scholarly journals Higher Triglyceride and Normal HDL-C Concentrations, the Triglyceride/HDL-C Concentration Ratios ≥ 3.5, and Insulin Resistance as Potential Predictors of Developing Higher Paroxetine Concentrations and Suicide in the Early Months of Medication

Author(s):  
Eiko K. Nakagawa

Background: There are several reported results. Hazard ratios for suicide tended to increase with dose for selective serotonin reuptake inhibitors (SSRIs). The suicide rate in the first three months following initiation of paroxetine exposure was 799 per 100,000 person-years, while, annual suicide rates for depression and anxiety were 81.8 and 76.7, respectively. SSRIs serum concentrations were significantly associated with increases of triglyceride (TG) levels. SSRIs inhibited insulin signaling and beta cell function by a dose-dependent manner.Objective: Based on symptoms and blood lipid levels indicated by a young patient who committed suicide, my objective is to propose that higher TG concentrations above the normal range, normal high-density lipoprotein cholesterol (HDL-C) concentrations, and the TG/HDL-C concentration (mg/dL) ratios ≥ 3.5 to estimate insulin resistance are potentially useful in identifying individuals who are developing higher paroxetine concentrations.Methods: The glucose and lipid levels in the blood examination which was performed in an emergency hospital to where the patient was delivered by ambulance after his abnormal behaviors on the 14th day after the start of paroxetine treatment, were used for calculation and examination. Fasting TG levels were estimated by calculating TG values (TG-Cal) using the measured value of TG and a formula reported by Hitze et al., or the measured values of total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C), and nine formulas referred and reported by Dansethakul et al. Paroxetine levels in the patient’s serum were estimated by calculation using the regression coefficient of TG 46.49 mg/dL, with which the paroxetine serum concentration 75 ng/mL was associated in the results reported by Fjukstad et al.   Results: The 20-year-old patient free of recent suicidal ideation developed intense violent suicidal preoccupation, and exhibited abnormal behaviors in the first 41 days after the start of paroxetine treatment 10 mg twice daily. He sent emails with advanced notice of suicide to his friend on the 7th, 17th, and 18th days, drank alcohol alone and exhibited abnormal behaviors in a market place around noon, blacked out, and was ambulanced to the emergency hospital on the 14th day. Finally, he carried out suicide on the 41st day after three days of abrupt discontinuation of paroxetine. He never exhibited these abnormal behaviors before paroxetine exposure. The levels of glucose, TG, TC, HDL-C, and LDL-C measured in the blood examination at 15:56 on the 14th day after the start of paroxetine treatment were 111, 498, 185, 53, and 92 mg/dL, respectively. The levels of TC, HDL-C, and LDL-C were in the normal ranges, respectively, probably suggesting metabolic normality of the patient before paroxetine exposure. In order to estimate the fasting TG level, TG-Cal values were calculated to be 278, 200, 258, 240, 268, 272, 310, 308, 311, and 250 mg/dL in the range of 200 – 311 mg/dL beyond the normal range of TG 50 – 150 mg/dL. TG-Cal/HDL-C ratios were also calculated to be in the range of 3.8 – 5.9 (200/53 – 311/53), probably suggesting that the patient was in the stage of insulin resistance development. The paroxetine level in the patient’s serum was estimated to be in the range of 161 – 387 ng/mL by calculation using formulas 75(TG-Cal – 71)/46.49, 75(TG-Cal – 92.25)/46.49, and 75(TG-Cal – 100)/46.49, on the assumption that the patient’s TG levels before paroxetine exposure were 71, 92.25, and 100 mg/dL, respectively. The paroxetine concentrations in the range of 161 – 387 ng/mL were much higher than the therapeutic reference range 30 – 120 ng/mL.    Conclusions: The above results probably suggest that paroxetine exposure, higher TG concentration, higher paroxetine concentration, and suicide coincided in the patient. Follow-up measurements of TG and HDL-C concentrations and the TG/HDL-C ratios have a potential to predict and prevent suicides in the early months of paroxetine exposure. 

