Hypertension Drug Research Articles

Nitroprusside and metal nitroprusside nano analogues for cancer therapy.

Sodium nitroprusside (SNP), U.S approved drug has been used in clinical emergency as a hypertensive drug for more than a decade. It is well established for its various biomedical applications such as angiogenesis, wound healing, neurological disorders including anti-microbial applications etc. Apart from that, SNP have been considered as excellent biomedical materials for its use as anti-cancer agent because of its behavior as NO-donor. Recent reports suggest that incorporation of metals in SNP/encapsulation of SNP in metal nanoparticles (metal nitroprusside analogues) shows better therapeutic anti-cancer activity. Although there are numerous reports available regarding the biological applications of SNP and metal-based SNP analogue nanoparticles, unfortunately there is not a single comprehensive review which highlights the anti-cancer activity of SNP and its derivative metal analogues in detail along with the future perspective. To this end, the present review article focuses the recent development of anti-cancer activity of SNP and metal-based SNP analogues, their plausible mechanism of action, current status. Furthermore, the future perspectives and challenges of these biomedical materials are also discussed. Overall, this review article represents a new perspective in the area of cancer nanomedicine that will attract a wider spectrum of scientific community.

Abstract A104: Losartan rewires ovarian cancer tumor-immune microenvironment and suppresses IGF-1 to amplify chemo-immunotherapy sensitivity

Abstract Background: Ovarian Cancer (OvCa) is the most lethal gynecologic malignancy worldwide. The use of immune checkpoint inhibitors (ICIs) has revolutionized the therapy of several malignancies. Unfortunately, ICIs have had limited efficacy in OvCa, with objective response rates in only 10 to 15% of patients. Prevailing preclinical and clinical data indicate that abnormalities in the tumor microenvironment (TME) contribute to immunosuppression and dictate the outcome of ICIs. OvCa harbors an abnormal TME, characterized by a desmoplastic extracellular matrix with high collagen levels. The accumulation of extracellular matrix components gives rise to increased compressive forces within the tumor, leading to blood vessel collapse and vessel perfusion reduction, causing impaired drug delivery and compromised trafficking of cytotoxic T-cells. The resulting TME is hypoxic and immunosuppressive. In our attempts to normalize the TME, we discovered that angiotensin II receptor 1 (AT1) is a key regulator of compressive solid stress. We showed in OvCa models that treatment with losartan – a widely prescribed anti-hypertensive drug – reduced matrix content and re-opened compressed vessels. As a result, blood perfusion increased, leading to enhanced drug delivery and improved chemotherapy efficacy. Furthermore, our retrospective analysis demonstrated that treatment with angiotensin blockers is associated with a 30-month overall survival benefit in OvCa patients. As a natural extension of this study, we are now asking the question: Can losartan reprogram the immunosuppressive TME of OvCa to enhance immunotherapy alone or with chemotherapy? Methods and Results: Here, using two syngeneic immunocompetent OvCa models and genetic and pharmacologic perturbations, we discovered that losartan – a widely prescribed anti-hypertensive drug – exhibits dual effects on both the TME and cancer cells to sensitize OvCa to chemo-immunotherapy. Specifically, losartan treatment i) reprograms the TME, leading to increased vascular perfusion, and thus enhances ICI drug delivery and immune effector cell intratumoral infiltration and function; and ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. Conclusions: Two of the greatest problems in ovarian cancer are chemotherapy resistance and the failure of immunotherapeutics to successfully alter the course of patients with OvCa. Our study offers a novel combination treatment strategy that can potentially enhance chemo-immunotherapy efficacy. As one of the most prescribed drugs for hypertension, the safety and low cost (less than $1-2/day) of losartan warrants rapid translation of our research to patients with OvCa. Citation Format: Yao Sun, Zhenzhen Yin, Limeng Wu, Changli Yue, Sonu Subudhi, Pinji Lei, Alona Muzikansky, Bo R. Rueda, Lei Xu. Losartan rewires ovarian cancer tumor-immune microenvironment and suppresses IGF-1 to amplify chemo-immunotherapy sensitivity [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A104.

Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs.

