Users Of Lipid-lowering Drugs Research Articles

Specific Increase in Small Dense Low-Density Lipoprotein-Cholesterol Levels beyond Triglycerides in Patients with Diabetes: Implications for Cardiovascular Risk of MAFLD.

Small dense (sd) low-density lipoprotein (LDL)-cholesterol (C) is the most powerful predictor of cardiovascular (CV) disease among lipid biomarkers and is generated by hypertriglyceridemia and insulin resistance. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed liver disease with a high CV risk. We investigated the specific association of sdLDL-C with MAFLD beyond triglycerides (TG) and obesityMethods: Participants were 839 non-alcoholic drinkers with type 2 diabetes enrolled in a regional diabetes cohort. Fatty liver (FL) and visceral fat area (VFA) was detected by computed tomography scan. sdLDL-C and LDL-TG were measured by our established homogeneous assay. TG rich lipoprotein (TRL) was calculated by subtracting LDL-C plus HDL-C from total-C. Grade of sdLDL-C (≤ 24, 25-34, 35-44, and ≥ 45 mg/dL) was classified according to the Hisayama study. Compared to non-FL counterparts, FL subjects were younger, predominantly male and smokers; and had higher body mass index (BMI), VFA, hemoglobin A1c, C-peptide, TG, and sdLDL-C, while had similar levels of LDL-C, LDL-TG, and TRL-C. Multivariate logistic analysis revealed that sdLDL-C was the most powerful lipid parameter for identifying FL, independent of TG, HDL-C, BMI, and VFA. The independent association between TG and FL was lost when sdLDL-C was added to the analysis. These results remained the same when lipid-lowering drug users were excluded. After adjustment for confounders, the odds ratio for FL was 2.4-2.7 at sdLDL ≥ 35 mg/dL based on sdLDL ≤ 24 mg/dL. sdLDL-C levels are specifically elevated in patients with diabetes and MAFLD, independent of TG and VFA, suggesting liver-centered metabolic abnormalities.

Effect of Lipid-Lowering Drugs on Renal and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Dyslipidemia: ARetrospective Cohort Study.

The effects of lipid-lowering drugs (LLDs) on cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) and dyslipidemia are not completely understood. We conducted a retrospective cohort study to evaluate the effect of LLDs on end-stage kidney disease (ESKD), major adverse cardiovascular events (MACEs), and mortality in adult patients with CKD stage 3b, 4, or 5, and dyslipidemia. Participants were recruited between January 1, 2008, and December 31, 2018, and classified as LLD or non-LLD users; the final follow-up date was December 31, 2020. The primary outcome was time to ESKD or death due to renal failure. Sub-distribution hazard regression models adjusted for multivariables, including time-varying lipid profile covariates, were used for the analysis. Among the 6,740 participants, 4,280 patients with CKD and dyslipidemia, including 872 using LLDs and 3,408 not using LLDs, completed the primary analysis. The multivariable analyses showed that LLD users had a significantly lower risk of time to the composite renal outcome (adjusted hazard ratio [aHR], 0.76, 95% confidence interval [CI], 0.65-0.89), and MACE incidence (aHR, 0.75, 95% CI, 0.62-0.93) than did non-LLD users. After adjusting for time-varying covariates of the lipid profile, there was a significant difference in the composite renal outcome (aHR, 0.78, 95% CI, 0.65-0.93) and MACEs (aHR, 0.77, 95% CI, 0.60-0.98). Among adult patients with advanced CKD and dyslipidemia, LLD users had a significantly lower risk of composite renal outcomes and MACEs than non-LLD users. In addition to reducing lipid profile, the use of LLD is associated with renal and cardiovascular protective effects.