2021 ◽  
Vol 10 (5) ◽  
pp. 904
Author(s):  
Jun Watanabe ◽  
Masato Hamasaki ◽  
Kazuhiko Kotani

Introduction: Helicobacter pylori (H. pylori) infection is positively associated with cardiovascular diseases, but the involvement of lipids in this association remains unclear. The present study reviewed the changes in circulating lipid levels following H. pylori eradication. Methods: A PubMed database was searched until December 2020 to identify randomized control trials (RCTs) and non-RCTs investigating the effect of H. pylori eradication on the lipid levels in inverse variance-weighted, random-effects meta-analyses. Results: A total of 24 studies (four RCTs and 20 non-RCTs) with 5270 participants were identified. The post-eradication levels were increased for high-density lipoprotein cholesterol (HDL-C; mean difference (MD) 2.28 mg/dL, 95% confidence interval (CI) 1.90 to 2.66) and triglyceride (TG; MD 3.22 mg/dL, 95% CI 1.13 to 5.31) compared with the pre-eradication levels. H. pylori eradication resulted in little to no difference in the low-density lipoprotein-cholesterol levels (MD −2.33 mg/dL, 95% CI −4.92 to 0.26). In the analyses of RCTs only, the findings for elevated HDL-C levels, but not TG, were robust. Conclusions: H. pylori eradication increases the HDL-C levels. Further studies are needed to elucidate the effects of lipid changes following H. pylori eradication on cardiovascular diseases.


Author(s):  
Hsiao-Han Chao ◽  
Yi-Hung Liao ◽  
Chun-Chung Chou

Background: Aging and chronic degeneration are the primary threats to cardiometabolic health in elderly populations. Regular appropriate exercise would benefit the advanced aging population. Purpose: This study investigates whether the degree of weekly tennis participation exhibits differences in primary cardiometabolic parameters, including arterial stiffness, inflammation, and metabolic biomarkers in elderly tennis players. Methods: One hundred thirty-five long-term participants in elder tennis (>50 years old) were initially screened. Twenty-six eligible and voluntary subjects were divided into high tennis time group (HT) (14 ± 1.3 h/week) and low tennis time group (LT) (4.5 ± 0.7 h/week) by stratification analysis based on the amount of tennis playing activity time. The brachial-ankle pulse wave velocity (baPWV), blood pressure, ankle-brachial index (ABI), blood metabolic biomarkers, and insulin resistance were measured to compare the difference between HT and LT groups. Results: The baPWV was significantly lower in the HT group than that in the LT group (1283.92 ± 37.01 vs. 1403.69 ± 53.71 cm/s, p < 0.05). We also found that the HT insulin-resistant homeostasis model assessment (HOMA-IR) was significantly lower than that of LT (1.41 ± 0.11 vs. 2.27 ± 0.48 μIU/mL, p < 0.05). However, the blood lipid biomarkers (glucose, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride) were not statistical different between HT and LT groups (p > 0.05). Conclusion: We demonstrated that under the condition of similar daily physical activity level, elderly with a higher time of tennis-playing (HT group) exhibited relatively lower arterial stiffness (lower PWV) and lower insulin resistance compared to those with lower time tennis-playing (LT).


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Sheila M Manemann ◽  
Suzette J Bielinski ◽  
Ethan D Moser ◽  
Jennifer L St. Sauver ◽  
Paul Y Takahashi ◽  
...  

Background: Larger within-patient variability of lipid levels has been associated with an increased risk of cardiovascular disease (CVD). However, measures of lipid variability are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record (EHR)-based population cohort and assessed associations with incident CVD. Methods: We identified all individuals ≥40 years of age who resided in Olmsted County, MN on 1/1/2006 (index date) without prior CVD. CVD was defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention or stroke. Patients with ≥3 measurements of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides during the 5 years before the index date were retained in the analyses. Lipid variability was calculated using variability independent of the mean (VIM). Patients were followed through 9/30/2017 for incident CVD (including CVD death). Cox regression was used to investigate the association between quintiles of lipid VIMs and incident CVD. Results: We identified 18,642 individuals (mean age 60; 55% female) who were free of CVD at baseline and VIM calculated for at least one lipid measurement. After adjustment, those in the highest VIM quintiles of total cholesterol had a 25% increased risk of CVD (Q5 vs. Q1 HR: 1.25, 95% CI: 1.08-1.45; Table). We observed similar results for LDL-C (Q5 vs. Q1 HR: 1.20, 95% CI: 1.04-1.39) and HDL-C (Q5 vs. Q1 HR: 1.25, 95% CI: 1.09-1.43). There was no association between triglyceride variability quintiles and CVD risk. Conclusion: In a large EHR-based population cohort, high variability in total cholesterol, HDL-C and LDL-C was associated with an increased risk of CVD, independently of traditional risk factors, suggesting it may be a target for intervention. Lipid variability can be calculated in the EHR environment but more research is needed to determine its clinical utility.


BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e026860 ◽  
Author(s):  
Luqi Shen ◽  
José F Cordero ◽  
Jia-Sheng Wang ◽  
Ye Shen ◽  
Shengxu Li ◽  
...  

