The possible role of the vasopressin system in hematopoiesis.

Vasopressin is a pleiotropic hormone that controls body fluid homeostasis. Vasopressin has also been proposed to be involved in erythropoiesis, thrombocyte activity and inflammation. However, whether increasing vasopressin is associated with changes in hematopoietic markers is not known. To evaluate this gap of knowledge we measured the vasopressin marker copeptin and markers of erythropoiesis (erythrocyte count, hemoglobin (Hb), red blood cell distribution width (RDW), mean corpuscular volume (MCV), erythrocyte volume fraction (EVF)), leukocyte count (total count, lymphocytes, neutrophils) and thrombocyte count in 5312 participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS). The associations between increasing copeptin tertile and the hematopoietic markers were analyzed in multivariate linear regression analyses. We found that increasing copeptin tertile was significantly (p < 0.001) associated with increasing erythrocytes, RDW, EVF, Hb, leukocytes and neutrophils after adjustment for age, sex, current smoking, prevalent diabetes, hypertension, creatinine, body mass index and physical activity. Increasing copeptin tertile was, however, not associated with change in MCV, lymphocyte or thrombocyte count. In conclusion, we found that increasing copeptin levels are positively associated with markers of erythropoiesis and leukocyte count in the general population. These results warrant further research on possible mechanistic effects of vasopressin on hematopoiesis.

Copeptin as a predictive marker of incident heart failure.

AIMS: Heart failure (HF) is a common disease with increasing prevalence and poor prognosis. The vasopressin (VP) marker copeptin predicts development of diabetes mellitus, diabetic heart disease, coronary artery disease, and premature mortality. Copeptin is elevated in HF patients and predicts a worse outcome. This study aims to investigate whether copeptin can predict HF development. METHODS: Copeptin was analysed in 5297 individuals (69.6% men) without prevalent HF from the Malmö Preventive Project, a population-based prospective cohort. Cox proportional hazards models were used to analyse risk of incident HF by copeptin levels after adjusting for conventional cardiovascular risk factors. RESULTS: During a median follow-up time of 11.1 years, 350 subjects (6.6%) were diagnosed with HF. Of these events, 99 were classified as myocardial infarction (MI) related HF and 251 as non-MI-related HF. Individuals in the top quartile of copeptin had, after multivariate adjustment for conventional risk factors (age, sex, systolic blood pressure, diabetes mellitus, body mass index, antihypertensive therapy, smoking, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), a significantly increased risk of developing HF by 1.63 [confidence interval (CI) 1.20-2.21] for HF compared with the reference quartile 1. After adjustment for conventional risk factors, the hazard ratio (HR) per standard deviation increase of log-transformed copeptin for any HF was 1.30 (95% CI 1.17-1.46), whereas it was 1.39 (CI 1.13-1.71) for MI-related HF and 1.26 (CI 1.11-1.44) for non-MI-related HF. The associations remained after additional adjustment for estimated glomerular filtration rate [HR 1.24 (95% CI: 1.10-1.40)] and for pro atrial natriuretic peptide on top of conventional risk factors [HR 1.14 (95% CI: 1.02-1.28)]. CONCLUSIONS: Elevated copeptin predicts development of HF in older adults. Copeptin is a risk marker of VP-driven HF susceptibility and a candidate to guide prevention efforts of HF targeting the VP system.

Smoking and Alcohol Intake but Not Muscle Strength in Young Men Increase Fracture Risk at Middle Age: A Cohort Study Linked to the Swedish National Patient Registry.

We aimed to determine the relationship between handgrip strength, smoking, and alcohol consumption in young men and fracture risk at middle age. Thus, we carried out a cohort study including young men undergoing conscription examination in Sweden from September 1969 to May 1970 at a typical age of 18 years. Data on muscle strength, height, weight, and lifestyle factors were linked to the National Patient Register 1987-2010. Handgrip strength was considered the main exposure and smoking and alcohol consumption as secondary exposures. Outcomes were all fractures (except face, skull, digits), major osteoporotic fractures (thoracic/lumbar spine, proximal humerus, distal forearm or hip), and major traumatic fractures (shaft of humerus, forearm, femur, or lower leg) based on ICD-9 and -10 codes. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) according to handgrip strength as a continuous variable (per 1 SD), after adjustment for weight, height, parental education, smoking, and alcohol consumption. A total of 40,112 men were included, contributing 892,572 person-years. Overall, 3974 men fractured in middle age with the incidence rate (95% CI) of 44.5 (43.2-45.9) per 1000 person-years. The corresponding rates were12.2 and 5.6 per 1000 person-years for major osteoporotic and traumatic fractures, respectively. Handgrip strength-adjusted HR (95% CI) was 1.01 (0.98-1.05), 0.94 (0.88-1.00), and 0.98 (0.88-1.08) per SD for all, major osteoporotic, and major traumatic fractures, respectively. Adjusted HR (95% CI) for smokers (>21 cigarettes/d) was 1.44 (1.21, 1.71) for all fractures, while the association between alcohol consumption and hazards of fracture was J-shaped. Therefore, young adult handgrip strength was not associated with fracture risk in middle-age men, although smoking and high alcohol consumption did confer an increased risk. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Does pregnancy complication history improve cardiovascular disease risk prediction? Findings from the HUNT study in Norway.

