Hyperparathyroidism in men - morbidity and mortality during 21 years' follow-up.

Hyperparathyroidism (HPT), including normocalcaemic, vitamin D sufficient (Serum (S)-25(OH)D ≥ 50 nmol/L) hyperparathyroidism (nHPT), has increasingly been diagnosed in the last few decades due to the more common use of the serum parathyroid hormone (S-PTH) assay. We investigated if men with HPT had higher morbidity and mortality than men without HPT during 21 years' follow-up.A random population sample of 750 men, all 50 years of age, was examined in 1993. Endpoints were retrieved 21 years later at 71 years of age.Albumin-corrected serum (S) calcium, S-25-hydroxyvitamin D and S-PTH were assessed along with data on cardiovascular risk factors and medication. Outcome data on fractures, stroke, myocardial infarction, cancer and death were retrieved in 2014; 21 years after primary assessment. The prevalence of HPT at 50 years of age was 9.3%; nHPT 2.8%, primary HPT 0.4%, secondary HPT 0.4%, and HPT with vitamin D insufficiency 6%. Fracture rate, myocardial infarction, stroke, cancer and death occurred similarly in men with or without HPT, as well as in men with nHPT as compared with men without calcium/PTH aberrations during 21 years' follow-up. S-PTH was evenly distributed in the univariable analyses for each outcome. Cox regression analyses showed no increase in serious morbidity or in mortality in men with HPT, irrespective of cause, compared with men with normal S-PTH over a 21-year period. None had HPT at a S-25(OH)D level of 100 nmol/L.

Determinants of Stroke in a General Male Population.

Background and Purpose- To further improve preventive strategies against stroke, there is a need for epidemiological long-term studies. The study aimed at a prospective investigation of stroke determinants in the general male population. Methods- During a period of 48 years, from 50 to 98 years of age, a population-based sample of 854 men was followed using repeated medical examinations, lifestyle questionnaires, data from hospital records and the National Cause of Death Register. Results- Determinants of ischemic stroke were atrial fibrillation (hazard ratio [HR], 6.61; 95% CI, 4.47-9.77); mother dead from cardiovascular disease (HR, 1.53; 1.09-2.17); high education (HR, 0.81; 0.69-0.96); and high physical activity level during leisure time (HR, 0.68; 0.50-0.93). For hemorrhagic stroke heart rate (HR, 1.04; 1.01-1.06) and mother dead from stroke (HR, 3.56; 1.43-8.87) constituted an increased risk. Statistically significant determinants for all stroke were atrial fibrillation (HR, 5.34; 3.68-7.75); high diastolic blood pressure (HR, 1.02; 1.01-1.03); high body weight (HR, 0.96; 0.94-0.99); high educational level (HR, 0.79; 0.68-0.92); wide waist circumference (HR, 1.04; 1.01-1.07); smoking (HR, 1.25; 1.06-1.48); mother dead from cerebrovascular disease (HR, 1.43; 1.05-1.94); and diabetes mellitus (HR, 1.65; 1.02-2.68). Of all men diagnosed with atrial fibrillation, 88% had a stroke during follow-up. Conclusions- Atrial fibrillation was by far the strongest determinant of stroke during 48 years of follow-up in a male population sample followed until the age of 98 years. The results warrant improved prophylaxis through intense treatment of modifiable determinants.

Although Coronary Mortality Has Decreased, Rates of Cardiovascular Disease Remain High: 21 Years of Follow-Up Comparing Cohorts of Men Born in 1913 With Men Born in 1943.

