The Association Between Systemic Arterial Hypertension and Chronic Obstructive Pulmonary Disease. Results from the U.S. National Health and Nutrition Examination Survey 1999-2018: A Cross-sectional Study.

Background: Systemic arterial hypertension (HTN) is one of the common comorbidities among patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association between HTN and COPD. Methods: A total of 46,804 eligible non-pregnant participants aged ≥ 20 years examined in the Mobile Examination Center of the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this cross-sectional study. Participants with invalid data on covariates, HTN, and COPD were excluded. The association between HTN and COPD was studied using logistic regression upon adjusting the potential covariates. Results: Among the participants, 46.1% (95% confidence interval [CI], 45.3-46.9) had HTN, and 6.8% (95% CI, 6.4-7.2) had self-reported COPD. COPD was associated with HTN (OR [odds ratio]=1.18, 95% CI [1.05-1.31], P<0.01) after adjusting for demographics, socioeconomic factors, smoking, diabetes, body mass index, and medication use, including inhaled corticosteroids and methylxanthines. The association between HTN and COPD was significant among adults younger than 60 years (P<0.01). Stratified by smoking status, there was a significant association between HTN and COPD in current heavy smokers (1.25, 95% CI [1.01-1.58]; P=0.04). Conclusions: In this nationwide survey, COPD was associated with HTN. The association was more robust among adults younger than 60 years and current heavy smokers. Future prospective studies are needed to examine the relationship between HTN and COPD.

Ultrasensitive detection of blood biomarkers of Alzheimer's and Parkinson's diseases: a systematic review.

Purpose: Neurodegenerative disorders are a global health burden with costly and invasive diagnoses relying on brain imaging technology or CSF-based biomarkers. Therefore, considerable efforts to identify blood-biomarkers for Alzheimer's (AD) and Parkinson's diseases (PD) are ongoing. Objectives: This review evaluates the blood biomarkers for AD and PD for their diagnostic value. Methods: This study systematically reviewed articles published between July 1984 and February 2021. Among 1266 papers, we selected 42 studies for a systematic review and 23 studies for meta-analysis. Results & conclusion: Our analysis highlights P-tau181, T-tau and Nfl as promising blood biomarkers for AD diagnosis. Nfl levels were consistently raised in 16 AD and three PD cohorts. P-tau181 and T-tau were also significantly increased in 12 and eight AD cohorts, respectively.

Pharmacokinetics and safety of liposomal bupivacaine after local infiltration in healthy Chinese adults: a phase 1 study.

BACKGROUND: Liposomal bupivacaine (LB) is a long-acting formulation of bupivacaine. The safety and efficacy of LB has been demonstrated across surgical procedures. However, pharmacokinetic (PK) parameters and safety of LB in the Chinese population have not been assessed. METHODS: In this single-arm, single center, phase 1, open-label study, PK and safety of local infiltration with LB 266 mg were assessed in healthy Chinese adults. Eligible participants were aged 18 to 55 years with biologic parents and grandparents of Chinese ethnicity, in generally good health (i.e., no clinically significant abnormalities), and with a body mass index (BMI) 19.0 to 24.0 kg/m2 (inclusive) and body weight ≥ 50 kg. RESULTS: Participants (N = 20) were predominantly men (80 %); mean age was 32 years; and mean BMI was 21.8 kg/m2. After LB administration, mean plasma levels of bupivacaine rapidly increased during the first hour and continued to increase through 24 h; plasma levels then gradually decreased through 108 h followed by a monoexponential decrease through 312 h. Geometric mean maximum plasma concentration was 170.9 ng/mL; the highest plasma bupivacaine concentration detected in any participant was 374.0 ng/mL. Twenty-two treatment-emergent adverse events were reported (mild, n = 21; moderate, n = 1). CONCLUSIONS: After single-dose administration of LB, PK measures were similar to a previously reported profile in US adults. The highest observed peak plasma concentration of bupivacaine was several-fold below the plasma concentration threshold accepted as being associated with neurotoxicity or cardiotoxicity (2000-4000 ng/mL). These data support that LB is well tolerated and safe in individuals of Chinese descent. TRIAL REGISTRATION: NCT04158102 (ClinicalTrials.gov identifier), Date of registration: November 5, 2019.

Null association between serum 25-hydroxyvitamin D levels with allergic rhinitis, allergic sensitization and non-allergic rhinitis: A Mendelian randomization study.