ObjectivesThe objective of this study was to evaluate the association of genetically determined leptin with lipids.DesignWe conducted a Mendelian randomisation study to assess a potential causal relationship between serum leptin and lipid levels. We also evaluated whether alcohol drinking modified the associations of genetically determined leptin with blood lipids.Setting and participants3860 participants of the Framingham Heart Study third generation cohort.ResultsBoth genetic risk scores (GRSs), the GRS generated using leptin loci independent of body mass index (BMI) and GRS generated using leptin loci dependent of BMI, were positively associated with log-transformed leptin (log-leptin). The BMI-independent leptin GRS was associated with log-transformed triglycerides (log-TG, β=−0.66, p=0.01), but not low-density lipoprotein cholesterol (LDL-C, p=0.99), high-density lipoprotein cholesterol (HDL-C, p=0.44) or total cholesterol (TC, p=0.49). Instrumental variable estimation showed that per unit increase in genetically determined log-leptin was associated with 0.55 (95% CI: 0.05 to 1.00) units decrease in log-TG. Besides significant association with log-TG (β=−0.59, p=0.009), the BMI-dependent GRS was nominally associated with HDL-C (β=−10.67, p=0.09) and TC (β=−28.05, p=0.08). When stratified by drinking status, the BMI-dependent GRS was associated with reduced levels of LDL-C (p=0.03), log-TG (p=0.004) and TC (p=0.003) among non-current drinkers only. Significant interactions between the BMI-dependent GRS and alcohol drinking were identified for LDL-C (p=0.03), log-TG (p=0.03) and TC (p=0.02).ConclusionThese findings together indicated that genetically determined leptin was negatively associated with lipid levels and the association may be modified by alcohol consumption.


2020 ◽  
Vol 14 (1) ◽  
pp. 39-45
Author(s):  
Noor Thair Tahir ◽  
Hind SH. Ahmed ◽  
Rasha K. Hashim ◽  
Teba D. Soluiman

Background: Obesity and type 2 diabetes have both rapidly raised during the last periods and are ongoing to increase at a disturbing rate universal. Several clinical and epidemiological researches demonstrated a reverse association between circulating vitamin D levels, central adiposity and the progress of insulin resistance and diabetes. Objective: The target of this work was to elucidate the complex role of vitamin D and the clinical implications of diabetes on metabolic defects related with obesity. Subjects and Methods: This study encompassed 90 diabetic patients (45 obese and 45 non obese) who were attending the National Diabetic Center/ Al-Mustansiriyah University during the period from June 2019 to January 2020; their age range was (35-60) years. All participant underwent clinical and biochemical examinations. Results: A substantial rise (p= 0.01) in waist/hip ratio, body mass index, fasting serum glucose, total cholesterol, triacylglycerol, and low density lipoprotein cholesterol in obese diabetic patients as paralleled to non-obese group. Moreover, there was an elevation in glycated hemoglobin, serum insulin, and homeostasis model assessment for insulin resistance in obese group, but it was not significant. A substantial decrease (p= 0.01) in serum high density lipoprotein cholesterol and vitamin D3 were detected in obese diabetic patients as paralleled to non-obese group.       Also, obese diabetic patients had the higher percent (61%) of D3 deficiency as paralleled to non-obese patients. Conclusions: In the present study, it is found that there is significant increase in blood sugar in the individuals with decreased vitamin D levels, which was related with insulin resistance, decreased β-cell function, and obesity.  


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4637 ◽  
Author(s):  
Xingchen Zhou ◽  
Wu Zhu ◽  
Minxue Shen ◽  
Yijing He ◽  
Cong Peng ◽  
...  

Background Acitretin is a second-generation synthetic retinoid, and is widely used for treating the severe psoriasis vulgaris. However, it should be chosen with caution for its cardiovascular risk, and it is reported that acitretin may increase the serum lipids. The purpose of this study is to investigate the relationship between the Frizzled-related proteins 4 (SFRP4) rs1802073 polymorphism and the changes of serum lipids in Chinese psoriatic patients during the treatment with acitretin. Methods In our study, 100 psoriatic patients were recruited systematically treated with acitretin (30 mg/day) for at least eight weeks. Data of the patients’ demographic and clinical characteristics and the results of serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were collected pre- and post-treatment. Results A total of 84 psoriatic patients were enrolled and divided into three groups by SFRP4 rs1802073 genotypes. The patients who carried with TT genotype had maintained levels of TG and LDL-C after acitretin treatment, while patients with GG/GT genotypes had significantly elevated levels of serum TG and LDL-C compared to the TT genotype (ΔTG%: 27.53 ± 59.13 vs −1.47 ± 37.79, p = 0.026, ΔLDL-C%: 10.62 ± 26.57 vs −1.29 ± 17.07, p = 0.042). The association of rs1802073 with TG and LDL-C profiles remained significant after adjusting for age, gender, and body mass index. Although without significance, the pre-post change in serum level of TC across rs1802073 GG/GT genotypes demonstrated a trend similar to TG and LDL, and the serum level of HDL-C demonstrated a trend opposite to TG, TC and LDL. Conclusions Our results demonstrated that SFRP4 rs1802073 polymorphism was found to be associated with elevated serum lipid levels after acitretin treatment, and it may serve as a genetic marker of safe and precise treatment for individual psoriatic patients.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Baishali M Ambegaonkar ◽  
Jaewhan Kim ◽  
Joseph Biskupiak ◽  
Vasilisa Sazonov

