Lipid-Lowering Drug Use and Cancer Incidence and Mortality in the ARIC Study
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ABSTRACT: Background
Lipid-lowering drugs, particularly statins, are associated with reduced
SUBMITTER: Marrone M
PROVIDER: S-EPMC8562700 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lipid-lowering medications, particularly statins, may protect against aggressive prostate cancer. Fatal prostate cancer, the most clinically relevant outcome, remains understudied for this association. We prospectively studied lipid-lowering medication use and both incident and fatal prostate cancer in black and white men in the Atherosclerosis Risk in Communities (ARIC) study. A total of 6,518 men without cancer at visit 2 (1990-1992), the start of the statin era, were followed for prostate cancer incidence and death through 2012. Medication use was collected during study visits and telephone calls at up to nine time points during follow-up. Cox regression was used to estimate HR and 95% confidence intervals (CI) of total (white N = 541, black N = 259) and fatal (white N = 56, black N = 34) prostate cancer overall and by race. Lipid-lowering medication use was modeled as time-dependent current use or duration (never, <10, and ?10 years). By visit 4 (1996-1998), 21% of white and 11% of black men had used a lipid-lowering medication, mostly statins. There was a suggestion that current users were less likely to die from prostate cancer than nonusers (HR = 0.67, 95% CI = 0.42-1.07) after multivariable adjustment. We observed no statistically significant differences between black and white men. Current use was not associated with incident prostate cancer, although long-term use was statistically significantly inversely associated with incidence (HR = 0.68; 95% CI = 0.50-0.92). Long-term lipid-lowering medication use was associated with lower risk of prostate cancer. Current use was possibly associated with fatal prostate cancer.
| S-EPMC6289799 | biostudies-literature
Project description:BackgroundStatins have demonstrated protection against aggressive/late-stage and/or lethal prostate cancer (PC), but prior studies are limited by small populations, short follow-up and unequal health-care access. Research has not demonstrated that non-statin lipid-lowering medications (NSLLMs) provide a similar benefit, which would support a cholesterol-based mechanism. We sought to rigorously test the hypothesis that cholesterol-lowering drugs affect PC incidence and severity.MethodsA retrospective cohort study was conducted by abstracting prescription and health service records for 249,986 Saskatchewan men aged ≥40 years between January 1, 1990 and December 31, 2014 and comparing first-time statin and NSLLM users with age-matched non-users and glaucoma medication (GM) users for PC incidence, metastases at diagnosis and PC mortality using Cox proportional hazards regression.ResultsIn comparing statin users to non-users, a weak association was detected with increased PC incidence (hazard ratio [HR] 1.07, 95% confidence interval [CI]: 1.02-1.12) that disappeared when compared with GM users. Substantial protective associations were observed between statin use and metastatic PC and PC mortality (HRs 0.69, 95% CI: 0.61-0.79 and 0.73, 95% CI: 0.66-0.81, respectively), which were stronger when compared with GM use (HRs 0.52, 95% CI: 0.40-0.68 and 0.51, 95% CI: 0.41-0.63, respectively). Similar associations were found for NSLLM versus GM for metastatic PC (HR 0.57, 95% CI: 0.41-0.79) and PC mortality (HR 0.66, 95% CI: 0.51-0.85).ConclusionsOur analyses provide one of the more comprehensive findings to date that statins may reduce risk of metastatic PC and PC mortality, and the first to demonstrate that NSLLM have similar effects, supporting a cholesterol-based mechanism.