The prostacyclin (PGI2) receptor (IP) is a Gs-coupled receptor associated with blood pressure regulation, allergy, and inflammatory response. It is a main therapeutic target for pulmonary arterial hypertension (PAH) and several other diseases. Here we report cryo-electron microscopy (cryo-EM) structures of the human IP-Gs complex bound with two anti-PAH drugs, treprostinil and MRE-269 (active form of selexipag), at global resolutions of 2.56 and 2.41 angstrom, respectively. These structures revealed distinct features governing IP ligand binding, receptor activation, and G protein coupling. Moreover, comparison of the activated IP structures uncovered the mechanism and key residues that determine the superior selectivity of MRE-269 over treprostinil. Combined with molecular docking and functional studies, our structures provide insight into agonist selectivity, ligand recognition, receptor activation, and G protein coupling. Our results provide a structural template for further improving IP-targeting drugs to reduce off-target activation of prostanoid receptors and adverse effects.

Bosentan in the treatment of persistent pulmonary hypertension in newborns: a systematic review and meta-analysis.

Persistent pulmonary hypertension of the newborn is a life-threatening condition that affects about 1-2 per 1,000 live births worldwide. Bosentan is an oral dual endothelin receptor antagonist that may have a beneficial effect on persistent pulmonary hypertension of the newborn by reducing pulmonary vascular resistance and improving oxygenation. However, its role in persistent pulmonary hypertension of the newborn remains unclear. To systematically evaluate the efficacy and safety of bosentan as an adjuvant therapy for persistent pulmonary hypertension of the newborn in newborns. We searched six English and two Chinese databases from their inception to 1 January 2023 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomised controlled trials and retrospective studies that compared bosentan with placebo or other drugs for persistent pulmonary hypertension of the newborn in newborns. We performed a meta-analysis using random-effects models and assessed the risk of bias and heterogeneity in the included studies. We included 10 studies with a total of 550 participants. Bosentan significantly reduced the treatment failure rate (relative risk = 0.25, P < 0.001), pulmonary artery pressure (mean difference = -11.79, P < 0.001), and length of hospital stay (mean difference = -1.04, P = 0.003), and increased the partial pressure of oxygen (mean difference = 10.02, P < 0.001) and blood oxygen saturation (SpO2) (mean difference = 8.24, P < 0.001) compared with a placebo or other drugs. The occurrence of adverse reactions was not significantly different between bosentan and a placebo or other drugs. Bosentan is effective in the treatment of persistent pulmonary hypertension of the newborn but adverse reactions such as abnormal liver function should be observed when using it.

Spontaneous hemodynamic improvement after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension is observed within a short term after balloon pulmonary angioplasty.

Natural hemodynamic changesafter balloon pulmonary artery angioplasty (BPA) in a unified state without oxygen administration in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains undetermined. This study aimed to clarify the delayed changes in the hemodynamics after BPA in patients with CTEPH. We analyzed 73 consecutive patients with CTEPH who underwent BPA between July 2014 and December 2022. We extracted and evaluated hemodynamic data of the right heart catheter without oxygen administration immediately before and after the first BPA; and immediately before the second BPA, as the "post-delayed changes" after BPA. BPA significantly improved the mean pulmonary artery pressure (mPAP, mmHg) and pulmonary vascular resistance (PVR, dyn-s/cm5) from 36 (32-43) mmHg and 449 (312-627) dyn-s/cm5 before the first BPA to 28 (23-32) mmHg and 275 (217-366) dyn-s/cm5 immediately after BPA, and further significantly improved the values to 23 (20-28) mmHg and 225 (175-301) dyn-s/cm5 post-delayed changes after BPA, respectively. Improvement observed on account of delayed changes was observed both with and without pulmonary hypertension drugs. The delayed changes were observed during a period of 5-180days, which did not correlate with the changes in mPAP and PVR. Hemodynamic improvement owing to BPA was observed immediately after BPA; however, further improvement was observed as a result of delayed changes. mPAP improved by 3.4 ± 5.2mmHg and PVR by 53 (10-99) dyn-s/cm5 as delayed improvement. mPAP and PVR showed delayed improved by approximately 10% of their values before BPA.

