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      Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study

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          Abstract

          In a prospective Australian population-based study linking questionnaire data from 2006–2009 with hospitalisation and death data to June 2010 for 95,038 men aged ≥45 years, Banks and colleagues found that more severe erectile dysfunction was associated with higher risk of cardiovascular disease.

          Abstract

          Background

          Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes.

          Methods and Findings

          We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2.26), atrioventricular and left bundle branch block (6.62, 1.86–23.56), and (peripheral) atherosclerosis (2.47, 1.18–5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16–2.35) and intracerebral haemorrhage (0.78, 0.20–2.97).

          Conclusions

          These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.

          Please see later in the article for the Editors' Summary

          Editors' Summary

          Background

          Erectile dysfunction is the medical term used when a man is unable to achieve or sustain an erection of his penis suitable for sexual intercourse. Although a sensitive topic that can cause much embarrassment and distress, erectile dysfunction is very common, with an estimated 40% of men over the age of 40 years experiencing frequent or occasional difficulties. The most common causes of erectile dysfunction are medications, chronic illnesses such as diabetes, and drinking too much alcohol. Stress and mental health problems can also cause or worsen erectile dysfunction. There is also increasing evidence that erectile dysfunction may actually be a symptom of cardiovascular disease—a leading cause of death worldwide—as erectile dysfunction could indicate a problem with blood vessels or poor blood flow commonly associated with cardiovascular disease.

          Why Was This Study Done?

          Although previous studies have suggested that erectile dysfunction can serve as a marker for cardiovascular disease in men not previously diagnosed with the condition, few studies to date have investigated whether erectile dysfunction could also indicate worsening disease in men already diagnosed with cardiovascular disease. In addition, previous studies have typically been small and have not graded the severity of erectile dysfunction or investigated the specific types of cardiovascular disease associated with erectile dysfunction. In this large study conducted in Australia, the researchers investigated the relationship of the severity of erectile dysfunction with a range of cardiovascular disease outcomes among men with and without a previous diagnosis of cardiovascular disease.

          What Did the Researchers Do and Find?

          The researchers used information from the established 45 and Up Study, a large cohort study that includes 123,775 men aged 45 and over, selected at random from the general population of New South Wales, a large region of Australia. A total of 95,038 men were included in this analysis. The male participants completed a postal questionnaire that included a question on erectile functioning, which allowed the researchers to define erectile dysfunction as none, mild, moderate, or severe. Using information captured in the New South Wales Admitted Patient Data Collection—a complete record of all public and private hospital admissions, including the reasons for admission and the clinical diagnosis—and the government death register, the researchers were able to determine health outcomes of all study participants. They then used a statistical model to estimate hospital admissions for cardiovascular disease events for different levels of erectile dysfunction.

          The researchers found that the rates of severe erectile dysfunction among study participants were 2.2% for men aged 45–54 years, 6.8% for men aged 55–64 years, 20.2% for men aged 65–74 years, 50.0% for men aged 75–84 years, and 75.4% for men aged 85 years and over. During the study period, the researchers recorded 7,855 hospital admissions related to cardiovascular disease and 2,304 deaths. The researchers found that among men without previous cardiovascular disease, those with severe erectile dysfunction were more likely to develop ischemic heart disease (risk 1.60), heart failure (risk 8.00), peripheral vascular disease (risk 1.92), and other causes of cardiovascular disease (risk 1.26) than men without erectile dysfunction. The risks of heart attacks and heart conduction problems were also increased (1.66 and 6.62, respectively). Furthermore, the combined risk of all cardiovascular disease outcomes was 1.35, and the overall risk of death was also higher (risk 1.93) in these men. The researchers found that these increased risks were similar in men with erectile dysfunction who had previously been diagnosed with cardiovascular disease.

          What Do These Findings Mean?

