Cardiovascular Disease Events In Men Research Articles

THU652 Associations Of Testosterone, Dihydrotestosterone, Estradiol And Sex Hormone-binding Globulin With All-cause And Cardiovascular Mortality, And Incident Cardiovascular Events In Men: Individual Participant Data Meta-analyses

Abstract Disclosure: B.B. Yeap: None. R.J. Marriott: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. K. Murray: None. Studies examining associations of circulating sex steroids with mortality risk in men show inconsistent results for testosterone (T), with limited data for dihydrotestosterone (DHT) and estradiol (E2). We aimed to clarify associations of sex steroids, sex hormone-binding globulin (SHBG) and luteinising hormone (LH) with risks of all-cause and cardiovascular disease (CVD) mortality and incident CVD events in men, by conducting individual participant data (IPD) meta-analyses of prospective cohort studies with sex steroids measured using mass spectrometry. The Androgens In Men Study protocol was registered (PROSPERO: CRD42019139668) and published (BMJ Open 2020;10:e034777). A systematic review (completed Dec 2019) identified relevant studies (BMJ Open 2021;11:e048013). IPD were requested. Cox proportional hazards analyses related total T, SHBG, LH, DHT and E2 concentrations to risk of all-cause mortality and CVD deaths, and risk of incident CVD events. Models were adjusted for age and other sociodemographic factors, lifestyle factors, medical conditions and medications. Summary curves and hazard ratios (HRs) with 95% confidence intervals (CIs) were determined using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (24,596 men), with median baseline age 49-76 years and 4-20 years follow-up among studies. Associations of T with all-cause and CVD mortality risk were non-linear. Risk of all-cause mortality increased for men with baseline T concentrations <8.7 nmol/L, and risk of CVD death increased for men with baseline T <5.3 nmol/L. Lower SHBG concentrations were associated with lower risk of all-cause mortality (median Quintile [Q]1 vs Q5 [Q1:Q5], 20.6 vs 68.3 nmol/L; HR=0.85, CI=0.77-0.95), and CVD death (HR=0.81, CI 0.65-1.00). Men with LH >10 IU/L or E2 <5.1 pmol/L had higher all-cause mortality, with no association of LH or E2 with CVD deaths. Associations of DHT with all-cause and CVD mortality risk were non-linear. Men with lower baseline DHT concentrations had higher risk of all-cause mortality (median Q1:Q5, 0.69 vs 2.45 nmol/L; HR=1.19, CI=1.08-1.30) and CVD deaths (HR=1.29, CI=1.03-1.61), with risk increasing for DHT >2.45 nmol/L. Men with baseline DHT concentrations <0.59 nmol/L had increased risk of incident CVD events, no other hormones were associated with this outcome. Our results suggest greater all-cause and CVD mortality risk among men with very low baseline T, higher baseline SHBG, or either lower or very high baseline DHT concentrations. There was greater risk of CVD events among men with very low baseline DHT concentrations. Potential mechanisms by which SHBG and DHT might influence mortality risk in ageing men merit further investigation. Presentation: Thursday, June 15, 2023

Association of fasting plasma glucose trajectory with lifetime risk of cardiovascular disease.

Few studies have used multiple measurements of fasting plasma glucose (FPG) to examine the impact of long-term FPG trajectory patterns on lifetime risk of cardiovascular disease (CVD). We aimed to identify the long-term patterns in FPG trajectories and to estimate the lifetime risk of CVD according to FPG trajectories. Individuals free of CVD at index ages 35 (n = 72,324), 45 (n = 62,049), and 55 (n = 38,113) years were included. FPG concentrations were measured in 2006, 2008, and 2010. The FPG trajectories were identified by latent mixture modeling. The modified Kaplan-Meier method was used to calculate lifetime risk of CVD. We identified five distinct FPG trajectories and named them according to FPG range and changing pattern over time: low-stable, moderate-stable, moderate-increasing, elevated-decreasing, and elevated-stable. At index age 35 years, we documented 3110 CVD events in men during 371,219 person-years of follow-up and 357 CVD events in women during 107,447 person-years of follow-up. Among all participants, the elevated-stable FPG pattern experienced the highest lifetime risk of CVD (44.8%, 95% CI: 37.8-51.9%), low-stable pattern was lowest (24.3%, 95% CI: 23.3-25.2%). At index age 55 years, although the elevated-stable and elevated-decreasing FPG patterns had similar original FPG concentrations, individuals with elevated-decreasing pattern (30.0%, 95% CI: 23.9-36.1%) had approximately one-third less lifetime risk of CVD than those with elevated-stable pattern (43.6%, 95% CI: 31.8-55.3%). FPG trajectories were significantly associated with the lifetime risk of CVD. Both decrease in FPG over time and consistently lower FPG over 4 years were associated with lower lifetime risk of CVD.