Impacts of national volume-based drug procurement policy on the utilization and costs of antihypertensive drugs in a Chinese medicine hospital: an interrupted time series analysis of 5138 patients.

Objectives: The study aimed to estimate the effects of National Volume-based Drug Procurement (NVBP) policy on drug utilization and medical expenditures of hypertension patients in public medical institutions in mainland China. Methods: This study used patient-level data based on electronic health records retrieved from the hospital information system of Nanjing Hospital of Chinese Medicine. Data on patients with hypertension who received care at this institution between 2016 and 2021 was used for analysis. Segmented linear regression models incorporating Interrupted Time Series (ITS) analysis were adopted to examine the effects of NVBP policy on drug utilization and health expenditures of eligible patients. Drug utilization volume and health expenditures were the primary outcomes used to assess the policy effects, and were measured using the prescription proportion of each drug class and the overall per-encounter treatment costs. Results: After the implementation of NVBP policy, the volume of non-winning drugs decreased from 54.42% to 36.25% for outpatient care and from 35.62% to 15.65% for inpatient care. The ITS analysis showed that the volume of bid-winning drugs in outpatient and inpatient settings increased by 9.55% (p < 0.001) and 6.31% (p < 0.001), respectively. The volume changes in non-volume based purchased (non-VBP) drugs differed between outpatients and inpatients. The proportion of non-VBP drugs immediately increased by 5.34% (p = 0.002) overall, and showed an upward trend in the outpatient setting specially (p < 0.001) during the post-intervention period. However, no significant differences were observed in the proportion of non-VBP drugs in inpatient setting (p > 0.05) in term of level change (p > 0.05) or trend change (p > 0.05). The average per-visit expenditures of outpatients across all drug groups exhibited an upward trend (p < 0.05) post policy intervention. In addition, a similar increase in the overall costs for chemical drugs were observed in inpatient settings (coefficient = 2,599.54, p = 0.036), with no statistically significant differences in the regression slope and level (p = 0.814). Conclusion: The usage proportion of bid-winning drugs increased significantly post policy intervention, indicating greater use of bid-winning drugs and the corresponding substitution of non-winning hypertensive drugs. Drug expenditures for outpatients and health expenditures per visit for inpatients also exhibited an upward trend, suggesting the importance of enhanced drug use management in Traditional Chinese Medicine hospital settings.

Anti-inflammatory activity of benidipine hydrochloride in LPS-activated mammalian macrophages.

Benidipine hydrochloride (BH), a medication frequently used by the hypertension patients, acts as a calcium channel blocker. However, its effects on the macrophages have not been investigated thus far. Our goal was investigating the effect of the benidipine hydrochloride to modulate the J774.2 murine macrophage cells inflammatory activity. Our results suggest that in the absence of a standard stimulating agent (LPS) BH did not stimulate the macrophages to produce pro-inflammatory IL-12p40, TNF-α, GM-CSF and IL-6 cytokines. However, when BH was administrated to the cells in the presence of LPS as stimulating agent, it reduced the production of these pro-inflammatory cytokines. Therefore, it had anti-inflammatory activity. At the clinical setting this study suggests that BH can be utilized as hypertension drug that can suppress the inflammation associated with it.

Management of Hypertension in Patients With Polycystic Ovarian Syndrome: A Mini-Review.

Polycystic ovarian syndrome (PCOS) is a common problem among young women. It is characterized mainly by hyperandrogenism features, such as hirsutism, menstrual problems, and anovulation. Diagnosis is based on the existence of 2 items out of, oligo-ovulation, hyperandrogenism features, and ultrasounds findings. Cardiovascular complications such as hypertension are a prevalent serious condition in these patients which is mainly predisposed by the high levels of androgens, and insulin resistance. High blood pressure should be controlled well to prevent the progression of other serious conditions. Various antihypertensive drugs could be prescribed. However, in selecting an antihypertensive medication, other therapeutic properties of the drug should also be considered. Up to now, many clinicians do not differ between PCOS patients with hypertension and other hypertensive patients. However, being aware of the potential effects of each hypertension drug could help to choose better options for the patient. Here is a brief review of how each antihypertensive drug could affect PCOS women and if they cause any improvement in the disorder progression.