          These findings suggest that compared to men without erectile dysfunction, there is an increasing risk of ischemic heart disease, peripheral vascular disease, and death from all causes in those with increasing degrees of severity of erectile dysfunction. The authors emphasize that erectile dysfunction is a risk marker for cardiovascular disease, not a risk factor that causes cardiovascular disease. These findings add to previous studies and highlight the need to consider erectile dysfunction in relation to the risk of different types of cardiovascular disease, including heart failure and heart conduction disorders. However, the study's reliance on the answer to a single self-assessed question on erectile functioning limits the findings. Nevertheless, these findings provide useful information for clinicians: men with erectile dysfunction are at higher risk of cardiovascular disease, and the worse the erectile dysfunction, the higher the risk of cardiovascular disease. Men with erectile dysfunction, even at mild or moderate levels, should be screened and treated for cardiovascular disease accordingly.

          Additional Information

          Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001372.

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          Most cited references23

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          Investigation of relative risk estimates from studies of the same population with contrasting response rates and designs

          Background There is little empirical evidence regarding the generalisability of relative risk estimates from studies which have relatively low response rates or are of limited representativeness. The aim of this study was to investigate variation in exposure-outcome relationships in studies of the same population with different response rates and designs by comparing estimates from the 45 and Up Study, a population-based cohort study (self-administered postal questionnaire, response rate 18%), and the New South Wales Population Health Survey (PHS) (computer-assisted telephone interview, response rate ~60%). Methods Logistic regression analysis of questionnaire data from 45 and Up Study participants (n = 101,812) and 2006/2007 PHS participants (n = 14,796) was used to calculate prevalence estimates and odds ratios (ORs) for comparable variables, adjusting for age, sex and remoteness. ORs were compared using Wald tests modelling each study separately, with and without sampling weights. Results Prevalence of some outcomes (smoking, private health insurance, diabetes, hypertension, asthma) varied between the two studies. For highly comparable questionnaire items, exposure-outcome relationship patterns were almost identical between the studies and ORs for eight of the ten relationships examined did not differ significantly. For questionnaire items that were only moderately comparable, the nature of the observed relationships did not differ materially between the two studies, although many ORs differed significantly. Conclusions These findings show that for a broad range of risk factors, two studies of the same population with varying response rate, sampling frame and mode of questionnaire administration yielded consistent estimates of exposure-outcome relationships. However, ORs varied between the studies where they did not use identical questionnaire items.
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            Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force.

            Traditional risk factors do not explain all of the risk for incident coronary heart disease (CHD) events. Various new or emerging risk factors have the potential to improve global risk assessment for CHD. To summarize the results of 9 systematic reviews of novel risk factors to help the U.S. Preventive Services Task Force (USPSTF) evaluate the factors' clinical usefulness. Results from a MEDLINE search for English-language articles published from 1966 to September 2008, using the Medical Subject Heading terms cohort studies and cardiovascular diseases in combination with terms for each risk factor. Studies were included if the participants had no baseline cardiovascular disease and the investigators adjusted for at least 6 Framingham risk factors. Study quality was evaluated by using USPSTF criteria and overall quality of evidence for each risk factor by using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation framework. Each factor's potential clinical value was evaluated by using a set of criteria that emphasized the importance of the effect of that factor on the reclassification of intermediate-risk persons. 9 systematic reviews were conducted. C-reactive protein (CRP) was the best candidate for use in screening and the most rigorously studied, but evidence that changes in CRP level lead to primary prevention of CHD events is inconclusive. The other evaluated risk factors were coronary artery calcium score as measured by electron-beam computed tomography, lipoprotein(a) level, homocysteine level, leukocyte count, fasting blood glucose, periodontal disease, ankle-brachial index, and carotid intima-media thickness. The availability and validity of the evidence varied considerably across the risk factors in terms of aggregate quality, consistency of findings, and applicability to intermediate-risk persons in the general population. For most risk factors, no studies assessed their usefulness for reclassifying intermediate-risk persons. Because of lack of access to original data, no firm conclusions could be drawn about differences in risk prediction among racial and ethnic groups. The review did not emphasize within-cohort comparisons of multiple risk factors. The current evidence does not support the routine use of any of the 9 risk factors for further risk stratification of intermediate-risk persons.
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              Validity of self-reported height and weight and derived body mass index in middle-aged and elderly individuals in Australia.

