Male childlessness as independent predictor of risk of cardiovascular and all-cause mortality: A population-based cohort study with more than 30 years follow-up

Abstract

In a recent population-based study, an elevated risk of the Metabolic syndrome (MetS) and type 2 diabetes was found in childless men compared to those who have fathered one or more children. Therefore, by using a larger cohort of more than 22 000 men from the Malmo Preventive Project (MPP) we aimed to expand our observations in order to evaluate the metabolic profile of childless men and to evaluate if childlessness is an additional and independent predictor of major adverse cardiovascular events (MACE), mortality and incident diabetes when accounting for well-known biochemical, anthropometric, socioeconomic and lifestyle related known risk factors. Logistic regression was used to assess risk of MACE, diabetes and MetS at baseline. Multivariate Cox regression was used to evaluate the risks of MACE and mortality following the men from baseline screening until first episode of MACE, death from other causes, emigration, or end of follow-up (31 st December 2016) adjusting for age, family history, marital status, smoking, alcohol consumption, educational status, body mass index, prevalent diabetes, high blood lipids, increased fasting glucose and hypertension. Childless men presented with a worse metabolic profile than fathers at the baseline examination, with elevated risk of high triglycerides, odds ratio (OR) 1.24 (95% CI: 1.10-1.42), high fasting glucose OR 1.23 (95%CI: 1.05-1.43) and high blood pressure, OR 1.28 (95%CI: 1.14-1.45), respectively. In the fully adjusted prospective analysis, childless men presented with elevated risk of cardiovascular mortality, HR: 1.33 (95% CI: 1.18-1.49) and all-cause mortality, HR 1.23 (95%CI: 1.14-1.33), respectively. In conclusion, these results add to previous studies showing associations between male reproductive health, morbidity and mortality. Male childlessness, independently of well-known socioeconomic , behavioral and metabolic risk factors, predicts risk of cardiovascular disease and

Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality

“…In the current study we used a similar cohort from the same region of southern Sweden which provided genetic data and was specifically designed to study CVD risk. We were able to show the same effect of paternal status on CVD mortality estimates as previously published 2 . To the best of our knowledge this is the first study which evaluates the impact of established genetic risk scores for CVD on the association between parental status and the risk of CAD and CVD mortality.…”

“…Previously, by using data from a prospective cohort of 22,000 men with long follow-up from the same urban population, we were able to show that childlessness can be regarded as an independent risk marker for CVD along with other well-known risk factors 2 , an association previously reported by other authors 4 , 26 – 28 . In the current study we used a similar cohort from the same region of southern Sweden which provided genetic data and was specifically designed to study CVD risk.…”

“…For this purpose, we used data from a population-based study, specifically designed to study the epidemiology of CVD, among middle-aged men from Sweden using information on paternal status in late mid-life as a fertility proxy. Childless men have already been shown to be at higher risk for CVD and associated mortality in a similar cohort from the same population 2 .…”

“…Poor semen quality is a laboratory marker of impaired male fertility, whereas in the clinical setting, lack of signs of female reproductive dysfunction is regarded as an indicator of male contribution to a couple’s infertility. In an epidemiological context, male childlessness is often used as proxy for male infertility 2 – 5 .…”

“…In a population-based register study, more frequent prescription of drugs used for the treatment of hypertension, dyslipidemia, and MetS was found in men who fathered children following intracytoplasmic sperm injection (ICSI), the preferred method of symptomatic treatment of infertility associated with poor semen quality 10 , as compared to those who became fathers without assisted reproduction. Married, childless men, were reported to have a higher risk of cardiovascular disease (CVD), type 2 diabetes 3 , 4 and death caused by CVD 2 . Therefore, a man’s reproductive potential has been suggested to be a marker of general health 9 .…”