van der Pim Harst

Association between anxiety but not depressive disorders and leukocyte telomere length after 2 years of follow-up in a population-based sample

BACKGROUND Telomere length is considered an emerging marker of biological aging. Depression and anxiety are associated with excess mortality risk but the mechanisms remain obscure. Telomere length might be involved because it is associated with psychological distress and mortality. The aim of this study was to test whether anxiety and depressive disorders predict telomere length over time in a large population-based sample. Method All analyses were performed in a longitudinal study in a general population cohort of 974 participants. The Composite International Diagnostic Interview (CIDI) was used to measure the presence of anxiety and depressive disorders. Telomere length was measured using monochrome multiplex polymerase chain reaction (PCR) at approximately 2 years of follow-up. We used linear multivariable regression models to evaluate the association between anxiety and depressive disorders and telomere length, adjusting for adverse life events, lifestyle factors, educational level and antidepressant use. RESULTS The presence of anxiety disorders predicted shorter telomeres at follow-up (β = -0.073, t = -2.302, p = 0.022). This association was similar after controlling for adverse life events, lifestyle factors, educational level and antidepressant use (β = -0.077, t = -2.144, p = 0.032). No association was found between depressive disorders and shorter telomeres at follow-up (β = 0.010, t = 0.315, p = 0.753). CONCLUSIONS This study found that anxiety disorders predicted shorter telomere length at follow-up in a general population cohort. The association was not explained by adverse life events, lifestyle factors, educational level and antidepressant use. How anxiety disorders might lead to accelerated telomere shortening and whether this might be a mediator explaining the excess mortality risk associated with anxiety deserve further investigation.

Stressful life events and leukocyte telomere attrition in adulthood: a prospective population-based cohort study

BACKGROUND Telomere attrition might be one of the mechanisms through which psychosocial stress leads to somatic disease. To date it is unknown if exposure to adverse life events in adulthood is associated with telomere shortening prospectively. In the current study we investigated whether life events are associated with shortening of telomere length (TL). METHOD Participants were 1094 adults (mean age 53.1, range 33-79 years) from the PREVEND cohort. Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Life events were assessed with an adjusted version of the List of Threatening Events (LTE). TL was measured by monochrome multiplex quantitative PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of recent life events on TL prospectively. Multivariable regression analyses were performed to assess whether the lifetime life events score or the score of life events experienced before the age of 12 predicted TL cross-sectionally. All final models were adjusted for age, sex, body mass index, presence of chronic diseases, frequency of sports, smoking status, and level of education. RESULTS Recent life events significantly predicted telomere attrition prospectively (B = -0.031, p = 0.007). We were not able to demonstrate a significant cross-sectional relationship between the lifetime LTE score and TL. Nor did we find exposure to adverse life events before the age of 12 to be associated with TL in adulthood. CONCLUSIONS Exposure to recent adverse life events in adulthood is associated with telomere attrition prospectively.

Cholesteryl Ester Transfer Protein Polymorphisms, Statin Use, and Their Impact on Cholesterol Levels and Cardiovascular Events

The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high‐density lipoprotein cholesterol (HDLc), low‐density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta‐analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single‐nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta‐analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10–5) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.

High serum erythropoietin levels are related to heart failure development in subjects from the general population with albuminuria

In patients with heart failure (HF), serum erythropoietin (EPO) levels are elevated and associated with disease severity and outcome. Whether endogenous EPO levels are prospectively associated with the development of HF or cardiovascular events in the general population is unknown.

Telomere length and outcomes in ischaemic heart failure

Leucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is associated with clinical outcomes in patients with ischaemic heart failure and whether this association is superior to chronological age as defined by date of birth.

Pharmacogenetics in heart failure

Pharmacotherapy remains the cornerstone in the treatment of heart failure. There is a wide variability in the individuals response to treatment, which is at least partially ascribed to genetic factors. Pharmacogenetics studies the differential clinical effects due to genetic variances. Some effects of the major neurohormonal inhibitors like angiotensin-converting enzyme (ACE)-inhibitors and beta-blockers are importantly modulated by genetic polymorphisms. So far, however, this does not result in standard genetic testing before starting specific therapy. This review discusses several important pharmacogenetic targets. Furthermore, it is argued that new and sophisticated high-throughput genetic screens could be employed to develop pharmacogenetic screening further. Prospective large-scale pharmacogenetic studies are warranted as we believe that they will identify new targets for therapy and specific populations that benefit from specific treatments.Pharmacotherapy remains the cornerstone in the treatment of heart failure. There is a wide variability in the individuals response to treatment, which is at least partially ascribed to genetic factors. Pharmacogenetics studies the differential clinical effects due to genetic variances. Some effects of the major neurohormonal inhibitors like angiotensin-converting enzyme (ACE)-inhibitors and beta-blockers are importantly modulated by genetic polymorphisms. So far, however, this does not result in standard genetic testing before starting specific therapy. This review discusses several important pharmacogenetic targets. Furthermore, it is argued that new and sophisticated high-throughput genetic screens could be employed to develop pharmacogenetic screening further. Prospective large-scale pharmacogenetic studies are warranted as we believe that they will identify new targets for therapy and specific populations that benefit from specific treatments.

Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System

We would like to thank Dr Huzen and colleagues for their suggestion. Indeed, we are conducting …