Brazilians’ perception regarding the use of generic drugs for hypertension and their equivalence relationship to reference drugs

Brazilians’ perception regarding the use of generic drugs for hypertension and their equivalence relationship to reference drugs

Association between Stress and Erectile Dysfunction among Adult Patients in a Tertiary Center in Nigeria

Erectile dysfunction (ED) is a complex disorder with a biopsychosocial etiology that causes chronic stress on the individual thereby worsening the outcome of the disorder. The aim of this study is to establish an association between stress level and erectile dysfunction among adult patients presenting in the general outpatient of our tertiary hospital. A cross sectional study involving 421 adult males selected by simple random sampling was conducted using the International Index of Erectile Dysfunction (IIEF-5) and the Modified Percieved Stress Scale (PSS-10) Among the respondents, 219(52%) had ED while a greater proportion of those who had ED had mild ED 109 (49.8%). The other factors associated with ED on bivariate analysis include tobacco use (p &lt; 0.05), alcohol intake (p &lt; 0.05), diabetes mellitus, hypertension, use of anti hypertensive drugs, use of oral hyperglycaemic drugs, and perceived stress levels. Logistic regression showed that age, tobacco use, alcohol intake, and perceived stress levels were independent predictors of ED among the respondents. Perceived stress level has been found to be associated with ED. Routine evaluation of sexual health and the perceived stress levels of men isrecommended, while stress management as part of management of ER is highly advocated.

Self-Reported Frequency of Adding Salt to Food and Risk of Incident Chronic Kidney Disease

The self-reported frequency of adding salt to foods could reflect a person's long-term salt taste preference, and salt intake has been associated with increased risk of cardiovascular diseases (CVD). Whether self-reported adding of salt to foods is associated with increased risk of chronic kidney disease (CKD) remains unknown. To prospectively examine the association of self-reported frequency of adding salt to foods with incident CKD risk in a general population of adults. This population-based cohort study evaluated UK Biobank participants aged 37 to 73 years who were free of CKD at baseline. Participants were enrolled from 2006 to 2010 and prospectively followed up for disease diagnosis. Data were analyzed from October 2022 to April 2023. Self-reported frequency of adding salt to foods, categorized into never or rarely, sometimes, usually, and always. Incident CKD cases were defined by diagnostic codes. Hazard ratios (HRs) and 95% CIs were calculated by using Cox proportional hazards models. Models were adjusted for several potential confounders including age, sex, race and ethnicity, Townsend Deprivation Index, estimated glomerular filtration rate (eGFR), body mass index, (BMI), smoking status, alcohol drinking status, regular physical activity, high cholesterol, diabetes, CVD, hypertension, infectious disease, immune disease, and nephrotoxic drugs use at baseline. Within a cohort of 465 288 individuals (mean [SD] age 56.32 [8.08] years; 255 102 female participants [54.83%]; 210 186 male participants [45.17%]), participants with higher self-reported frequency of adding salt to foods were more likely to have a higher BMI, higher Townsend Deprivation Index score, and diminished baseline eGFR compared with those who reported a lower frequency of adding salt to foods. Participants who added salt to their foods were also more likely than those who did not add salt to their foods to be current smokers and have diabetes or CVD at baseline. During a median (IQR) follow-up of 11.8 (1.4) years, 22 031 incident events of CKD were documented. Higher self-reported frequency of adding salt to foods was significantly associated with a higher CKD risk after adjustment for covariates. Compared with those who reported never or rarely adding salt to foods, those who reported sometimes adding salt to food (adjusted HR [aHR], 1.04; 95% CI, 1.00-1.07), those who reported usually adding salt to food (aHR, 1.07; 95% CI, 1.02-1.11), and those who reported always adding salt to food (aHR, 1.11; 95% CI, 1.05-1.18) had an increased risk of CKD (P for trend < .001). In addition, eGFR, BMI, and physical activity significantly modified the associations, which were more pronounced among participants with a higher eGFR, lower BMI, or lower level of physical activity. In this cohort study of 465 288 individuals, a higher self-reported frequency of adding salt to foods was associated with a higher risk of CKD in the general population. These findings suggest that reducing the frequency of adding salt to foods at the table might be a valuable strategy to lower CKD risk in the general population.

