc) were not dealt in the present study.   Oral basal body temperature (BBT, °F) was determined employing a Citizen Digital Thermometer CTA303 from Taipei, Taiwan (water resistant, antibacterial and washable). The fasting blood glucose (FBG, mg/dL) test required to take the blood sample at least 10 hours from the last meal. The hepcidin (Hp, ng/mL) was assessed by kit method-Human Hp enzyme-linked immunosorbent assay (ELISA) kit (MyBioSource, Inc, San Diego, CA, United States (US) employing ELISA reader. The hemoglobin (Hb, g/dL) levels were measured using a hematology analyser-Sysmex XN 100i (Sysmex Europe SE, Norderstedbt; Germany).   Some of the common symptoms of chronic bronchitis are shortness of breath specially while doing a physical activity, wheezing, chest pain, production of mucus that is clear, white, green or yellow and occurrence of tiredness or fatigue [2].   Hypertension is clinically diagnosed employing Blood Pressure (BP) cuffs with readings, not by blood tests, though the baseline blood levels of biomarkers are checked to confirm for determining the underlying causes especially the kidney and heart diseases [5].   The HTN is often called as the silent killer since HTN develops noticeable warning/signs rarely leading to a severe manifestation. If the HTN is not treated, it may significantly increase the risk of having cardiac attacks, kidney damages, strokes and other complications.   The BP was determined in mmHg (millimeters of mercury) for systolic BP (SBP) and diastolic BP (DBP) where 120/80,120-129/≤80,130-139/80-89 and ≥140/≥90 are respectively normal BP, elevated BP, stage-1 HTN and stage-2 HTN. The ELISA (enzyme‐linked immunosorbent assay) kits were used for determining LDL-C (mg/dL), cfDNA (ng/mL) and other variables in the present study.   SPSS (Statistical Package for Social Sciences, version 24.0 for Windows (SPSS Inc., Chicago, IL, USA) as well as GraphPad Prism (version 6.0), San Diego, CA, USA, were employed for the analyzing the present data. Values in mean±SD were determined and analyzed for obtaining their variation/ difference using unpaired t-test for two tailed values of p. Whereas the associations/ correlations were obtained by drawing the regression lines and finding the R2 for respective p-values (p<0.05 was standardized as a significant variation).

The present study was conducted to find out the impact and association of LDL-cholesterol and cfDNA in adult male patients with hypertension and chronic bronchitis, both groups of patients compared with a group of the normal healthy male participants having same range of age and BMI.   The data of age (years), BBT(°F), BMI (kg/m2), Hb (g/dL), FBG (mg/dL) and Hp (ng/mL) (Table 1) did not show any significant difference (p>0.05) for patients of both groups (HTN and CB) compared with NC. The LDL-C and cfDNA in patients with CB compared with NC also did not present any significant variation (p>0.05). The serum LDL-C and cfDNA in HTN patients compared to NC showed significant variation (<0.001) (Table 1).   Table 1: Characteristic Features and Parameters in Normal Adult Male Healthy Controls and Patients with Hypertension and Chronic Bronchitis Parameters Normal adult male healthy controls and patients with hypertension and chronic bronchitis NC CB Significance (p) (CB vs. NC) HTN Significance (p) (HTN vs. NC) Age (years) 55.12±2.96 55.13±2.97 0.98 55.23±2.89 0.77 BBT (°F) 98.61±0.68 98.59±0.66 0.81 98.62±0.69 0.91 BMI (kg/m2) 21.64±2.09 21.63±2.07 0.97 21.69±2.08 0.85 Hb (g/dL) 13.83±1.17 13.83±1.15 0.98 13.84±1.17 0.97 FBG (mg/dL) 91.52±3.28 91.58±3.38 0.88 91.93±4.01 0.37 Hp (ng/mL) 9.49±4.69 9.58±4.74 0.87 9.71±4.85 0.71 LDL-C (mg/dL) 95.78±7.76 97.08±8.06 0.19 103.91±12.98 <0.001 cfDNA (ng/mL) 110.46±64.31 116.16±63.99 0.47 158.73±95.60 <0.001   Serum LDL-C of CB, HTN and NC groups was plotted against other variables of age, BBT, Hb, FBG and Hp that showed non-significant correlation. The LDL-C against cfDNA for HTN group of patients presented significant positive linear correlation (p<0.001; Table 2).   Table 2: Correlation of LDL-C with Other Parameters in Normal Adult Male Healthy Controls and Patients with Hypertension and Chronic Bronchitis Parameters Correlation of LDL-C with other parameters in normal adult male healthy controls and patients with hypertension and chronic bronchitis NC HTN CB R2 P R2 p R2 p Age 0.003 0.558 0.002 0.641 0.000 0.824 Hb 0.007 0.351 0.016 0.158 0.005 0.421 FBG 0.005 0.158 0.027 0.064 0.012 0.216 Hp 0.000 0.976 0.001 0.730 0.001 0.715 cfDNA 0.00 0.93 0.80 <0.001 0.00 0.76   Serum cfDNA of CB, HTN and NC groups was plotted against age, BBT, Hb, FBG and Hp that showed non-significant correlation. The cfDNA against LDL-C for HTN group of patients presented significant positive linear correlation (p<0.001; Table 3).   Table 3: Correlation of cfDNA with Other Parameters in Normal Adult Male Healthy Controls and Patients with Hypertension and Chronic Bronchitis Parameters Correlation of cfDNA with other parameters in normal adult male healthy controls and patients with hypertension and chronic bronchitis NC HTN CB R2 p R2 p R2 p Age 0.000 0.990 0.002 0.613 0.001 0.692 Hb 0.000 0.912 0.007 0.332 0.001 0.793 FBG 0.001 0.768 0.017 0.137 0.004 0.501 Hp 0.021 0.098 0.001 0.687 0.017 0.134 LDL-C 0.00 0.93 0.80 <0.001 0.00 0.76