PCN194 Prevalence of Major Adverse Cardiac Events (MACE) in Patients with Prostate Cancer (PC) Receiving Androgen Deprivation Therapy (ADT) in the United States

Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) receptor agonists is used to induce castration and prostate cancer (PC) cell death. Studies have shown an association between GnRH agonists and increased cardiovascular disease (CVD) risk; ∼30% of men with PC have known CVD; cardiovascular mortality is the leading cause of death. In 2010, the Federal Drug Administration required new safety information to the labels of GnRH agonists warning of increased risk of CVD events in men receiving these medications for PC. We assessed the occurrence of major adverse cardiovascular events (MACE) and associated healthcare resource utilization (HCRU) in men with PC receiving agonist ADT. Men receiving ADT with ≥2 claims for a diagnosis of PC were identified in the Marketscan Commercial and Medicare Supplemental Database (1/1/2009-12/31/2018). Index date was the first ADT claim; patients had to be continuously enrolled for 12 months pre- and >2 months post-index. The occurrence of MACE (myocardial infarction, cerebrovascular accident, unstable angina, thromboembolism, percutaneous coronary intervention, and/or coronary bypass graft) was assessed over the study period. Post-period all-cause HCRU was evaluated for patients with and without MACE. The study included 41,986 men; mean age was 70.1 (SD:10.3) years, and median duration of follow-up was 22.8 months. A total of 10,402 patients (24.8%) had a MACE during the study period (8.7% pre-index and 20.6% post-index). Patients with a MACE had three times the number of post-index inpatient admissions per-patient-per-month compared to patients without MACE (0.06[SD:0.10] vs. 0.02[0.06], p<0.001). CVD is a known and important risk for patients with PC treated with GnRH agonists; 20% of patients in this analysis had a MACE following ADT. These patients were more likely to be hospitalized than patients without a MACE. Evaluating CVD history and risk in advanced PC patients when selecting treatment could help to reduce MACE and HCRU.

Low-carbohydrate diet and cardiovascular diseases in Iranian population: Tehran Lipid and Glucose Study

Background and aimsStudies indicated that the risk of cardiovascular disease (CVD) in association to greater adherence to low-carbohydrate diet (LCD) differs in various populations. In this study, we aimed to assess the association of LCD score with the risk of CVD events in a prospective population-based study. Methods and resultsCVD-free participants (n = 2188) were recruited from the Tehran Lipid and Glucose Study (2006–2008) and followed for a mean of 6.7 years. Using a valid and reliable 168 item semi-quantitative food frequency questionnaire, the LCD score was determined based on the percentage of energy as carbohydrate, protein, and fat, which ranged from 0 to 12. Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) of CVD across tertiles of LCD score in women and men.Mean ± SD age of participants (44.8% male) was 38.8 ± 13.0 years, and median (25–75, interquartile range) of the LCD score was 6 (4–8) at baseline. During follow-up, 77 (3.5%) new cases of CVD were identified. After adjustment for sex, age, body mass index, physical activity, smoking, energy intake, diabetes, and hypertension, there was no association between the LCD score and risk of CVD outcomes in all participants (HR = 0.93; 95% CI: 0.86–1.02) and women (HR = 1.13; 95% CI: 0.94–1.36); however, the LCD score was associated with an 11% reduced incidence of CVD events in men (HR = 0.89; 95% CI: 0.80–0.98), (P for trend: 0.028). ConclusionFindings showed that higher adherence to LCD may be associated with a lower risk of CVD outcomes in men but not in women.