Elevated low density lipoprotein cholesterol (LDL-C), low high density lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG) are cardiovascular (CV) risk factors. The objective of this study was to evaluate attainment of goal/recommended lipid levels and predictors thereof post initiation of lipid modifying therapy (LMT) in a representative sample of US adults with commercial and government health insurance. Among 111,623 patients age >35 from GE Centricity Electronic Medical Records with ≥1 abnormal lipid value (before June 2004), we extracted 51,891 patients who initiated LMT between June 2004 and December 2006 (index date), continued therapy for 1 year, and had full lipid panels (LDL-C, HDL-C and TG) pre and post index date. LDL-C goals were defined according to NCEP ATP III guidelines. Recommended level for TG was <200 mg/dL, and for HDL-C >40mg/dL for men and >50mg/dL for women. Patients with history of coronary heart disease (CHD), diabetes and 10 year CHD risk>20% were classified as high CV risk. Multiple logistic regressions evaluated predictors of lipid level attainment (individual and ≥2). Among 51,891 patients, 53% had elevated LDL-C, 60% had low HDL-C, 37% had elevated TG and 73% had low HDL-C and/or elevated TG prior to LMT initiation. Despite 1 year therapy - with over 80% initiating statin therapy - 34% had elevated LDL-C (29% for high risk), 56% had low HDL-C (67% for high risk), 30% had elevated TG (32% for high risk) and 65% had low HDL-C and/or elevated TG (75% for high risk). CHD and diabetes were associated with better attainment of LDL-C goal and TG recommended levels. Females (Odds Ratio=0.24, 95% Confidence Interval [0.16 – 0.34]), patients with 10 year CHD risk>20% (OR=0.22, 95% CI [0.12– 0.40]) and those with higher baseline total cholesterol (OR=0.98, 95% CI [0.97– 0.99]) were less likely to attain ≥2 recommended lipid levels. In this cohort of insured US adults, additional 19% attained LDL-C goal following LMT for 1 year but few improved in terms of HDL-C (4%), TG (7%) and HDL-C and/or TG (8%). Additionally, dyslipidemia persisted among high risk patients despite higher likelihood of reaching LDL-C goal with presence of CHD or diabetes. Control of multiple lipid parameters remained poor.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Heesun Lee ◽  
Jun-bean Park ◽  
Hyo Eun Park ◽  
Su-yeon Choi ◽  
Kyungdo Han ◽  
...  

Background: Dyslipidemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We sought to investigate the risk of death and cardiovascular disease in relation to lipid components to establish evidence for primary prevention in young adults. Methods: In a nationwide cohort using the National Health Insurance claims database, we analyzed 5,688,055 statin-naïve subjects, aged 20-39 years, undergoing health check-up between 2009 and 2014. The study endpoint was a composite of clinical events, including death, myocardial infarction (MI), and stroke. We compared the incidence and the risk of clinical events according to lipid variables, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. Results: During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%); 16,262 deaths (0.29%), 8,578 MIs (0.15%), and 5,967 strokes (0.10%). The risk of clinical events gradually increased with increasing TC and triglycerides, and decreasing HDL-C, with a great contribution by MI. LDL-C had a J-shaped association with the study endpoint, showing the lowest risk in LDL-C of 84-101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted HR 1.20, p <0.001), after adjusting for conventional risk factors. Conclusions: In ‘statin-naïve’ young adults aged 20-39 years, the risk of clinical events was proportional to lipid levels; positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had the strongest and independent association with clinical events. Screening and intervention of abnormal lipid levels, particularly triglycerides, from an early age might be required.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gemma Ibáñez-Sanz ◽  
Anna Díez-Villanueva ◽  
Marina Riera-Ponsati ◽  
Tania Fernández-Villa ◽  
Pablo Fernández Navarro ◽  
...  

Abstract Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72–1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95–1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81–1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84–1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70–1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66–0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.


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