Statins were not associated with hepatocellular carcinoma after controlling for time-varying confounders in patients with diabetes

Background and ObjectivesWe examined the association between statin use and hepatocellular carcinoma (HCC) incidence in patients with diabetes using marginal structural models (MSMs) estimated by inverse probability weight (IPW), which adjusts for time-varying confounders that are also mediators, and we compared the results with conventional regression methods. MethodsThis retrospective cohort study included 245,122 patients with type 2 diabetes who were new users of lipid-lowering drugs identified using the claims data of a universal health insurance program. Statin exposure was time-updated every three months during the follow-up period. Stabilized IPW was calculated and accounted for chronic liver diseases considering as time-dependent confounders affected by past statin exposure. ResultsOver a median follow-up of 5.2 years, 1,694 patients developed HCC. In the conventional regression analysis, the hazard ratio of HCC associated with statin use was 0.88 (95% confidence interval CI: 0.79–0.97) after adjusting for baseline covariates and 0.97 (95% CI: 0.87–1.08) after additionally adjusting for time-varying covariates. The hazard ratio increased to 1.11 (95% CI: 0.94–1.31) using the MSM approach. ConclusionStatin use was not associated with the risk of developing HCC in patients with diabetes. Our findings highlight the importance of controlling time-varying confounders in observational studies.

A large remaining potential in lipid-lowering drug treatment in the type 2 diabetes population: A Danish nationwide cohort study.

To assess lipid-lowering drug (LLD) use patterns during 1996-2017 and examine lipid levels in relation to the use of LLDs and prevalent atherosclerotic cardiovascular disease (ASCVD). Using a nationwide diabetes register, 404 389 individuals with type 2 diabetes living in Denmark during 1996-2017 were identified. Individuals were followed from 1 January 1996 or date of type 2 diabetes diagnosis until date of emigration, death or 1 January 2017. Redemptions of prescribed LLDs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels were sourced from the National Laboratory Database since 2010. LLD coverage was calculated at any given time based on the redeemed amount and dose. Trends in lipid levels were estimated using an additive mixed-effect model. Low-density lipoprotein cholesterol (LDL-C) goal attainment was assessed based on recommended targets by the 2011, 2016 and 2019 guidelines for management of dyslipidaemias. LLD use has decreased since 2012 and only 55% of those with type 2 diabetes were LLD users in 2017. A decline in levels of total cholesterol and LDL-C, and an increase in triglycerides, was observed during 2010-2017. Annual mean levels of LDL-C were lower among LLD users compared with non-users (in 2017: 1.84 vs. 2.57 mmol/L). A greater fraction of LLD users achieved the LDL-C goal of less than 1.8 mmol/L compared with non-users (in 2017: 51.7% and 19%, respectively). Among LLD users with prevalent ASCVD, 26.9% and 55% had, as recommended by current 2019 European guidelines, an LDL-C level of less than 1.4 mmol/L and less than1.8 mmol/L, respectively, in 2017. LLD use and LDL-C levels are far from optimal in the Danish type 2 diabetes population and improvement in LLD use could reduce ASCVD events.

Identifying Clusters of Adherence to Cardiovascular Risk Reduction Behaviors and Persistence with Medication in New Lipid-Lowering Drug Users. Impact on Healthcare Utilization.

We sought to identify specific profiles of new lipid-lowering drug users based on adherence to a healthy lifestyle and persistence with medication, and to characterize co-morbidities, co-treatments, and healthcare utilization for each of the profiles identified. Observational study in 517 participants in the Aragon Workers’ Health Study (AWHS) without previous cardiovascular disease (CVD) and who initiated lipid-lowering therapy. Data were collected from workplace medical examinations and administrative health databases (2010–2018). Using cluster analysis, we identified distinct patient profiles based on persistence with therapy and lifestyle. We then compared characteristics, morbidity, and healthcare utilization across clusters. Participants were aggregated into four clusters based on persistence with therapy, smoking status, adherence to Mediterranean diet, and physical activity. In cluster 1 (n = 113), comprising those with a healthiest lifestyle (14.2% smokers, 84.0% with medium-high adherence to Mediterranean diet, high physical activity), 16.8% were persistent. In cluster 3 (n = 108), comprising patients with the least healthy lifestyle (100% smokers, poor adherence to the Mediterranean diet, low level of physical activity), all were non-persistent. Clusters 2 (n = 150) and 4 (n = 146) both comprised patients with intermediate lifestyle behaviors, but differed in terms of persistence (100 and 0%, respectively). Compared with other clusters, the burden of morbidity, cardiovascular score, and healthcare utilization were lower in cluster 1. The healthy adherer effect was only observed in new lipid-lowering drug users of certain profiles. Furthermore, we found that differences in adherence to lifestyle and medication recommendations for CVD prevention influenced morbidity burden and healthcare utilization.

Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes: a comparative cross-sectional study

BackgroundThe receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D).MethodsCross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed.ResultsIn this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P < 0.001), and triglycerides (P < 0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD.ConclusionsHigher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.

New Male Users of Lipid-Lowering Drugs for Primary Prevention of Cardiovascular Disease: The Impact of Treatment Persistence on Morbimortality. A Longitudinal Study

The objective of this study was to analyse persistence to lipid-lowering drug use for primary prevention of cardiovascular disease (CVD) in a new users cohort, to explore all-cause and cardiovascular related morbidity, comorbidity and mortality in this group and, finally, to study the relationship between persistence and morbimortality. We selected subjects who started lipid-lowering treatment for primary prevention of CVD between 1 January 2010 and 31 December 2017 (N = 1424), and classified them as treatment-persistent or -nonpersistent. Bivariate analyses were performed to compare sociodemographic and clinical variables, morbimortality and time to event between groups. The association between morbidities was explored using comorbidity network analysis. The effect of persistence was analysed using logistic regression and Cox survival analyses. Only 38.7% of users were persistent with treatment. Persistent and nonpersistent users had similar sociodemographic and clinical profiles, although differed in age, smoking status, and glycemia. Comorbidity networks revealed that the number of co-occurring diagnoses was higher in nonpersistent than persistent users. Adjusted analyses indicated a protective effect of treatment persistence, especially against major adverse cardiovascular events (MACE), but this effect was not statistically significant. Observational studies are crucial to characterize real-world effectiveness.

Association between exposure to perfluoroalkyl substances and metabolic syndrome and related outcomes among older residents living near a Science Park in Taiwan

Perfluoroalkyl substances (PFASs) are an emerging class of artificial environmental chemicals that have multiple potentially harmful effects on health. The largest Science Park in Taiwan discharges wastewater containing PFASs into the Keya River, and a high concentration of PFASs has been found in this river and its aquatic creatures. We conducted a cross-sectional study from 2016 to 2017 of 397 subjects aged 55-75 years living near the river and evaluated the association of PFASs with metabolic syndrome and related outcomes. The results indicated that perfluorooctane sulfonate (PFOS) levels were positively associated with serum low-density lipoprotein (LDL) levels (P for trend=0.03) and that perfluorononanoic acid (PFNA) and PFOS levels were positively correlated with uric acid levels (P for trend=0.03 and 0.03). Perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA) levels were negatively associated with serum triglyceride levels (P for trend=0.014 and<0.01). After excluding lipid-lowering drug users, the association between certain PFAS levels and the LDL level was significantly enhanced, but the downward trends of serum triglyceride levels were weakened. When stratified by sex, PFNA (P for trend <0.01), perfluorohexanesulfonate (PFHxS) (P for trend <0.01), and PFOS (P for trend <0.01) showed positive associations with the uric acid level only among males. In conclusion, our results showed that associations were consistently null between PFASs and metabolic syndrome. PFAS levels were associated with serum lipids, and lipid-lowering drugs may interfere with this relationship. Certain PFASs were found to be positively associated with uric acid levels, especially in males. Further studies are warranted to clarify the causal relationships.

137-OR: Trends in Lipid Levels Relative to Lipid-Lowering Drug Use among Danish Type 2 Diabetes Subjects