| S-EPMC6501826 | biostudies-literature
Project description:PurposePrior studies conducted primarily in white populations have suggested that pre-diagnostic cholesterol lowering drugs (CLDs) improved survival among women with breast cancer (BC). However, this association had not been well characterized in diverse racial/ethnic populations. We investigated whether pre-diagnostic CLD use is associated with all-cause and BC-specific mortality among female BC cases of the Multiethnic Cohort (MEC).MethodsCLD use was ascertained through questionnaires administered in 2003-2008. A total of 1448 incident BC cases were identified by linkage to SEER cancer registries in Hawaii and California from 2003 to 2014. Multivariable Cox regression was conducted to estimate hazard ratios (HR) and 95% confidence intervals (CI) of the associations of pre-diagnostic CLD use with all-cause and BC-specific mortality, adjusting for tumor characteristics, first course of treatment, health behaviors, co-morbidities, and demographics. Subgroup analyses by stage and hormone receptor status were conducted for all-cause mortality.ResultsThere were 224 all-cause and 87 BC-specific deaths among the 1448 BC cases during a median follow-up of 4.5 years after diagnosis. Women with BC who ever used CLDs had a 27% lower hazard of all-cause mortality (HR 0.73, 95% CI 0.54-0.98) and 17% lower hazard of BC-specific mortality (HR 0.83, 95% CI 0.49-1.39) compared to never users. CLD use reduced mortality among women with advanced-stage tumors and hormone receptor-positive breast tumors (HR 0.54 95% CI 0.33-0.90; HR 0.69, 95% CI 0.48-0.99, respectively).ConclusionThese findings demonstrate an improved survival associated with CLD use prior to diagnosis in a multiethnic population of women with BC.
| S-EPMC8557195 | biostudies-literature
Project description:BackgroundIn people living with HIV (PLWH), statins may be disproportionately effective but remain underutilized. A large prospective trial in patients with low to moderate cardiovascular (ASCVD) risk will reveal whether they should be considered in all PLWH. But its effect size may not apply to real-world PLWH with higher ASCVD and mortality risk. Also, the clinical role of non-statin lipid-lowering therapy (LLT) and LLT adherence in this population is unknown.MethodsComparative multi-level marginal structural model for all-cause mortality examining four time-updated exposure levels to LLT, antihypertensives, and aspirin in a virtual cohort of older PLWH. Incident coronary, cerebrovascular, and overall ASCVD events, serious infections, and new cancer diagnoses served as explanatory outcomes.ResultsIn 23,276 HIV-infected US-veterans who were followed for a median of 5.2 years after virologic suppression overall mortality was 33/1000 patient years: > 3 times higher than in the US population. Use of antihypertensives or aspirin was associated with increased mortality. Past LLT use (> 1 year ago) had no effect on mortality. LLT exposure in the past year was associated with a reduced hazard ratio (HR) of death: 0.59, 95% confidence interval (CI) 0.51-0.69, p < 0.0001 for statin containing LLT and 0.71 (CI: 0.54-0.93), p = 0.03 for statin-free LLT. For consistent LLT use (> 11/12 past months) the HR of death was 0.48 (CI: 0.35-0.66) for statin-only LLT, 0.34 (CI: 0.23-0.52) for combination LLT, and 0.27 (CI: 0.15-0.48) for statin-free LLT (p < 0.0001 for all). The ASCVD risk in these patients was reduced in similar fashion. Use of statin containing LLT was also associated with reduced infection and cancer risk. Multiple contrasting subgroup analyses yielded comparable results. Confounding is unlikely to be a major contributor to our findings.ConclusionsIn PLWH, ongoing LLT use may lead to substantially lower mortality, but consistent long-term adherence may be required to reduce ASCVD risk. Consistent non-statin LLT may be highly effective and should be studied prospectively.