BACKGROUND: Previous observational studies have not found a conclusive association between serum 25-hydroxyvitamin D (25(OH)D) levels and allergic rhinitis (AR) or allergic sensitization (AS). OBJECTIVE: To investigate a causal association between 25(OH)D levels with risk of AR and AS, using a two-sample Mendelian randomization (MR) approach. METHODS: Seven single nucleotide polymorphisms (SNPs), previously shown to be associated with serum 25(OH)D levels, were identified as instrumental variables. The primary outcome was AR, and the secondary outcomes were AS and non-allergic rhinitis (NAR). The genome-wide association (GWA) summary statistics of the outcomes were obtained from two cohort studies (EAGLE Consortium and UK Biobank). An MR analysis with random-effects inverse-variance weighted method was performed as the primary analysis to estimate overall effect size (odds ratio [OR] and 95% confidence interval [CI]). Sensitivity analysis using weighted median method and MR-Egger regression method was conducted. A subgroup analysis based on 25(OH)D synthesis-related SNPs was further applied. RESULTS: Serum 25(OH)D levels were not causally associated with risk of AR (OR: 0.960; 95% CI: 0.779-1.184), AS (OR: 1.059; 95% CI: 0.686 to 1.634) or NAR (OR: 0.937; 95% CI: 0.588-1.491). Subgroup analysis also showed null association between 25(OH)D synthesis-related SNPs and the outcomes. Sensitivity analyses yielded similar results. CONCLUSIONS AND CLINICAL RELEVANCE: This MR study found no evidence supporting a causal association between serum 25(OH)D levels and risk of AR, AS and NAR in European-ancestry population. This argues against the previous postulation that vitamin D supplementation is effective in prevention of allergic diseases.

25-Hydroxyvitamin D and the risk of incident diabetes in Hong Kong Chinese.

OBJECTIVE: To investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and risk of incident diabetes in Hong Kong Chinese, after accounting for the effect of multiple bone- and mineral-related markers. DESIGN: We conducted a retrospective study on the Hong Kong Osteoporosis Study cohort. Incident diabetes was ascertained using electronic medical records. Serum 25(OH)D was measured at baseline and its association with incident diabetes was evaluated using multivariable Cox proportional-hazard regression. PARTICIPANTS: Individuals (n 4342) aged 20 years or above (1395 men, 2947 women; mean age 54·3 (sd 16·5) years) from the Hong Kong Osteoporosis Study, who were free of diabetes at baseline, were included. RESULTS: During 40 124·7 person-years of follow-up (a median of 9·2 years), 443 participants developed diabetes. Mean 25(OH)D was 63·34 (sd 13·07) nmol/l. Age-, sex- and BMI-adjusted Cox proportional-hazard regression showed no significant difference in the risk of incident diabetes between the lowest and the highest quintiles of 25(OH)D. In the analysis of the interaction effect between 25(OH)D and serum Ca, the interaction term did not affect the risk of incident diabetes significantly (P = 0·694). Similarly, there was no significant interaction of different subgroups (age, sex, BMI, femoral-neck T-score, serum Ca levels) with serum 25(OH)D. CONCLUSIONS: The present study finds that serum vitamin D level is not associated with the risk of incident diabetes in Hong Kong Chinese and this relationship is not modified by serum Ca level.

Optimal vitamin D status and its relationship with bone and mineral metabolism in Hong Kong Chinese.

BACKGROUND: Although 25-hydroxyvitamin D (25[OH]D) is commonly used to define vitamin D status, there is no consensus on the cutoff levels for vitamin D deficiency and insufficiency. In this study, we aimed to identify the 25(OH)D threshold that maximally suppressed parathyroid hormone (PTH) in Hong Kong Chinese population. METHODS: The study included 5276 participants (70% female) of the Hong Kong Osteoporosis Study aged 20 or above who had total 25(OH)D measured. Three-phase segmented regression was used to identify the optimal break-point between 25(OH)D and PTH. RESULTS: The prevalence of vitamin D deficiency observed was 43.8% and the prevalence of insufficient (<75nmol/L) or deficient (<50nmol/L) vitamin D levels was 90.1% in our study population. Using unadjusted three-phase segmented regression, the estimated first and second break-point of 25(OH)D on PTH suppression were 32nmol/L (95% CI: 29-35) and 89nmol/L (95% CI: 77-101) with an r2 of 0.048, whereas the estimated first and second break-point of 25(OH)D were 27nmol/L (95% CI: 24-30) and 47nmol/L (95% CI: 37-56) after adjusting for factors affecting bone and mineral metabolism. In addition, the relationship between 25(OH)D and PTH significantly differed by sex and age. CONCLUSION: The threshold for 25OHD at the point of maximal suppression of PTH estimated in this study was lower than the suggested threshold of vitamin D deficiency in the literature, perhaps due to race or assay differences, and the relationship between vitamin D and PTH changed with sex and age. Standardization in the methodology of searching for the optimal break-point is desirable so that a consensus on cutoff points can be obtained.