Chronic thromboembolic pulmonary hypertension: clinical case and problem review

In this article there was presented a clinical case of the chronic thromboembolic pulmonary hypertension (CTEPH) in the patient with small arteries damage. The thromb visualization was done by the lung perfusion multispiral computer tomography. The general positions of the definition, the diagnosis and treatment of the CTEPH were elucidated too. It was stated the CTEPH is a potential curable disease in case of the surgery in time. But there are some situations when it is not possible to provide the surgery and, in this case, the CTEPH treatment by specific pulmonary hypertension drugs could be used

EFFECTIVENESS PROFILE OF AMLODIPINE AND LISINOPRIL IN HYPERTENSION OUTPATIENTS AT PRATAMA CLINIC SIDOARJO

Hypertension is the leading cause of premature death worldwide. An estimated 1.28 billion  adults aged 30-79 years worldwide have hypertension. Treatment of hypertension is usually aimed at preventing morbidity and mortality from hypertension. The choice of drugs for each patient's hypertension depends on the metabolic and subjective side effects caused. This study aims to determine the effectiveness profile of antihypertensive drugs amlodipine 10 mg or lisinopril 10 mg in outpatients at the Sidoarjo Pratama Clinic for January- March 2023. This research method is observational, with a cross-sectional approach and data collection. Quantitative analysis was then done using the statistical program SPSS 24 with univariate analysis. The results of the independent t-test showed a significance value for the systolic category of 0.780 &gt; 0.05 and a significance value for the diastolic category of 0.931 &gt; 0.05. Patients receiving therapy with amlodipine 10 mg or lisinopril 10 mg reached the target in 30 patients. After doing the independent t-test before and after therapy in both the systolic category and the diastolic category, it can be concluded that there is no significant difference in the effectiveness of the two groups. Keywords: Amlodipine, Blood Pressure, Hypertension, Lisinopril

Identification of Native Root Nodulating Bacteria from Mucuna (Mucuna pruriens L.)

Background: Mucuna (Mucuna pruriens L.) is an annual herbaceous climber, grown as a medicinal, green manure, cover and smothering crop. The mucuna seeds contains L-DOPA (L-3, 4 dihydroxy phenylalanine), a non-protein amino acid, extensively used for Parkinson and hypertensive drug. Injudicious application of nitrogenous fertilizers leads to deterioration of soil quality which results into loss of crop yield and quality. The application of microbial inoculant containing efficient native rhizobia enhances the nodular properties, N2-fixation and soil quality. Therefore, Rhizobium strain associated with mucuna was isolated, biochemically characterized and identified. The 16SrRNA sequencing revealed that Sinnorhizobium mililoti, a gram negative symbiotic nitrogen fixing bacteria is present in root nodules of mucuna. Methods: Root nodules were extracted from mucuna grown at ICAR- Krishi Vigyan Kendra, Doddaballapura Taluk, Bengaluru Rural District, Karnataka, then cultured, screened and characterized in the laboratory. The 16SrRNA sequencing and phylogenetic analysis was done to identify the native rhizobial strain. Result: Identification of native root nodulating bacteria through 16SrRNA sequencing concluded that Sinnorhizobium mililoti strain associated with the root nodules of Mucuna (Mucuna pruriens L.).

Relationship between blood culture time to positivity, mortality rate, and severity of bacteremia

ObjectivesWe investigated the association between patient severity or mortality and time to positivity in bacteremia caused by various pathogens. Patients and methodsThis single-center retrospective study included patients with positive blood culture results. ResultsLonger time to positivity was associated with 30-day mortality for Staphylococcus aureus (221 cases, time to positivity: 17.4 h in the 30-day mortality group vs. 14.1 h in the survival group). Age, chronic kidney disease, cerebrovascular disease, hypertensive drug use, consciousness disorder, and minimal systolic blood pressure were significant predictors of 30-day mortality. For S. aureus, mortality within 30 days was significantly higher when time to positivity was > 24 h (p = 0.04). The time to positivity of Streptococcus pneumoniae, α, β-hemolytic Streptococcus, Enterococcus sp., Enterobacteriaceae, glucose-nonfermenting Gram-negative rods, Candida sp., and anaerobe was not significantly associated with 30-day mortality. ConclusionsAmong various pathogens, time to positivity > 24 h was associated with 30-day mortality for S. aureus.