Longitudinal Algorithms to Estimate Cardiorespiratory Fitness: Associations With Nonfatal Cardiovascular Disease and Disease-Specific Mortality

This study sought to determine the capacity of cardiorespiratory fitness (CRF) algorithms without exercise testing to predict the risk for nonfatal cardiovascular disease (CVD) events and disease-specific mortality. Cardiorespiratory fitness (CRF) is not routinely measured, as it requires trained personnel and specialized equipment. Participants were 43,356 adults (21% women) from the Aerobics Center Longitudinal Study, followed up between 1974 and 2003. Estimated CRF was determined on the basis of sex, age, body mass index, waist circumference, resting heart rate, physical activity level, and smoking status. Actual CRF was measured by a maximal treadmill test. Risk reduction per 1-metabolic equivalent increase, discriminative ability (c statistic), and net reclassification improvement were determined. During a median follow-up of 14.5 years, 1,934 deaths occurred, 627 due to CVD. In a subsample of 18,095 participants, 1,049 cases of nonfatal CVD events were ascertained. After adjustment for potential confounders, both measured and estimated CRF were inversely associated with risks for all-cause mortality, CVD-related mortality and nonfatal CVD events in men, and all-cause mortality and nonfatal CVD events in women. The risk reduction per 1-metabolic equivalent increase ranged from approximately 10% to 20%. Measured CRF had a slightly better discriminative ability (c statistic) than did estimated CRF, and the net reclassification improvement values in measured CRF versus estimated CRF were 12.3% in men (p < 0.05) and 19.8% in women (p < 0.001). These CRF algorithms utilized information routinely collected to obtain an estimate of CRF, which provides a valid indication of health status. In addition to identifying people at risk, this method can provide more appropriate exercise recommendations that reflect initial CRF levels.

N-terminal pro-B-type natriuretic peptide and the prediction of primary cardiovascular events: results from 15-year follow-up of WOSCOPS

AimsTo test whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) was independently associated with, and improved the prediction of, cardiovascular disease (CVD) in a primary prevention cohort.Methods and resultsIn the West of Scotland Coronary Prevention Study (WOSCOPS), a cohort of middle-aged men with hypercholesterolaemia at a moderate risk of CVD, we related the baseline NT-proBNP (geometric mean 28 pg/mL) in 4801 men to the risk of CVD over 15 years during which 1690 experienced CVD events. Taking into account the competing risk of non-CVD death, NT-proBNP was associated with an increased risk of all CVD [HR: 1.17 (95% CI: 1.11–1.23) per standard deviation increase in log NT-proBNP] after adjustment for classical and clinical cardiovascular risk factors plus C-reactive protein. N-terminal pro-B-type natriuretic peptide was more strongly related to the risk of fatal [HR: 1.34 (95% CI: 1.19–1.52)] than non-fatal CVD [HR: 1.17 (95% CI: 1.10–1.24)] (P= 0.022). The addition of NT-proBNP to traditional risk factors improved the C-index (+0.013; P < 0.001). The continuous net reclassification index improved with the addition of NT-proBNP by 19.8% (95% CI: 13.6–25.9%) compared with 9.8% (95% CI: 4.2–15.6%) with the addition of C-reactive protein. N-terminal pro-B-type natriuretic peptide correctly reclassified 14.7% of events, whereas C-reactive protein correctly reclassified 3.4% of events. Results were similar in the 4128 men without evidence of angina, nitrate prescription, minor ECG abnormalities, or prior cerebrovascular disease.ConclusionN-terminal pro-B-type natriuretic peptide predicts CVD events in men without clinical evidence of CHD, angina, or history of stroke, and appears related more strongly to the risk for fatal events. N-terminal pro-B-type natriuretic peptide also provides moderate risk discrimination, in excess of that provided by the measurement of C-reactive protein.Clinical trial registrationWOSCOPS was carried out and completed prior to the requirement for clinical trial registration.

Is it important to measure or reduce C-reactive protein in people at risk of cardiovascular disease?