Rise and fall of anti-obesity drugs.

Although it is not generally a life-threatening disease, obesity is becoming a major health problem worldwide. It can be controlled by means of drugs, and, consequently, these are required to be safe as well as effective. In this paper, we summarize the fate of various drugs that have been introduced for clinical use in the treatment of obesity. Fenfluramine and dexfenfluramine were withdrawn because of heart valve damage. Sibutramine suppresses appetite and increases heart rate and blood pressure. In the Sibutramine Cardiovascular OUTcomes trial, an increase in major adverse cardiovascular events prompted its withdrawal in Europe and the United States. Rimonabant is an endocannabinoid receptor antagonist that reduces body weight and ameliorates some cardiovascular risk factors. However, adverse psychiatric side effects led to its withdrawal as well. Orlistat is approved in Europe and the United States for the treatment of obesity, but its use is limited by gastrointestinal side-effects. Ephedrine and caffeine are natural ingredients in foods and supplements that may help the person to lose weight. In the light of several failed attempts, there is a clear need to develop drugs that are effective and safe in the long term in order to successfully combat the phenomenon of obesity .

A new paradigm for managing dyslipidemia with combination therapy: laropiprant + niacin + simvastatin.

IMPORTANCE OF THE FIELD: Despite effective lowering of low-density lipoprotein cholesterol (LDL-C) with statin for prevention of cardiovascular adverse events, residual risk remains high due to low high-density lipoprotein cholesterol (HDL-C) levels in patients with mixed dyslipidemia. As a result, alternative treatment options to raise HDL-C are being investigated intensively. Currently, niacin is the most potent lipid lowering agent for raising HDL-C levels together with lowering of triglyceride and LDL-C. Previous clinical studies have demonstrated that niacin therapy significantly reduces the risk of cardiovascular events in high risk subjects. However, the clinical use of niacin is limited by its major adverse effect, cutaneous flushing. Although the use of extended-release (ER) formulation can reduce flushing, the tolerability and compliance of niacin remains suboptimal. A selective antagonist of prostaglandin D Type 1 receptor, laropiprant, has been investigated in a number of clinical studies and shown to be effective in reducing niacin-induced flushing. Despite the potential of laropiprant in reducing niacin-induced flushing, the long-term clinical efficacy and potential off-target side effects are not well studied. AREAS COVERED IN THIS REVIEWS: In this article, the pharmacological properties, clinical efficacy and future perspective of this combination therapy of simvastatin/ER niacin/laropiprant are reviewed. WHAT THE READER WILL GAIN: Readers will understand both the mechanism and clinical effects of the combination therapy of simvastatin/ER niacin/laropiprant. TAKE HOME MESSAGE: The triple combination therapy of simvastatin/ER niacin/laropiprant may reduce flushing side effects and facilitate a more comprehensive treatment for patients with mixed dyslipidemia.

Raising highly desirable lipoprotein versus lowering deleterious lipoprotein.

Evaluation of: Taylor AJ, Villines TC, Stanek EJ et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N. Engl. J. Med. 361(22), 2113-2122 (2009). Epidemiological evidence suggests that elevated low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) are both factors causing coronary heart disease. These authors compared extended-release niacin, which raises HDL-C, with ezetimibe, which lowers LDL-C, in a study named Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies (ARBITER 6-HALTS). The study was terminated early and only 208 patients were included in the analysis. Ezetimibe decreased LDL-C by 19.2%, to 66 mg/dl (1.7 mmol/l), whereas niacin increased HDL-C by 18.4%. Ezetimibe did not reduce carotid intima-media thickness, whereas niacin decreased it significantly. Moreover, major adverse cardiovascular events occurred in 5% of the ezetimibe group but only 1% of the niacin group (p = 0.04). The study suggests that niacin may be more effective than ezetimibe as an adjunct to statin in regressing atherosclerosis and in preventing cardiovascular events. This small study of short duration reported a very large treatment effect, so the findings need to be confirmed in a larger longer trial. Nevertheless, it provides the evidence that we now have an additional class of drugs besides statins that can reduce atherosclerosis and cardiovascular events.

Behind the rosiglitazone controversy.