235. Investigation of the relationship between the number of positive blood cultures and patient prognosis

Abstract Background The relationship between the number of positive blood cultures (NPBCs) and clinical outcomes has not been well-studied. The purpose of this study was to assess the impact of NPBCs (one set or two) on clinical outcomes. Methods We conducted a retrospective study comparing the clinical features of two sets of positive blood cultures (NPBCs=2) and one set of positive blood culture (NPBCs=1) in adult patients with bacteremia and fungemia from 2004 to 2021 at a tertiary hospital in Tokyo, Japan. We focused on four pathogens commonly encountered in clinical practice, including Staphylococcus aureus (S. aureus), Streptococci, gram-negative rods (GNR) (Enterobacterales and Pseudomonas aeruginosa), and Candida species, as the true causative pathogens in bacteremia and fungemia. The primary outcome was in-hospital mortality, and secondary outcomes were ICU admission and use of vasopressor drugs. Results In univariate analysis, NPBCs=2 for S. aureus was associated with vasopressor use, and NPBCs=2 for Streptococci was linked to a higher rate of ICU admission. However, these differences were not significant in multivariate analysis. Interestingly, NPBCs=2 for S. aureus had a positive impact on in-hospital mortality compared with NPBCs=1 (OR 0.574, 95%CI 0.376–0.877, p &amp;lt; 0.05). NPBCs for Candida species did not affect clinical outcomes. Furthermore, NPBCs=2 for GNR was associated with vasopressor use (OR 1.62, 95%CI 1.27–2.07, p &amp;lt; 0.05) in both univariate and multivariate analysis. We performed logistic regression analysis using the five items with the highest clinical significance: NPBCs=2, serum Cr &amp;gt; 1.2 mg/dL, Hb &amp;lt; 12 g/dL, heart rate &amp;gt; 90 beats/min, and platelet count &amp;lt; 150,000/μL. Based on the β coefficient, we assigned scores to each item and created a STAT-2 (S: Serum Cr, T: Thrombocytopenia, A: Anemia, T: Tachycardia, 2: NPBCs=2) score for the use of hypertensive drugs for GNR. The receiver operating characteristic (ROC) curve for the STAT-2 score with a cutoff of 6 points or higher had an area under the curve (AUC) of 0.763. The specificity was 90.8%, with a positive likelihood ratio of 4.13 (95% CI 3.40-5.02). Conclusion Our study suggests that NPBCs can predict clinical outcomes in patients with certain pathogenic infections. Disclosures All Authors: No reported disclosures

Active Compounds of Sembung Leaves (Blumea balsamifera DC) in Silico Screening as Antihypertensives

Hypertension is a structural or functional change in the arteries or the organs it supplies caused by increased blood pressure. Angiotensin-converting enzyme (ACE) can increase blood pressure by converting inactive angiotensin I to active (angiotensin II). Captopril is a hypertension drug that can inhibit ACE activity. Sembung leaf (Blumea balsamifera DC) is a plant that can potentially have antihypertensive activity. This study aims to identify the interaction of active compounds in sembung leaves against ACE as antihypertensive drug candidates through an in silico test based on pharmacodynamic and pharmacokinetic parameters using two docking software, Autodock Vina and PyRx. The results showed that Luteolin was the best test ligand besides having lower ΔG and Ki than control ligands and higher Kd than control ligands.  Luteolin was identified to interact with Zn and hydrogen bond interactions at the active site and met the criteria in Lipinski analysis, ADME, and toxicity, so this compound is relatively safe to be used as a drug candidate for the treatment of hypertension.