Systemic and local vascular inflammation is implicated in atherogenesis. High-sensitivity (hs) assays detecting low concentrations of C-reactive protein (CRP) in healthy individuals have delineated associations of this inflammation marker with cardiovascular events years later. A 160 309-person participant level meta-analysis of 54 prospective studies found the relationship between log-CRP concentration and cardiovascular disease (CVD) events to be linear, with a 2.5-fold risk difference in individuals at opposite extremes of the CRP distribution.1 In vitro studies and animal experiments point to potentially atherogenic actions of CRP,2 and statins lower both CRP and low-density lipoprotein cholesterol (LDL-C).3 The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER),4 designed to ‘assess the effect of rosuvastatin on first ever cardiovascular events in apparently healthy men and women who do not qualify for statin therapy due to low levels of LDL-C, but who are at increased cardiovascular risk due to elevated levels of hs-CRP’, was halted because of ‘unequivocal evidence of a reduction in cardiovascular morbidity and mortality among patients who received CRESTOR (rosuvastatin) when compared to placebo’ (http://clinicaltrials.gov/ct2/show/[NCT00239681][1]). Consequently, the US Food and Drug Administration approved an amended license for rosuvastatin for the primary prevention of CVD events in men and women over 50 and 60 years, respectively, with one other risk factor and a CRP concentration of >2 mg/L. Even before the publication of this trial, the estimated 5 million ‘hs-CRP’ tests were being ordered annually in the USA,5 and updated Canadian guidance on CVD prevention6 now recommends the consideration of ‘hs-CRP’ measurement in those at intermediate risk. The 2010 American College of Cardiology Foundation/American Heart Association Guidelines stated that in ‘men 50 years of age or older and women 60 years of age or older with an LDL-C < 130 … [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00239681&atom=%2Fehj%2F33%2F18%2F2258.atom

Combined effects of brachial pulse pressure and sialic acid for risk of cardiovascular events during 40 years of follow-up in 37 843 individuals

Pulse pressure (PP) is a risk marker for cardiovascular disease (CVD) in individuals 50 years and older. Inflammation is suggested to influence atherosclerosis, but could also increase PP. We aimed to examine the combined effects of PP and the inflammatory marker sialic acid, and their independent roles on CVD risk. From a population-based study in Sweden between 1962 and 1965, 18,429 men and 19,414 women at the age of 50 or older were selected and followed for first CVD event until 2005. We investigated the biological interactions between sialic acid and PP. The associations of PP and sialic acid with risk of CVD were calculated by using Cox proportional hazards model. Adjustments were made for conventional risk factors, mean arterial pressure (MAP) and socioeconomic status. The mean age was 59.5 (SD 6.5) years and the number of incident CVD events in men and women were 3641 and 3227, respectively. No biological interaction was seen between PP and sialic acid. In men, the adjusted hazard ratio for PP was 0.92 [95% confidence interval (CI) 0.88-0.96, P < 0.0001) for 1 SD of PP, and 1.09 (95% CI 1.05-1.13, P < 0.0001) for 1 SD of sialic acid. In women, the corresponding figures were 1.02 (95% CI 0.97-1.07, P = 0.48) and 1.09 (95% CI 1.05-1.13, P < 0.0001). Sialic acid but not PP was an independent risk factor for CVD. The risk induced by PP is highly affected by MAP. This suggests that both estimated arterial stiffness and inflammation contribute through different pathways to risk of CVD.

The research on endothelial function in women and men at risk for cardiovascular disease (REWARD) study: methodology

BackgroundEndothelial function has been shown to be a highly sensitive marker for the overall cardiovascular risk of an individual. Furthermore, there is evidence of important sex differences in endothelial function that may underlie the differential presentation of cardiovascular disease (CVD) in women relative to men. As such, measuring endothelial function may have sex-specific prognostic value for the prediction of CVD events, thus improving risk stratification for the overall prediction of CVD in both men and women. The primary objective of this study is to assess the clinical utility of the forearm hyperaemic reactivity (FHR) test (a proxy measure of endothelial function) for the prediction of CVD events in men vs. women using a novel, noninvasive nuclear medicine -based approach. It is hypothesised that: 1) endothelial dysfunction will be a significant predictor of 5-year CVD events independent of baseline stress test results, clinical, demographic, and psychological variables in both men and women; and 2) endothelial dysfunction will be a better predictor of 5-year CVD events in women compared to men.Methods/DesignA total of 1972 patients (812 men and 1160 women) undergoing a dipyridamole stress testing were recruited. Medical history, CVD risk factors, health behaviours, psychological status, and gender identity were assessed via structured interview or self-report questionnaires at baseline. In addition, FHR was assessed, as well as levels of sex hormones via blood draw. Patients will be followed for 5 years to assess major CVD events (cardiac mortality, non-fatal MI, revascularization procedures, and cerebrovascular events).DiscussionThis is the first study to determine the extent and nature of any sex differences in the ability of endothelial function to predict CVD events. We believe the results of this study will provide data that will better inform the choice of diagnostic tests in men and women and bring the quality of risk stratification in women on par with that of men.