BACKGROUND: Despite a decline in mortality rates from cardiovascular disease (CVD) in the past few decades, the burden of CVD in a contemporary population remains inadequately addressed. Therefore, this study was aimed to investigate secular trends in mortality from coronary artery disease and all-cause mortality over 2 decades, by comparing 2 cohorts of men born 30 years apart and evaluate the prediction of the risk of CVD and all-cause death in a contemporary random sample of Swedish men. METHODS AND RESULTS: Two cohorts of randomly selected men born in 1913 (855 men) and 1943 (798 men) were first examined at age 50 in 1963 and 1993, respectively, and followed longitudinally over 21 years. All-cause mortality and coronary artery disease death were lower in 50- to 71-year-old men born in 1943 compared with those born in 1913, with unadjusted hazard ratios of 0.57 (0.45-0.71) and 0.34 (0.22-0.53), respectively. After adjustment for risk factors (smoking, serum cholesterol, hypertension, systolic blood pressure, diabetes mellitus, body mass index, and physical activity), the differences between the cohorts remained significant for coronary artery disease, hazard ratios 0.57 (0.34-0.94), P=0.029, but not for all-cause mortality hazard ratios 0.82 (0.62-1.07), P=0.14. However, the rate of CVD events during follow-up was still high (30.7%) for the men born in 1943. No statistically significant interaction by birth cohort in contribution of risk factors to death was found between 2 cohorts except physical inactivity. CONCLUSIONS: Despite a marked reduction in the rate of coronary artery disease death over the past 30 years, the burden of CVD events and all-cause mortality remains high. Therefore, intensified efforts to modify contributing risk factors are still required.

Secular changes in cardiovascular risk factors in Swedish 50-year-old men over a 50-year period: The study of men born in 1913, 1923, 1933, 1943, 1953 and 1963.

Background During the past decades, declining trends in mean cholesterol levels and smoking have been observed in Western Europe, whereas obesity and a sedentary lifestyle have increased. Simultaneously, there has been a marked decrease in mortality from cardiovascular (CV) diseases. Methods The aim of the study was to determine whether these trends in CV risk factors continued over a period of 50 years. Six systematic or random population samples of 50-year-old men ( n = 3563) living in Gothenburg, Sweden, were investigated between 1963 and 2013. Results During the 50 years, mean body mass index (BMI) at 50 years of age increased by 2 kg/m2, from 24.8 kg/m2 in 1963 to 26.8 kg/m2 in 2013 ( p < 0.001). A decrease in systolic blood pressure of nearly 10 mmHg was observed from 1963 to 1993, but was not sustained through the past two decades. Mean serum cholesterol fell from 6.42 (SD 1.12) mmol/L to 5.34 (SD 0.97) mmol/L. The prevalence of smoking at 50 years of age decreased markedly from 56.1% in 1963 to 11.9% in 2013. The number of participants with a sedentary lifestyle during leisure time decreased until 1993, but has remained unchanged since. In 2013, 50-year-old men had a 6.9-times higher likelihood of lacking CV risk factors than 50-year-old men in 1963 (95% confidence interval (CI): 3.5-13.3, p < 0.001). The odds ratio for having four or more risk factors was only 0.13 (95% CI: 0.062-0.29, p < 0.001). Conclusion Despite increasing body weight, the total CV risk factor burden has decreased in 50-year-old men over the past 50 years.

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Men born in 1913 followed to age 100 years.

OBJECTIVES: To examine causes of death for men above 80 years of age, and health status in centenarians in a cohort of men followed from age 50 years. Factors of importance for survival were studied. DESIGN: A representative sample of men born in 1913 was first examined in 1963 and re-examined at ages 54, 60, 67, 75, 80 and 100 years. RESULTS: Of 973 selected men, 855 (88%) were examined at age 50, and 10 were alive at age 100.Twenty-seven percent lived until 80 years. Cardiovascular disease was the most common cause of death after this age. Dementia was recorded in two of ten men at age 100. Long survival was related to the mothers' high age at death, to non-smoking, high social class at age 50 and high maximum working capacity at age 54 years. At age 100, the seven examined men had low/normal blood pressure. Serum values of troponin T, N-terminal pro-brain natriuretic peptides and C-reactive protein were elevated, but echocardiographic findings were normal. CONCLUSIONS: Ten men experienced their 100th birthday. Survival was related to non-smoking, mothers' high age at death, high social class and previous high physical working capacity. Age-adjusted reference levels for laboratory tests are needed for centenarians.

Perceived health in 50-year-old women and men and the correlation with risk factors, diseases, and symptoms.