| S-EPMC7866454 | biostudies-literature
Project description:AimWe investigated the association between total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride (TG) variability and cancer patient mortality risk.MethodsWe retrospectively analyzed 42,539 cancer patients who were not receiving lipid-lowering agents and who had at least three TC measurements within 2 years of their initial cancer diagnosis. Using a multivariable Cox regression model, the risk of mortality was evaluated.ResultsIn multivariable analysis, Q2 (adjusted hazard ratio [aHR]: 1.32, 95% confidence interval (CI): 1.24-1.41), Q3 (aHR: 1.66, 95% CI: 1.56-1.76), and Q4 (aHR: 1.96, 95% CI: 1.84-2.08) of coefficient of variation (CV) in TC were significantly associated with mortality risk compared to Q1, showing a linear association between higher TC variability and mortality (P for trend<0.001). Q2 (aHR: 1.34, 95% CI: 1.06-1.77), Q3 (aHR: 1.40, 95% CI: 1.06-1.85), and Q4 (aHR: 1.50, 95% CI: 1.14-1.97) were all significantly associated with a higher risk of death compared to Q1 in multivariable Cox regression for the association between CV in LDL and all-cause mortality (P for trend=0.005).ConclusionIn cancer patients who do not receive lipid-lowering agents, high variability in total cholesterol and LDL cholesterol levels was found to pose significant role in mortality risk.
| S-EPMC10586791 | biostudies-literature
Project description:Parkinson's disease (PD) affects millions of individuals worldwide, and it is the second most common late-onset neurodegenerative disorder. There is no cure and current treatments only alleviate symptoms. Modifiable risk factors have been explored as possible options for decreasing risk or developing drug targets to treat PD, including low-density lipoprotein cholesterol (LDL-C). There is evidence of sex differences for cholesterol levels as well as for PD risk. Genetic datasets of increasing size are permitting association analyses with increased power, including sex-stratified analyses. These association results empower Mendelian randomization (MR) studies, which, given certain assumptions, test whether there is a causal relationship between the risk factor and the outcome using genetic instruments. Sex-specific causal inference approaches could highlight sex-specific effects that may otherwise be masked by sex-agnostic approaches. We conducted a sex-specific two-sample cis-MR analysis based on genetic variants in LDL-C target encoding genes to assess the impact of lipid-lowering drug targets on PD risk. To complement the cis-MR analysis, we also conducted a sex-specific standard MR analysis (using genome-wide independent variants). We did not find evidence of a causal relationship between LDL-C levels and PD risk in females [OR (95% CI) = 1.01 (0.60, 1.69), IVW random-effects] or males [OR (95% CI) = 0.93 (0.55, 1.56)]. The sex-specific standard MR analysis also supported this conclusion. We encourage future work assessing sex-specific effects using causal inference techniques to better understand factors that may contribute to complex disease risk differently between the sexes.
| S-EPMC9477004 | biostudies-literature
Project description:Drug-induced myopathies are classified as acquired myopathies caused by exogenous factors. These pathological conditions develop in patients without muscle disease and are triggered by a variety of medicaments, including lipid-lowering drugs (LLDs) such as statins, fibrates, and ezetimibe. Here we summarise the current knowledge gained via studies conducted using various models, such as cell lines and mammalian models, and compare them with the results obtained in zebrafish (Danio rerio) studies. Zebrafish have proven to be an excellent research tool for studying dyslipidaemias as a model of these pathological conditions. This system enables in-vivo characterization of drug and gene candidates to further the understanding of disease aetiology and develop new therapeutic strategies. Our review also considers important environmental issues arising from the indiscriminate use of LLDs worldwide. The widespread use and importance of drugs such as statins and fibrates justify the need for the meticulous study of their mechanism of action and the side effects they cause.