Background: Lipid-lowering treatment is crucial in preventing cardiovascular disease in type 2 diabetes subjects. It is unknown how well treatment guidelines translate into clinical practice. We examined measured lipid levels in relation to use of lipid-lowering drugs among type 2 diabetes subjects in Denmark from 2010 to 2017. Methods: The study population consisted of 404,389 subjects with type 2 diabetes living in Denmark between 1996 and 2017 identified using the Danish Diabetes Register. Redemptions of prescribed lipid-lowering drugs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels was sourced from the National Laboratory Database containing detailed information on laboratory measurements at major clinical laboratories since 2010. A drug-exposure function was developed and applied to examine follow-up of lipid-lowering drug coverage at any given time based on the redeemed amount and dose of lipid-lowering drugs. Annual mean lipid levels were obtained by calculating the mean lipid measurement value per subject, per calendar year, and per lipid type. Proportions of subjects within LDL thresholds were calculated according to thresholds defined by 2019 European Society of Cardiology dyslipidemia guidelines. Results: In total, 64% of subjects redeemed at least two prescriptions of lipid-lowering drugs during the study period. A decline in levels of total-cholesterol and LDL was observed in the years from 2010 to 2017 in users and non-users of lipid-lowering drugs. Annual mean LDL levels were lower among lipid-lowering drug users compared with non-users (in 2017: 1.84 and 2.57 mmol/L, respectively). A greater fraction of lipid-lowering drug users achieved the LDL goal of &amp;lt;1.8 mmol/L compared with non-lipid-lowering drug users (in 2017: 51.7% and 19%, respectively). Conclusions: Lipid-lowering drug use and LDL levels are far from optimal in the Danish type 2 diabetes population and constitute a large potential for improvement. Disclosure H. Amadid: None. M. Bekker-Nielsen Dunbar: None. P.F. Rønn: Research Support; Self; Amgen, Danish Diabetes Academy. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J.S. Knudsen: None. B. Carstensen: Stock/Shareholder; Self; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; Amgen, AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Amgen Inc.

Lipid-lowering drugs and the risk of cataract: An Observational Post Marketing Study

The risk of cataracts (C) associated to lipid-lowering drugs (LLD) is discussed. Following early warnings in animal models, several clinical and observational studies led to conflicting results. We assessed in real life the association between LLD and C using the WHO individual case safety reports database, VigiBase®, including reports from over 130 countries worldwide. We performed a disproportionality analysis with all reports between 1/1/1988 and 31/12/2018 to measure the reporting risk of “cataract” in patients ≥ 45 years. Primary analysis compared LLD users to non-users. We performed 2 sensitivity analyses: (1) exclusion of reports with 2 LLD associated, (2) exclusion of patients with antidiabetics and glucocorticoids, known to induce C. Finally, we investigated the drugs more at risk in each class. We identified 14,664 reports of cataract (3,049 in users, 66% women, 66 ± 20 y). The most frequently involved LLD were statins [84%, atorvastatin (n = 1.016), simvastatin (626), rosuvastatin (392), lovastatin (343), pravastatin (268)] followed by fibrates [5.7%, fenofibrate (117), gemfibrozil (56)], nicotinic acid (3%), bile acid sequestrants (2%), herbal cholesterol and triglyceride reducers (2%) and others (15%). LLD users were associated to a greater C risk than non-users ROR: 2.47 (95%CI: 2.37–2.57). This risk was also found for statins in general, fibrates, bile sequestrants, nicotinic acid, herbal drugs and others (ezetimibe, PCSK9 inhibitors). Similar trends were observed in sensitivity analyses. The most important risk was found for statins with lovastatin followed by pravastatin and atorvastatin and for fibrates with fenofibrate. Using a large real life database (18.5 million reports), we found for the first time a signal of cataract for all LLD, i.e. not only statins but also fibrates and other classes suggesting that a decrease in cholesterol is involved in the pathophysiology of C with LLD.

Optimal threshold of adherence to lipid lowering drugs in predicting acute coronary syndrome, stroke, or mortality: A cohort study.

ObjectiveThresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension.DesignCohort study of new users of LLDs.SettingComprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016.ParticipantsPatients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded.Main outcomes measuresHospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality.Statistical analysisAdherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment.Results52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51–0.54), 0.79 (0.45–0.87), and 0.84 (0.79–0.89), respectively. These results were consistent among patients aged ≥ 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low.ConclusionIn new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality.

Are lipid-lowering drugs associated with a risk of cataract? A pharmacovigilance study.