BACKGROUND: Population-based study of a random sample of 50-year-old men and women in Gothenburg, Sweden. OBJECTIVE: To examine the determinants of perceived health and the differences between 50-year-old men and women. METHODS: Men and women born in 1953 were examined between 2003 and 2004. Participation rate was 60% among the men and 67% among the women. Questionnaires were used, including one on perceived health that was ranked on a 7-point scale from 1 (excellent) to 7 (very poor). The participants' medical histories were obtained through a questionnaire, and risk factors were measured. RESULTS: Women generally perceived their health as poorer than men. Women experienced more symptoms than men, and most symptoms were more prevalent among women than men. Poor perceived health was strongly related to number of symptoms. In multivariable analyses 5 factors were related to perceived health in both men and women: working full or part time (women OR [odds ratio] = 0.3, men OR = 0.3) and physical activity (women OR = 0.6, men OR = 0.6) had a positive effect, whereas a low level of social activities (women OR = 1.9, men OR = 1.7), still feeling tired after normal hours of sleep (women OR = 4.5, men OR = 4.0), and feeling burned out during the past 12 months (women OR = 2.3, men OR = 3.0) had a negative effect on perceived health. CONCLUSIONS: Women perceive their health as "worse" in comparison with men. Perceived health is a multifaceted condition related to social circumstances, physical activity, various symptoms, and tiredness after normal hours of sleep both in women and men.

Saving lives, money and resources: drug and CABG/PCI use after myocardial infarction in a Swedish record-linkage study.

BACKGROUND: Drug costs are increasing despite the introduction of cheaper generic drugs. The aim of the present study was to analyse the entire costs of hospital care, out-patient care, and the cost of drugs for 16 months following a myocardial infarction (MI) to see to what extent drug costs contribute to the overall costs of care. METHODS: Diagnoses and costs for care as well as mortality data obtained from the Västra Götaland Region, Sweden, and drug costs from the Swedish Board of Health and Welfare, were merged in a computer file. Patients registered from 1 July 2005 to 30 June 2006 were followed from 28 days after an MI, with follow-up until 31 October 2006. RESULTS: Of 4,725 patients, 711 died before the start of the study and 721 during follow-up. Higher age [hazard ratio (HR, 95%CI) = 1.06 (1.05-1.07)], previous MI [HR = 1.31 (1.13-1.53)] and diabetes mellitus [HR = 1.34 (1.13-1.58)] were associated with increased mortality, which decreased with coronary interventions: CABG/PCI [HR = 0.19 (0.14-0.27)]. In a multivariable analysis, mortality was lower for patients taking simvastatin [HR = 0.62 (0.50-0.76)] and clopidogrel [HR = 0.58 (0.46-0.74)]. CONCLUSION: Costs for out-patient care accounted for 25% and drugs for 5% of total costs. If patients not treated with simvastatin or clopidogrel had received these drugs, an additional 154-306 lives might have been saved. Drug costs would be higher, but total costs lower. Thus, even expensive drugs may reduce overall costs.

Prevalence of cardiovascular risk factors and the metabolic syndrome in middle-aged men and women in Gothenburg, Sweden.

BACKGROUND: Random samples of 50-year-old men living in Gothenburg have been examined every 10th year since 1963 with a focus on cardiovascular risk factors. The aims of the study were to acquire up-to-date information about risk factors in the fifth cohort of 50-year-old men and women, to re-examine those who were 50 years of age in 1993, and to analyse the prevalence of the metabolic syndrome (MetSyn) using different definitions. METHODS: A random sample of men and women born in 1953 were examined in 2003-2004 for cardiovascular risk factors. Men born in 1943 and that participated in the examination in 1993 were also invited. Descriptive statistics were calculated. RESULTS: The participation rate among men and women born in 1953 was 60 and 67% respectively. Among men born in 1943, the participation rate was 87%. The prevalence of obesity was from 15 to 17% (body mass index, BMI >or= 30) in the three samples. The prevalence of known diabetes was 4% among the 50-year-old men and 6% among the 60-year-old men, and 2% among the women. Increased fasting plasma glucose varied substantially from 4 to 33% depending on cut-off level and gender. Mean cholesterol was 5.4 to 5.5 mmol/l. Smoking was more common among women aged 50 (26%) than among men aged 50 (22%) and 60 years (15%). The prevalence of the MetSyn varied with the definition used: from 10 to 15.8% among the women, from 16.1 to 26% among 50-year-old men, and from 19.9 to 35% among the 60-year-old men. Only 5% of the men and women had no risk factors. CONCLUSION: This study provides up-to-date information about the prevalence of cardiovascular risk factors and the MetSyn in middle-aged Swedish men and women. Different definitions of the MetSyn create confusion regarding which definition to use.

Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1).

BACKGROUND AND PURPOSE: The NeuroThera Effectiveness and Safety Trial-1 (NEST-1) study evaluated the safety and preliminary effectiveness of the NeuroThera Laser System in the ability to improve 90-day outcomes in ischemic stroke patients treated within 24 hours from stroke onset. The NeuroThera Laser System therapeutic approach involves use of infrared laser technology and has shown significant and sustained beneficial effects in animal models of ischemic stroke. METHODS: This was a prospective, intention-to-treat, multicenter, international, double-blind, trial involving 120 ischemic stroke patients treated, randomized 2:1 ratio, with 79 patients in the active treatment group and 41 in the sham (placebo) control group. Only patients with baseline stroke severity measured by National Institutes of Health Stroke Scale (NIHSS) scores of 7 to 22 were included. Patients who received tissue plasminogen activator were excluded. Outcome measures were the patients' scores on the NIHSS, modified Rankin Scale (mRS), Barthel Index, and Glasgow Outcome Scale at 90 days after treatment. The primary outcome measure, prospectively identified, was successful treatment, documented by NIHSS. This was defined as a complete recovery at day 90 (NIHSS 0 to 1), or a decrease in NIHSS score of at least 9 points (day 90 versus baseline), and was tested as a binary measure (bNIH). Secondary outcome measures included mRS, Barthel Index, and Glasgow Outcome Scale. Primary statistical analyses were performed with the Cochran-Mantel-Haenszel rank test, stratified by baseline NIHSS score or by time to treatment for the bNIH and mRS. Logistic regression analyses were conducted to confirm the results. RESULTS: Mean time to treatment was >16 hours (median time to treatment 18 hours for active and 17 hours for control). Time to treatment ranged from 2 to 24 hours. More patients (70%) in the active treatment group had successful outcomes than did controls (51%), as measured prospectively on the bNIH (P=0.035 stratified by severity and time to treatment; P=0.048 stratified only by severity). Similarly, more patients (59%) had successful outcomes than did controls (44%) as measured at 90 days as a binary mRS score of 0 to 2 (P=0.034 stratified by severity and time to treatment; P=0.043 stratified only by severity). Also, more patients in the active treatment group had successful outcomes than controls as measured by the change in mean NIHSS score from baseline to 90 days (P=0.021 stratified by time to treatment) and the full mRS ("shift in Rankin") score (P=0.020 stratified by severity and time to treatment; P=0.026 stratified only by severity). The prevalence odds ratio for bNIH was 1.40 (95% CI, 1.01 to 1.93) and for binary mRS was 1.38 (95% CI, 1.03 to 1.83), controlling for baseline severity. Similar results held for the Barthel Index and Glasgow Outcome Scale. Mortality rates and serious adverse events (SAEs) did not differ significantly (8.9% and 25.3% for active 9.8% and 36.6% for control, respectively, for mortality and SAEs). CONCLUSIONS: The NEST-1 study indicates that infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety and effectiveness is warranted.

The prognosis for individuals on disability retirement. An 18-year mortality follow-up study of 6887 men and women sampled from the general population.