An Investigation of the Risk Factors of Osteoporosis and the Correlation between Drug Consumption and Osteoporosis: Results of the Fasa PERSIAN Cohort Stud

Background: Osteoporosis, as the most common bone-related disease, causes massive irrecoverable consequences for the health level and life quality of people, especially at advanced ages. The present research aimed to evaluate the prevalence and risk factors of osteoporosis and the correlation between drug consumption and osteoporosis. The present study is a cross-sectional study and is the first stage in the longitudinal Fasa branch of the PERSIAN cohort study. Materials and Methods: The subjects of the present cross-sectional-descriptive study consisted of all cohort populations of Fasa University of Medical Sciences (n=10123) who were chosen through census sampling. The data were collected through a demographic data form and medication checklist, and SPSS-22 was used to analyze the data. Results: Among a total population of 10133, 994 had osteoporosis, of which 880 were women and 114 were men, which was statistically significant (P&lt;0.05). The overall prevalence rate of osteoporosis was estimated to be 9.8%, and the mean age of people with osteoporosis was 56 years. The results demonstrated significant positive correlations among osteoporosis and age, gender, marital status, education, smoking, physical activity, alcohol use, hypertension, diabetes mellitus, fatty liver, and glucocorticoid steroid drugs (P&lt;0.05). Conclusion: Identifying factors related to osteoporosis can be effective in adopting health promotion programs at all healthcare and prevention levels. Thus, the use of some drugs, such as corticosteroids, as an alarm and risk factor should be taken into consideration by specialists when adopting healthcare plans.

"Integrated BORDA-TOPSIS for Hypertension Drugs Ranking and Treatment"

"Integrated BORDA-TOPSIS for Hypertension Drugs Ranking and Treatment"

Mendelian randomization study of the relevance of blood pressure to vascular mortality among 150,000 participants in the mexico city prospective study

Abstract Background Mendelian randomization (MR) studies are commonly used to reduce confounding and reverse-causality when estimating the effects of risk factors on disease and provide estimates of effects over the whole life-course. However, most previous MR studies have been conducted in populations of European-ancestry. We used MR to investigate the effect of systolic blood pressure (SBP) on vascular mortality at ages 35-74 in a large prospective study of Mexican adults. Methods Between 1998 and 2004, 150,000 adults aged ≥35 years were recruited into the Mexico City Prospective Study and followed for median 19 years(1,2). Using 886 externally-selected single nucleotide polymorphisms (SNPs)(3) we created a genetic risk score for SBP (GRS-SBP). Those taking an antihypertensive drug at recruitment had their SBP adjusted by +6 mmHg(2) (adjustment by +15 mmHg rather than +6 mmHg was done in a sensitivity analysis). Cox regression and the MR ‘ratio’ method were then used to estimate the causal effect of SBP on vascular mortality at ages 35-74 years. Analyses were adjusted for age at risk, sex, residential district, education, smoking, alcohol consumption, physical activity, adiposity, diabetes mellitus and the first 7 genetic principal components. They excluded those aged ≥75 years, had incomplete data, or had prior vascular disease or any other chronic condition (except diabetes). Alternative MR approaches (inverse-variance-weighted, weighted median and MR Egger) were used for sensitivity analyses. Conventional epidemiological analyses of the association between SBP and mortality after correction for regression dilution bias were also done. Results Among 127,849 included individuals, the GRS-SBP explained 1.9% of baseline SBP variation. Those in the top fifth of the GRS-SBP distribution had 6.6 mmHg higher SBP and twice the prevalence of self-reported hypertension and antihypertensive drug use than those in the bottom fifth, but the GRS-SBP was uncorrelated with other factors. The strength of association between GRS-SBP and measured SBP was broadly similar in men and women, at different ages, and between people with different proportions of Amerindian genetic ancestry. Using the ratio method and a single estimate of the association of GRS-SBP with SBP, each 10 mmHg higher genetically predicted SBP was associated with 58% higher vascular mortality at ages 35-74 years (RR 1.58, 95% CI 1.27-1.96), including 69% higher ischaemic heart disease mortality (RR 1.69, 95% CI 1.31-2.16) and 65% higher stroke mortality (RR 1.65, 1.15-2.33). These genetic estimates were somewhat larger than conventional observational associations of usual SBP to risk. Alternative MR approaches found no evidence of pleiotropy and yielded similar conclusions. Conclusions These MR analyses confirm that blood pressure is a major cause of premature death from vascular diseases in Mexican adults.