Some reports have raised concerns regarding a potential risk of cataracts associated with statins. However, clinical and observational studies evaluating the risk led to conflicting results. We assessed whether lipid-lowering drugs (LLD) use is associated with an increased risk of cataract using the WHO's Individual Case Safety Reports database, VigiBase® . We performed a disproportionality analysis with all reports between 1/1/1988 and 12/31/2018 to measure the reporting risk of 'cataract' in patients ≥45years. Primary analysis compared LLD users to non-users. To mitigate some potential confounding bias, we performed several sensitivity analyses excluding reports (i) with an association of at least two LLD, (ii) with antidiabetic and glucocorticoids and (iii) with lovastatin. We also analyzed the data according to the different classes of age limiting the period of study to years 2002-2012. We identified 14664 reports of cataract (3049 in LLD users, 66% women, 66±20years). Statins (84%, atorvastatin, simvastatin, rosuvastatin and lovastatin) were mostly reported, followed by fibrates (5.7%), nicotinic acid (3%), bile acid sequestrants (2%), herbal cholesterol and triglyceride reducers (2%) and others (ezetimibe, PCSK9 inhibitors, 15%). LLD users were associated with a greater risk of reports than non-users (ROR 2.47, 95% CI 2.37-2.57). This association was also found for statins in general, fibrates, bile sequestrants, nicotinic acid, herbal drugs and others. Similar trends were observed in sensitivity analyses (except for fibrates and nicotinic acid after exclusion of reports with at least two LLD or in older patients ≥75years). Using a large real-life database (>18.5 million reports), we found a signal of cataract for LLD as a whole and statins, bile sequestrants and herbal drugs in particular. The signal disappeared for fibrates and nicotinic acid in older patients. No definite conclusions can be made for ezetimibe or PCSK9 inhibitors (evolocumab and alirocumab). This suggests that a decrease in cholesterol could be important in the pathophysiology of cataract in patients exposed to the main LLD.

Diet and lipid-lowering drug use among people with dyslipidemia in Korea.

Obesity and diet contribute to the development of hypercholesterolemia; therefore, controlling blood lipid concentration through diet is essential. To understand the role of diet in controlling blood lipid concentration, we evaluated the food and nutrient intakes, anthropometry, and blood lipid concentrations of adults with dyslipidemia with or without lipid-lowering drug use. For this crosssectional study, three-year data were obtained from the 6th-7th Korean National Health and Nutrition Examination Survey (2015-2017). Patients with dyslipidemia were categorized as users (1,734) or nonusers (856) of lipidlowering drugs. Age, education level, marital status, self-reported health status, hypertension, diabetes, and alcohol intake were significantly different between users and nonusers (p<0.05). Multiple logistic regression analysis revealed a significant association between hypertension and diabetes and blood cholesterol status among users. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were significantly lower in users than in nonusers. During the study period, intake of saturated fatty acids increased significantly among users and nonusers, and intakes of vitamins A and C decreased significantly with potential detrimental health effects. However, intakes of n-3 fatty acids and dietary fiber significantly increased in users and nonusers with potential health benefits. Intakes of vegetables and fish significantly increased in users. No associations were observed between intakes of nuts, fruits, or vegetables and blood cholesterol status. Changes in personal behaviors of dyslipidemic patients need reinforcement for effective blood lipid management, particularly for optimal food intake patterns, whether lipid-lowering drug users or nonusers.

Investigation of the prevalence of Cognitive Impairment and its risk factors within the elderly population in Shanghai, China

To investigate the prevalence of cognitive impairment and its risk factors among Chinese elders aged over 80 years, a community-based, cross-sectional study was conducted from May to June 2016 in Shanghai, China. Cognitive function was measured by using Mini-Mental Status Examination. Multiple logistic regression assessed associations between risk factors and cognitive impairment. Of 480 participants, 30% were diagnosed with cognitive impairment. Women [adjusted odds ratio (AOR): 1.71, 95% confidence interval (CI): 1.03–2.83], solitary life (AOR: 3.15, 1.89–5.26), monthly income less than 2000 Chinese yuan (AOR: 3.47, 1.18–10.23) were significantly associated with increased risk of cognitive impairment, compared with men, non-solitary life, and monthly income greater than 4000 Chinese yuan, respectively. Overweight (AOR: 0.59, 0.36–0.97), being physically active at least 60 minutes per day (AOR: 0.59, 0.35–0.95), antihypertensive drugs users (AOR: 0.45, 0.28–0.72), and lipid lowering drugs users (AOR: 0.21, 0.06–0.76) significantly lowered the risk of cognitive impairment, compared with normal weight, inadequate outdoor activity, and non-medication users, respectively. Accordingly, this study found that women, solitary life, lower income was associated with increased risk of cognitive impairment, while overweight, being physically active, and antihypertensive and lipid lowering drugs usage might lower the risk.