BACKGROUND: Several studies have shown a markedly higher mortality rate among disability pensioners than among non-retired. Since most disability pensions are granted because of non-fatal diseases the reason for the increased mortality therefore remains largely unknown. The aim of this study was to evaluate potential explanatory factors. METHODS: Data from five longitudinal cohort studies in Sweden, including 6,887 men and women less than 65 years old at baseline were linked to disability pension data, hospital admission data, and mortality data from 1971 until 2001. Mortality odds ratios were analyzed with Poisson regression and Cox's proportional hazards regression models. RESULTS: 1,683 (24.4%) subjects had a disability pension at baseline or received one during follow up. 525 (7.6%) subjects died during follow up. The subjects on disability pension had a higher mortality rate than the non-retired, the hazards ratio (HR) being 2.78 (95%CI 2.08-3.71) among women and 3.43 (95%CI 2.61-4.51) among men. HR was highest among individuals granted a disability pension at young ages (HR >7), and declined parallel to age at which the disability pension was granted. The higher mortality rate among the retired subjects was not explained by disability pension cause or underlying disease or differences in age, marital status, educational level, smoking habits or drug abuse. There was no significant association between reason for disability pension and cause of death. CONCLUSION: Subjects with a disability pension had increased mortality rates as compared with non-retired subjects, only modestly affected by adjustments for psycho-socio-economic factors, underlying disease, etcetera. It is unlikely that these factors were the causes of the unfavorable outcome. Other factors must be at work.

Insulin resistance and other risk factors for coronary heart disease in elderly men. The Study of Men Born in 1913 and 1923.

BACKGROUND: We have previously shown that insulin is not a major risk factor for CHD. Our data have been re-analysed with longer follow-up and the homeostasis model assessment (HOMA) method. DESIGN: Prospective cohort study of 57- and 67-year-old men. METHODS: Insulin resistance was estimated with the HOMA equation. Standard methods were used to measure risk factors. The endpoint (CHD) was the combination of non-fatal myocardial infarction and fatal CHD during 13 years of follow-up. RESULTS: The risk of CHD increased 2.5-fold in known diabetics compared with those with normal glucose tolerance, 2.2-fold among those in the highest compared with the lowest quintile of insulin resistance, and 2.4-fold among those in the highest compared with the lowest quintile of fasting insulin. Increased physical activity decreased the risk of CHD by 65%. Cholesterol was also a significant risk factor for CHD but blood pressure, obesity and smoking were not related to the incidence of CHD. CONCLUSION: Insulin resistance is a significant risk factor for CHD. Whether it is a causal risk factor remains to be proven. Regular physical activity protects against CHD.

Ximelagatran and melagatran compared with dalteparin for prevention of venous thromboembolism after total hip or knee replacement: the METHRO II randomised trial.

BACKGROUND: Heparins substantially reduce the risk of thromboembolic complications after total hip or knee replacement. However, they can be given only by injection and have several other drawbacks. We did a multicentre, randomised, double-blind study to examine the dose-response relation of subcutaneous melagatran, a direct thrombin inhibitor, followed by oral ximelagatran as thromboprophylaxis after total hip or knee replacement. We aimed to compare the efficacy and safety with that of dalteparin. METHODS: Of 1900 patients, 1495 were assigned to four dose categories of subcutaneous melagatran from just before surgery (1.00 mg, 1.50 mg, 2.25 mg, or 3.00 mg twice daily) followed from the day after surgery by oral ximelagatran (8 mg, 12 mg, 18 mg, or 24 mg twice daily). 381 patients were assigned subcutaneous dalteparin 5000 IU once daily, from the evening before surgery. Bilateral venography was done at 7-10 days, and clinically suspected venous thromboembolism (VTE) was confirmed radiologically. The primary endpoint was the rate of deep-vein thrombosis and pulmonary embolism (PE). Analyses were by intention to treat. FINDINGS: 1876 patients underwent total replacement of hip (n=1270) or knee (n=606); evaluable venograms were obtained in 1473 (79%). Four patients without evaluable venograms had PE. Overall, a significant dose-dependent decrease in VTE was seen with melagatran/ximelagatran (lowest to highest group: 111 [37.8%], 70 [24.1%], 71 [23.7%], and 43 [15.1%]; p=0.0001); there were also significant relations for both total hip and total knee replacement individually. The frequency of VTE was significantly lower with the highest dose of melagatran/ximelagatran than with dalteparin (15.1% vs 28.2%, p<0.0001). There were no reoperations due to bleeding and no critical organ bleeding. Excessive surgical bleeding was uncommon but more frequent in the highest dose group. INTERPRETATION: This sequential therapy was effective and safe in patients undergoing major joint replacement surgery. The findings should be confirmed in a large phase III trial.