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Mediation effect of herpes zoster derived by statin use on cardiovascular disease risk.

ABSTRACT: BACKGROUND/AIMS:Although statins are widely used to reduce the risk of cardiovascular disease (CVD) including stroke and myocardial infarction (MI), it is reported that statin use increases the incidence of herpes zoster (HZ) that is associated with increased risk of CVD. So, we evaluated the mediation effect of HZ caused by statin use on CVD. METHODS:We analyzed a prospective cohort from the National Health Insurance Service-database of South Korea. All individuals received a medical check-up and were followed-up from 2002 to 2013. RESULTS:A total of 275,382 individuals > 40 years old were followed up for 11 years from 2003. Of these, 11,415 people (4%) were classified as statin users and 263,967 (96%) as non-statin users. Those who used statins had significantly lower risks of cardiovascular events, stroke, and MI compared with non-statin users; the adjusted hazard ratios in the multivariate analysis were 0.90 (95% confidence interval [CI], 0.82 to 0.98), 0.88 (95% CI, 0.80 to 0.98), and 0.91 (95% CI, 0.79 to 1.07), respectively. When we calculated the mediating effect of cardiovascular events by statin use through HZ, 11.6% of the total beneficial effect of cardiovascular events by statin use was mitigated through the occurrence of HZ caused by statin use. This mediating effect was higher in the younger age group (< 60 years). CONCLUSION:This study showed that statin use reduced CVD by 10%, but the protective effect of statin use against CVD was mitigated by approximately 10% through the development of HZ caused by statin use.

SUBMITTER: Kim SH

PROVIDER: S-EPMC7487315 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Mediation effect of herpes zoster derived by statin use on cardiovascular disease risk.

Kim Sung-Han SH Yun Sung-Cheol SC Khang Young-Ho YH Kim Min-Chul MC Kwon Sun Uck SU Park Gyung-Min GM Cho Young-Rak YR Lee Kwang Min KM Kim Moo Hyun MH

The Korean journal of internal medicine 20200619 5

<h4>Background/aims</h4>Although statins are widely used to reduce the risk of cardiovascular disease (CVD) including stroke and myocardial infarction (MI), it is reported that statin use increases the incidence of herpes zoster (HZ) that is associated with increased risk of CVD. So, we evaluated the mediation effect of HZ caused by statin use on CVD.<h4>Methods</h4>We analyzed a prospective cohort from the National Health Insurance Service-database of South Korea. All individuals received a med ...[more]

PMID: 32550721

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Project description:Randomized controlled trials (RCTs) show that decreases in low-density lipoprotein cholesterol (LDL-C) by the use of statins cause a significant reduction in the development of cardiovascular disease (CVD). However, one of our previous studies showed that, among eight RCTs that investigated the effect of statins vs. a placebo on CVD development, 56-79% of patients had residual CVD risk after the trials. In three RCTs that investigated the effect of a high dose vs. a usual dose of statins on CVD development, 78-87% of patients in the high-dose statin arms still had residual CVD risk. The risk of CVD development remains even when statins are used to strongly reduce LDL-C, and this type of risk is now regarded as statin residual CVD risk. Our study shows that elevated triglyceride (TG) levels, reduced high-density lipoprotein cholesterol (HDL-C), and the existence of obesity/insulin resistance and diabetes may be important metabolic factors that determine statin residual CVD risk. Here, we discuss atherogenic lipoproteins that were not investigated in such RCTs, such as lipoprotein (a) (Lp(a)), remnant lipoproteins, malondialdehyde-modified LDL (MDA-LDL), and small-dense LDL (Sd-LDL). Lp(a) is under strong genetic control by apolipoprotein (a), which is an LPA gene locus. Variations in the LPA gene account for 91% of the variability in the plasma concentration of Lp(a). A meta-analysis showed that genetic variations at the LPA locus are associated with CVD events during statin therapy, independent of the extent of LDL lowering, providing support for exploring strategies targeting circulating concentrations of Lp(a) to reduce CVD events in patients receiving statins. Remnant lipoproteins and small-dense LDL are highly associated with high TG levels, low HDL-C, and obesity/insulin resistance. MDA-LDL is a representative form of oxidized LDL and plays important roles in the formation and development of the primary lesions of atherosclerosis. MDA-LDL levels were higher in CVD patients and diabetic patients than in the control subjects. Furthermore, we demonstrated the atherogenic properties of such lipoproteins and their association with CVD as well as therapeutic approaches.

Project description:BackgroundThe burden of herpes zoster (HZ) is significant worldwide, with millions affected and the incidence rising. Current literature has identified some risk factors for this disease; however, there is yet to be a comprehensive study that pools all evidence to provide estimates of risk. Therefore, the purpose of this study is to identify various risk factors, excluding immunosuppressive medication, that may predispose an individual to developing HZ.MethodsThe literature search was conducted in MEDLINE, EMBASE, and Cochrane Central, yielding case control, cohort, and cross-sectional studies that were pooled from January 1966 to September 2017. Search terms included the following: zoster OR herpe* OR postherpe* OR shingle* AND risk OR immunosupp* OR stress OR trauma OR gender OR ethnicity OR race OR age OR diabetes OR asthma OR chronic obstructive pulmonary disease OR diabetes. Risk ratios (RRs) for key risk factors were calculated via natural logarithms and pooled using random-effects modeling.ResultsFrom a total of 4417 identified studies, 88 were included in analysis (N = 3, 768 691 HZ cases). Immunosuppression through human immunodeficiency virus/acquired immune deficiency syndrome (RR = 3.22; 95% confidence interval [CI], 2.40-4.33) or malignancy (RR = 2.17; 95% CI, 1.86-2.53) significantly increased the risk of HZ compared with controls. Family history was also associated with a greater risk (RR = 2.48; 95% CI, 1.70-3.60), followed by physical trauma (RR = 2.01; 95% CI, 1.39-2.91) and older age (RR = 1.65; 95% CI, 1.37-1.97). A slightly smaller risk was seen those with psychological stress, females, and comorbidities such as diabetes, rheumatoid arthritis, cardiovascular diseases, renal disease, systemic lupus erythematosus, and inflammatory bowel disease compared with controls (RR range, 2.08-1.23). We found that black race had lower rates of HZ development (RR = 0.69; 95% CI, 0.56-0.85).ConclusionsThis study demonstrated a number of risk factors for development of HZ infection. However, many of these characteristics are known well in advance by the patient and clinician and may be used to guide discussions with patients for prevention by vaccination.

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Mediation effect of herpes zoster derived by statin use on cardiovascular disease risk.

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Mediation effect of herpes zoster derived by statin use on cardiovascular disease risk.

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