Both groups of male adult patients (HTN and CB) compared with a group of normal healthy adult male participants in the present study had same range of age and Body Mass Index (BMI). The LDL-C and cfDNA in patients with CB compared with NC did not present any significant variation (p>0.05). The HTN group of patients showed significant variation for LDL-C levels compared to NC levels (<0.001) and cfDNA levels compared to NC levels (<0.001). Furthermore, the LDL-C levels plotted against cfDNA levels for HTN group of patients presented significant positive linear correlation (p<0.001). Plot of LDL-C levels against cfDNA levels in CB group and association of all other variables with LDL-c as well as cfDNA in both groups (HTN and CB) of patients showed non-significant correlations.   Our findings mentioned in the above paragraph can be explained with the following reports. It is known that HTN develops inflammation and vice versa and it has been noticed that inflammatory/oxidative stressful conditions are linked to HTN,8 though the clinical/preclinical studies explain that O2 generation/systemic oxidative stress are present before the development of significant elevated BP that converts prehypertension (Pre-HTN) to HTN [9]. It was found that elderly people have more incidence of arterial stiffness (AS), HTN and other CVDs involving inflammation [10].   The vascular disorders that relate to endothelial dysfunction [11] have a strong relatedness with inflammatory/oxidative conditions and HTN [12]. Furthermore, in view of the imbalance between vasoconstrictor and vasodilatory activities, the AS occurs that leads to elevation of BP owing to elevated vascular resistance.13 Nitric oxide increases vasodilation but with the increase in age toward old age and increase in BP, endothelial vasoactive substances are released causing vasodilation of vessels [12,13]. The HTN incidence increases with age [14]. However, the present study was not conducted for age-wise variations and associations. The HTN was higher in men till age 45 years than in women [14] and have similar incidence rate after 46 till 64 and females have more incidence rate than men after 65 [15]. These changes are primarily due to sex hormones, chromosomal features and other sex differences providing protective actions in females [16]. But since the present study was conducted only in adult men, it cannot be compared and explained for gender differences.   The HTN may develop due to a variety of factors including cholesterol [17] and especially the LDL-C [18-20]. Several reports [18-20] provide evidence for the impact of the findings in the current study. The LDL-C concentration and risk of CVDs have an association [21]. Higher concentrations of LDL-C [22-24] and cfDNA in HTN were obtained [25-28]. Elevated blood LDL-C levels besides alterations in other lipid profile variables were revealed in patients with HTN than healthy NC [29].   There are studies showing no significant alteration of LDL-C rather remnant cholesterol in middle aged and elderly patients with HTN [30,31] and no significant change in cfDNA in HTN [26]. It is possible that the HTN patients in the mentioned studies were having mild and varying forms of symptoms and were having other comorbidities that might had influenced the levels of LDL-C and cfDNA.   A number of blood markers are considered important in CB. Some of them are, C-reactive protein (CRP), abnormal high number of red blood cells (RBCs) (polycythemia), high neutrophils, hypoxemia and respiratory acidosis related to arterial blood gas (ABG) and alpha-1 antitrypsin that helps checking the genetic disorder causing emphysema [32]. There are reports that indicate the impact of LDL-C [33] and cfDNA [34] in CB.   Clinical and meta-analyses studies in CB show non-significant differences and associations for LDL-C while comparing with controls [33,35,36] and non-significant difference of cfDNA in CB patients compared to normal healthy controls [37-39]. These studies provide excellent information for interpreting the presently obtained results in patients with HTN and CB.

The present report provides the information of the significant impact of increased levels and positive linear correlation of serum LDL-C and cfDNA in adult patients with HTN, involving the risk factors, especially the inflammatory conditions. Increase in BP may increase LDL-C and cfDNA and vice versa via tissue damage and inflammation.   Acknowledgement Authors are thankful to the laboratory experts and medical experts/consultants for their invaluable support.   Ethical Considerations The present study was conducted following the ethical considerations of the WMA Declaration of Helsinki and accepted/approved by Ethical Committee, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; Approval Number: “HAPO‐02‐K‐012‐2022‐01‐1085.” Furthermore, written consent was taken from each of the participants.