Abstract P102: Longitudinal and Secular Decrease in Total Cholesterol Levels in All Birth Cohorts. The Tromsø Study 1979-2008

Introduction: Elevated blood cholesterol is a modifiable risk factor for cardiovascular disease (CVD). Surveillance of cholesterol levels is needed to study disease burden, consider priorities for CVD prevention and intervention, and understand the effect of diet, lifestyle and medication use. Previous studies show a cholesterol level decline in recent decades, but lack data to follow individuals from different birth cohorts from early and middle adulthood to older age. Hypothesis: To assess secular and longitudinal trends in total cholesterol levels. Methods: We investigated changes in age-specific cholesterol levels by repeated measurements in 37,968 women and men born 1905-1977 examined up to five times between 1979 and 2008 in the population-based Tromsø Study. Results: Mean total cholesterol decreased from 1979 to 2008 in both genders in all age groups. The decrease in age group 40-49 years was 1.2 mmol/l in women and 1.0 mmol/l in men. Both the 80th percentile and the 20th percentile of the population cholesterol distribution decreased. In birth cohorts born 1940-77, mean total cholesterol levels increased with age up to 2001 and decreased thereafter to 2007. Among those born 1910-39, the cholesterol decrease was evident after 1994-95. The longitudinal trends in those born 1940-77 were not influenced by use of lipid-lowering drugs, while the decrease with age in birth cohorts born 1910-39 was slightly weaker among never users of lipid-lowering drugs compared to the total sample. Conclusions: A longitudinal decrease in mean cholesterol levels was observed from 1994-95 or from 2001 depending on birth cohort. A secular decrease was observed from 1979-80 in all age groups. The findings points to a mass population effect rather than a treatment effect of high-risk individuals alone.

Comparing the Trend of Physical Activity and Caloric Intake between Lipid-Lowering Drug Users and Nonusers among Adults with Dyslipidemia: Korean National Health and Nutrition Examination Surveys (2010-2013).

BackgroundThe purpose of this study was to compare the physical activity and caloric intake trends of lipid-lowering drug users with those of non-users among Korean adults with dyslipidemia.MethodsThis study was a repeated cross-sectional study with a nationally representative sample of 2,635 Korean adults with dyslipidemia based on the 2010–2013 Korea National Health and Nutrition Examination Survey. Physical activity was assessed using the International Physical Activity Questionnaire, and caloric intake was estimated through 24-hour dietary recall. All statistical analyses were conducted using IBM SPSS ver. 21.0 (IBM Co., Armonk, NY, USA). The changes in physical activity and caloric intake were investigated for lipid-lowering drug users and non-users using generalized linear models.ResultsThe proportion of lipid-lowering drug users in the 2010–2013 survey population increased from 3.5% to 5.0% (P<0.001). Among adults of dyslipidemia, total of 1,562 participants (56.6%) reported taking lipid-lowering drugs, and 1,073 (43.4%) reported not taking lipid-lowering drugs. Drug users were more likely to be older and less educated and to have a diagnosis of diabetes, higher body mass index, and lower low density lipoprotein cholesterol level. Physical activity trends were tested separately for the lipid-lowering drug users and non-users, and a significant decrease was found among the drug users during the study period. Physical activity among the drug users in 2013 was 38% lower (1,357.3±382.7 metabolic equivalent [MET]; P for trend=0.002) than in 2010 (2,201.4±442.6 MET). In contrast, there was no statistically significant difference between drug users and non-users in the trend of caloric intake during the same period.ConclusionPhysical activity significantly decreased among lipid-lowering drug users between 2010 and 2013, which was not observed among non-users. The importance of physical activity may need to be re-emphasized for lipid-lowering drug users.

Trends in cardiovascular risk factors across levels of education in a general population: is the educational gap increasing? The Tromsø study 1994–2008

BackgroundTo describe trends in cardiovascular risk factors and change over time across education levels, and study the influence from medicine use and gender.MethodsData from participants (30–74 years) of the Tromsø...