On 23 September 2010, the US FDA and the EMA issued statements announcing their response to data implicating the use of the antidiabetes drug rosiglitazone (Avandia(®), GlaxoSmithKline plc, London, UK) with an increased risk of cardiovascular events, including acute myocardial infarction and stroke. The EMA has implemented an immediate suspension of the drug, meaning that it will no longer be available in Europe. The FDA stopped short of a total suspension, but has stated that use of the drug should be restricted to patients with Type 2 diabetes who cannot control their diabetes with other medications. In this article, Bernard Cheung of the Expert Review of Clinical Pharmacology Editorial Advisory Board gives his insight into the matter. Cheung graduated from the University of Cambridge (UK) and received a PhD in Clinical Pharmacology in 1995. He then joined the University of Hong Kong as the Lecturer in Clinical Pharmacology and later became Professor. He held the Chair in Clinical Pharmacology and Therapeutics at the University of Birmingham (UK) in 2007-2009. Cheung's main research interest is in cardiovascular diseases and risk factors, including hypertension and the metabolic syndrome. He works on vasoactive peptides, such as adrenomedullin and urotensin II. He is also interested in clinical trials, meta-analyses, drug utilization and medication safety and is the Chief Editor of the Open Diabetes Journal, and an Executive Editor of the British Journal of Clinical Pharmacology.

Prolonged seated immobility-associated venous coagulability in a factor V Leiden heterozygote: a case-comparative study.

Prolonged sitting and thrombophilia may compound the risk of venous thromboembolism. In order to investigate suspected local lower limb venous procoagulant changes associated with prolonged sitting-induced venous stasis in a man heterozygous for factor V Leiden (participant X), we qualitatively compared venous coagulability in lower and upper limb plasma in this participant and three other male Caucasians over 8 h of sitting. Of the four participants, participant X had the highest baseline values of prothrombin fragments 1 and 2, thrombin-antithrombin III complexes, tissue plasminogen activator, plasminogen activator inhibitor 1, D-dimer and soluble thrombomodulin. Over time, in participant X, venous prothrombin fragments 1 and 2, thrombin-antithrombin III complexes, and soluble thrombomodulin decreased in both limbs; D-dimer decreased in the lower limbs but increased in the upper limbs; the tissue plasminogen activator/plasminogen activator inhibitor 1 molar ratio increased in both limbs; and minimal changes were noted in haematocrit. A foot volume increase was associated with vague symptoms towards the end of the study. Overall, these changes were similar to those observed in other participants. It is concluded from this case comparison that prolonged sitting of 8 h duration under normal atmospheric conditions did not result in local, as well as systemic, procoagulant haemostatic responses in a heterozygote for factor V Leiden when compared with other healthy volunteers. However, this observed, possibly adaptive, response is more likely to be compromised in factor V Leiden subjects during continued or increased venous endothelial stress or in the presence of other venous thromboembolism risk factors.

The relationship between hypertension and anxiety or depression in Hong Kong Chinese.

BACKGROUND: Psychosocial stress can be the cause or the consequence of hypertension. OBJECTIVE: To study the association between hypertension and anxiety or depression in adults from Hong Kong, China. SUBJECTS AND METHODS: Patients with diagnosed hypertension (n=197) were recruited to complete the Hospital Anxiety and Depression Scale (HADS) questionnaire. The control group comprised 182 normotensive subjects recruited using random telephone numbers. RESULTS: The score in the anxiety subscale (HADS-A) of the HADS correlated with age (r= -0.23, P<0.001) and sex (r=0.11, P=0.042), and was found to be higher in women. The score in the depression subscale (HADS-D) correlated with age (r=0.17, P=0.003) and hypertension (r=0.12, P=0.039), but not with sex (r=0.02, P=0.68). When the control subjects were matched for sex and age with the subjects with hypertension, the mean HADS-A score was 5.51+/-0.41 in 113 hypertensive subjects and 4.38+/-0.39 in 113 normotensive subjects (P=0.047). The mean HADS-D score was 5.56+/-0.39 in the hypertensive and 4.76+/-0.32 in the normotensive subjects (P=0.11). Multiple regression analysis using data from both groups indicated that the HADS-A score was related to the HADS-D score (beta=0.49, P<0.001), age (beta= -0.25, P<0.001) and sex (beta=0.12, P=0.01) (R(2)=0.28), whereas the HADS-D score was related to the HADS-A score (beta=0.48, P<0.001), age (beta=0.30, P<0.001), positive smoking status (beta=0.13, P=0.004) and lack of exercise habit (beta=0.12, P=0.008) (R(2)=0.31). Hypertension was related to waist circumference, history of parental hypertension and age (R(2)=0.38, P<0.001). Anxiety and depression scores were rejected as independent variables. CONCLUSIONS: Hypertension was associated with anxiety but not depression; however, age, history of parental hypertension and central obesity appeared to have a stronger association with hypertension in adults from Hong Kong.