| S-EPMC8198905 | biostudies-literature
Project description:Hyperlipidemia is common in patients with intracerebral hemorrhage (ICH). Accumulating evidence indicates that patients with ICH are at risk for future hemorrhage recurrence, cardiovascular disease, and ischemic stroke and highlights the importance of secondary prevention of vascular events after ICH. Although the benefits of intensive treatment of hyperlipidemia for reducing ischemic cardiac and vascular events in patients with ischemic stroke are well established, the benefit versus harm in patients with ICH are less clear. Epidemiological studies suggest that hyperlipidemia is protective against ICH and that intensive lowering of lipids is associated with increased risk for ICH. Similarly, although currently available lipid-lowering treatments have been thoroughly studied in patients with ischemic cardiac and vascular disease, only few randomized trials of these therapies included a very small number of patients with history of ICH. Thus, limiting any definitive conclusions regarding the safety and net benefit of these treatments in ICH populations. Currently, there is no consensus regarding the optimal strategy for management of hyperlipidemia after ICH. In this article, we review relevant literature to outline the competing risks and benefits of lipid-lowering treatments in this vulnerable patient population. We suggest a treatment paradigm based on available data but note that data from dedicated randomized trials are needed to build the necessary evidence to guide optimal lipid-lowering strategy in patients with a history of ICH.
| S-EPMC9248990 | biostudies-literature
Project description:Purpose:To assess the association between diabetes mellitus (DM) and the incidence of cancer at different sites. Methods:Data from the baseline and first three follow-up visits of the Atherosclerosis Risk in Communities (ARIC) study, an ongoing cohort study of adults from four American communities, were used in this study. Of 15,792 persons aged 45-64 years old who participated in the baseline visit, the data of 15,118 participants were available for this study. For each cancer site, a conditional stratified Poisson regression model was fitted to estimate the adjusted relative rate and 95% confidence interval (adj. RR, 95% CI) of its incidence in diabetics compared to non-diabetics. Results:We excluded 850 participants with a history of cancer at baseline and 149 participants who developed cancer during 2 years after enrollment, leaving a total of 14,119 participants of whom 1721 were diabetics. Independent of age, body mass index, alcohol consumption, and physical activity, DM decreased the risk of all cancers combined (adj. RR: 0.77, 95% CI: 0.60, 0.98) and the risk of prostate cancer (adj. RR: 0.51, 95% CI: 0.27, 0.97) and increased the risk of colorectal cancer in non-menopausal women (adj. RR: 12.08, 95% CI: 2.06, 70.94). Conclusions:In conclusion, DM may be associated with an increased risk of colorectal cancer in non-menopausal women and a decreased risk of prostate cancer and all cancers combined.
| S-EPMC6582039 | biostudies-literature
Project description:BackgroundInflammatory bowel disease (IBD) has been associated with lipid-lowering drugs in observational studies. Drug-target Mendelian randomization (MR) was utilized in this study to examine the causal relationship between lipid-lowering drugs and incidence of IBD, aiming to identify new preventive uses for the drugs.MethodsWe identified instrumental variables for three classes of lipid-lowering drugs: HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors, using data from the Global Lipids Genetics Consortium. Summary statistics of IBD were obtained from UK Inflammatory Bowel Disease Genetics. The summary-data-based MR (SMR) and the inverse-variance weighted (IVW) MR were used for analysis. Sensitivity analyses were performed by conventional MR methods.ResultsThe SMR analysis showed no significant genetic association between increased gene expression of HMGCR, PCSK9, and NPC1L1 and IBD, Crohn's disease (CD) and ulcerative colitis (UC). According to IVW-MR analysis, increased HMGCR expression is associated with a reduced risk of IBD (OR = 0.73, 95% confidence interval (CI) 0.59-0.90, P = 0.003) and CD (OR = 0.75, 95% CI 0.57-0.97, P = 0.03), but not with UC. Additionally, increased NPC1L1 gene expression was associated with elevated risk of IBD (OR = 1.60, 95% CI 1.07-2.40, P = 0.023), but not with CD and UC. However, no significant causal relationships were found between PCSK9 gene expression and IBD, CD, and UC. The sensitivity analysis demonstrated no evidence of heterogeneity or pleiotropy among the reported results.ConclusionsThe heightened expression of genetic variations in HMGCR inhibitor targets could potentially reduce the risk of IBD and CD, while genetic variation in the expression of NPC1L1 targets was positively associated with IBD.
| S-EPMC10775535 | biostudies-literature