A new approach to compare the predictive power of metabolic syndrome defined by a joint interim statement versus its components for incident cardiovascular disease in Middle East Caucasian residents in Tehran

BackgroundMetabolic syndrome (MS) has an increased risk for developing cardiovascular disease (CVD); however, whether the concept of MS, applying the new joint interim statement definition, has a greater impact on...

Cardiorespiratory Fitness is Inversely Associated with Diabetes and Nonfatal CVD in Men with Metabolic Syndrome

The primary clinical outcomes of metabolic syndrome (Metsyn) are cardiovascular disease (CVD) and diabetes mellitus (DM). Cardiorespiratory fitness (CRF) is inversely associated with CVD mortality in men with Metsyn. Whether higher CRF protects against DM and nonfatal CVD events in individuals with Metsyn is unknown. PURPOSE: We examined the prospective association of CRF with incident DM and nonfatal CVD in 4031 men (mean±SD, age = 47±9 years; body mass index (BMI) = 29±4 kg/m2) who completed a medical examination at the Cooper Clinic between 1979–2002. METHODS: At baseline, participants were free of physician diagnosed DM and CVD (myocardial infarction and stroke), had fasting plasma glucose <126 mg/dL, were not taking insulin, and had measured clinical variables that met ATP-III criteria for Metsyn. CRF was denned as thirds of maximal treadmill exercise duration. DM and nonfatal CVD cases were ascertained from mail-back questionnaires administered between 1982 and 2004. We used Cox regression analysis to examine the association between CRF and the study outcomes. RESULTS: During an average follow-up of 8.9±6.1 years, there were 239 (5.9%) cases of DM and 184 (4.6%) cases of CVD. Across incremental thirds of CRF, the age-and examination year adjusted rates (per 10,000 man-years) of DM were 110.0, 67.1, and 35.2; and of CVD were 72.0, 44.6, and 41.8 (linear trend P <0.001 each). After adjusting for age, examination year, smoking, alcohol intake, and family history of DM and CVD, hazard ratios (95% CI) for DM were 1.00 (referent), 0.63 (0.46–0.85), and 0.33 (0.24–0.47), linear trend P <0.001; and for CVD were 1.00 (referent), 0.59(0.41–0.86), and 0.55 (0.39–0.82), linear trend P <0.01. These patterns of association were materially unchanged after further adjustment for abnormal exercise electrocardiogram responses, and baseline risk factor levels, including fasting glucose and BMI. CONCLUSION: CRF is inversely and independently associated with the incidence of DM and nonfatal CVD events in men at high-risk for these outcomes based on the presence of Metsyn. These findings underscore the importance of promoting higher CRF, presumably through greater physical activity, in the management of Metsyn and in the prevention of DM and CVD.

White Blood Cell Count and Cardiovascular Disease

To examine the relation of white blood cell (WBC) count to the development of cardiovascular disease (CVD), including coronary heart disease, stroke, peripheral arterial disease, and cardiac failure. Traditional CVD risk factors, hematocrit, and vital capacity were considered. Prospective cohort analysis with one baseline examination of relevant risk factors and 12 years of follow-up for CVD. A community-based sample (Farmingham Offspring Study) of 1393 men and 1401 women who were free of CVD at the onset of the study and who were between the ages of 30 and 59 years at baseline. Time-dependent multiple variable logistic regression methods were used. There were 180 CVD events in men and 80 in women. The WBC count was correlated most strongly with the number of cigarettes smoked per day, hematocrit, and vital capacity. Among nonsmoking men with WBC counts within the normal range, the age-adjusted WBC count was significantly associated with CVD and coronary heart disease incidence. For each 1.0 x 10(9)/L-cell difference in WBC count, the CVD risk increased 32%. In women, each 1.0 x 10(9)/L-cell increment in WBC count was associated with a 17% increase in CVD risk, but only in smokers, and the relationship was not statistically significant after adjustment for relevant risk factors. The degree of elevation of WBC count within the normal range is a marker for increased risk of CVD that is partially explained by cigarette smoking. Future studies should include differential WBC determinations to assess their association with CVD.