Lipid-Lowering Drugs Associated With Slower Motor Decline in the Elderly Adults

Vascular risk factors contribute to motor decline in the elderly persons. We investigated the relationship between lipid-lowering drugs (LLDs) use and decline in walking speed (WS) in older adults. Data on 4,009 community-dwelling men and women, aged ≥65 years at baseline, are drawn from the Dijon (France) center of the Three-City study. "Fast" WS was assessed over 6 m at baseline and at 4, 6, 8, and 10 years of follow-up. Mixed linear models were used to determine the relationship between LLDs and change in WS over the follow-up. At baseline, 1,295 (32%) participants used LLDs (statins, n = 643; fibrates, n = 652); mean fast WS was 152.9cm/s and not significantly different between LLDs users and nonusers. In models adjusted for age, sex, cholesterol level, and other covariates, WS decline was 25% slower in LLDs users (difference with nonusers: 0.58cm/s/y, 95% CI: 0.30, 0.86; p < .001). Both fibrates and statins were associated with slower decline, but only the effect of statins was robust in analyses that took missing values into account. The beneficial effect was more pronounced in those on LLDs continuously over the follow-up. Fast WS declined less in those on LLDs, suggesting that the effect of LLDs, statins in particular, extend beyond that on cardiovascular disease in the elderly persons. However, these effects were modest and their clinical relevance is unclear.

Lipid parameters, lipid lowering drugs and the risk of venous thromboembolism

BackgroundBesides their effects on atherogenesis, lipids and lipoproteins could contribute to the development of venous thromboembolism (VTE). This association has been investigated in a few studies with conflicting results. MethodsPlasma levels of total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I and apolipoprotein B were measured in 467 patients with a first unprovoked VTE event diagnosed between May 2000 and December 2004 and in 467 age and sex matched controls. The association between these parameters and VTE was determined in non-users of lipid lowering drugs (LLD), in statin users and in fibrate users in a quartile-based analysis. We repeated this stratified analysis within each stratum of men and women. ResultsThe median age of patients was 73 years [interquartile range 58–80], 41.5% were men. Among the 934 patients of the study, 100 were treated with statin, 91 with fibrate and 743 were not receiving LLD. Among non users of LLD, high levels of apolipoprotein B were associated with VTE (OR 1.82, 95% CI 1.19–2.79) after adjustment for age and body mass index. Elevated LDL-cholesterol levels were associated with VTE only in men (OR 2.32, 95% CI 1.07–5.01). High levels of LDL/HDL-cholesterol and apolipoprotein B/apolipoprotein A-I ratios were associated with VTE (OR 2.76, 95% CI 1.69–4.50 and OR 1.86, 95% CI 1.16–2.97 respectively) but this effect was mainly observed in men. There was no association between lipid parameters and VTE in statin users and in fibrate users. ConclusionOur results are in line with the new concept of a global cardiovascular disease combining atherosclerosis and VTE.

282 Ten-year risk of cancer mortality according to lipid levels and use of lipid-lowering drugs in the French general population

Purpose The beneficial effect of lipid-lowering drugs on cardiovascular mortality is well established, but long term safety data remain scarce. The aim of this study was to assess 10-year risk of cancer mortality according to blood lipid levels and lipid-lowering drug exposure, in the French general population. Methods Our analysis was based on the Third French MONICA Cross-sectional survey on cardiovascular risk factors (1995-1996). Participants aged 35-64 years were randomly recruited from French polling lists. Subjects with a history of cancer at baseline were excluded from the analysis. Vital status and cause of mortality were obtained 10 years after inclusion. Results There were 3262 participants and 177 deaths were recorded (78 due to cancer). The sample was mainly composed of subjects in primary cardiovascular prevention (96%) and comprised 64% of normolipidemic, 25% of untreated dyslipidemic (total cholesterol ≥ 6.5 mmol/L or triglycerides ≥ 3.5 mmol/L) and 11% of dyslipidemic subjects treated with a lipid-lowering drug (4% statin, 6% fibrate). After adjustment for centre, age, smoking, gamma-glutamyl transpeptidase and mean corpuscular volume, which were all significantly associated with cancer mortality, the hazard ratio (HR) for cancer mortality in subjects with non HDL-cholesterol Conclusion In this cohort mainly composed of primary prevention subjects, low HDL- and low non HDL-cholesterol levels were associated with increased cancer mortality, whereas risk of cancer death was reduced in users of lipid-lowering drugs. This suggests that the impact of low cholesterol on cancer risk may be different in subjects with spontaneously low levels and in those for whom cholesterol is lowered by lipid-lowering drugs.