              Body mass index (BMI) is an important measure of adiposity. While BMI derived from self-reported data generally agrees well with that derived from measured values, evidence from Australia is limited, particularly for the elderly. We compared self-reported with measured height and weight in a random sample of 608 individuals aged ≥ 45 from the 45 and Up Study, an Australian population-based cohort study. We assessed degree of agreement and correlation between measures, and calculated sensitivity and specificity to quantify BMI category misclassification. On average, in males and females respectively, height was overestimated by 1.24 cm (95% CI: 0.75-1.72) and 0.59 cm (0.26-0.92); weight was underestimated by 1.68 kg (-1.99- -1.36) and 1.02 kg (-1.24- -0.80); and BMI based on self-reported measures was underestimated by 0.90 kg/m2 (-1.09- -0.70) and 0.60 kg/m2 (-0.75- -0.45). Underestimation increased with increasing measured BMI. There were strong correlations between self-reported and measured height, weight and BMI (r=0.95, 0.99 and 0.95, respectively, p<0.001). While there was excellent agreement between BMI categories from self-reported and measured data (kappa=0.80), obesity prevalence was underestimated. Findings did not differ substantially between middle-aged and elderly participants. Self-reported data on height and weight quantify body size appropriately in middle-aged and elderly individuals for relative measures, such as quantiles of BMI. However, caution is necessary when reporting on absolute BMI and standard BMI categories, based on self-reported data, particularly since use of such data is likely to result in underestimation of the prevalence of obesity. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                PLoS
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                January 2013
                January 2013
                29 January 2013
                : 10
                : 1
                : e1001372
                Affiliations
                [1 ]National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australian Capital Territory, Australia
                [2 ]The Sax Institute, Sydney, New South Wales, Australia
                [3 ]College of Medicine, Biology and the Environment, Australian National University, Canberra, Australian Capital Territory, Australia
                [4 ]Concord Repatriation General Hospital, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
                [5 ]Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia
                [6 ]The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia
                London School of Hygiene & Tropical Medicine, United Kingdom
                Author notes

                JC has received research grants from Servier, administered through the University of Sydney and The George Institute, as principal investigator for the ADVANCE trial and ADVANCE-ON post trial follow-up study, and have received honoraria from Servier for speaking about ADVANCE at Scientific meetings. PM has received payment from Pfizer for giving a lecture on the treatment of pulmonary hypertension. All other authors have declared that no competing interests exist.

                Conceived and designed the experiments: EB GJ JPC WA LK PSM. Analyzed the data: GJ. Wrote the first draft of the manuscript: EB GJ. Contributed to the writing of the manuscript: EB GJ WA LK PSM RK JPC. ICMJE criteria for authorship read and met: EB GJ WA LK PSM RK JPC. Agree with manuscript results and conclusions: EB GJ WPA LK PSM RK JPC.

                Article
                PMEDICINE-D-12-01783
                10.1371/journal.pmed.1001372
                3558249
                23382654
                59427c5e-ac39-4c96-a284-bc154d196ee8
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 June 2012
                : 4 December 2012
                Page count
                Pages: 13
                Funding
                This specific project was supported by a development grant from the National Heart Foundation, NSW Cardiovascular Research Network, made available through the 45 and Up Study Cardiovascular Research Collaboration. EB is supported by the Australian National Health and Medical Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
                Categories
                Research Article
                Medicine
                Cardiovascular
                Epidemiology
                Cardiovascular Disease Epidemiology
                Urology
                Sexual Dysfunction

                Medicine
                Medicine

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