AIM: To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD). METHODS AND RESULTS: This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of Death Registry. Using an established CVD risk prediction model (NORRISK 2), we predicted 10-year risk of CVD (non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and HDL-cholesterol, smoking, anti-hypertensives, and family history of myocardial infarction). We evaluated whether adding pregnancy complication history improved model fit, calibration, discrimination, and reclassification. Among 18 231 women who were parous, ≥40 years of age, and CVD-free at start of follow-up, 39% had any pregnancy complication history and 5% experienced a CVD event during a median follow-up of 8.2 years. While pre-eclampsia and SGA were associated with CVD in unadjusted models (HR 1.96, 95% CI 1.44-2.65 for pre-eclampsia and HR 1.46, 95% CI 1.18-1.81 for SGA), only pre-eclampsia remained associated with CVD after adjusting for established risk factors (HR 1.60, 95% CI 1.16-2.17). Adding pregnancy complication history to the established prediction model led to small improvements in discrimination (C-index difference 0.004, 95% CI 0.002-0.006) and reclassification (net reclassification improvement 0.02, 95% CI 0.002-0.05). CONCLUSION: Pre-eclampsia independently predicted CVD after controlling for established risk factors; however, adding pre-eclampsia, gestational hypertension, preterm delivery, and SGA made only small improvements to CVD prediction among this representative sample of parous Norwegian women.

Lifestyle in progression from hypertensive disorders of pregnancy to chronic hypertension in Nurses' Health Study II: observational cohort study.

Objectives To study the association between lifestyle risk factors and chronic hypertension by history of hypertensive disorders of pregnancy (HDP: gestational hypertension and pre-eclampsia) and investigate the extent to which these risk factors modify the association between HDP and chronic hypertension.Design Prospective cohort study.Setting Nurses' Health Study II (1991-2013).Participants 54 588 parous women aged 32 to 59 years with data on reproductive history and without previous chronic hypertension, stroke, or myocardial infarction.Main outcome measure Chronic hypertension diagnosed by a physician and indicated through nurse participant self report. Multivariable Cox proportional hazards models were used to investigate the development of chronic hypertension contingent on history of HDP and four lifestyle risk factors: post-pregnancy body mass index, physical activity, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, and dietary sodium/potassium intake. Potential effect modification (interaction) between each lifestyle factor and previous HDP was evaluated with the relative excess risk due to interaction.Results 10% (n=5520) of women had a history of HDP at baseline. 13 971 cases of chronic hypertension occurred during 689 988 person years of follow-up. Being overweight or obese was the only lifestyle factor consistently associated with higher risk of chronic hypertension. Higher body mass index, in particular, also increased the risk of chronic hypertension associated with history of HDP (relative excess risk due to interaction P<0.01 for all age strata). For example, in women aged 40-49 years with previous HDP and obesity class I (body mass index 30.0-34.9), 25% (95% confidence interval 12% to 37%) of the risk of chronic hypertension was attributable to a potential effect of obesity that was specific to women with previous HDP. There was no clear evidence of effect modification by physical activity, DASH diet, or sodium/potassium intake on the association between HDP and chronic hypertension.Conclusion This study suggests that the risk of chronic hypertension after HDP might be markedly reduced by adherence to a beneficial lifestyle. Compared with women without a history of HDP, keeping a healthy weight seems to be especially important with such a history.

Knee extensor strength and body weight in adolescent men and the risk of knee osteoarthritis by middle age.

OBJECTIVES: To assess the extent to which knee extensor strength and weight in adolescence are associated with knee osteoarthritis (OA) by middle age. METHODS: We studied a cohort of 40 121 men who at age 18 years in 1969/1970 underwent mandatory conscription in Sweden. We retrieved data on isometric knee extensor strength, weight, height, smoking, alcohol consumption, parental education and adult occupation from Swedish registries. We identified participants diagnosed with knee OA or knee injury from 1987 to 2010 through the National Patient Register. We estimated the HR of knee OA using multivariable-adjusted Cox proportional regression model. To assess the influence of adult knee injury and occupation, we performed a formal mediation analysis. RESULTS: The mean (SD) knee extensor strength was 234 (47) Nm, the mean (SD) weight was 66 (9.3) kg. During 24 years (median) of follow-up starting at the age of 35 years, 2049 persons were diagnosed with knee OA. The adjusted HR (95% CI) of incident knee OA was 1.12 (1.06 to 1.18) for each SD of knee extensor strength and 1.18 (1.15 to 1.21) per 5 kg of body weight. Fifteen per cent of the increase in OA risk due to higher knee extensor strength could be attributed to knee injury and adult occupation. CONCLUSION: Higher knee extensor strength in adolescent men was associated with increased risk of knee OA by middle age, challenging the current tenet of low muscle strength being a risk factor for OA. We confirmed higher weight to be a strong risk factor for knee OA.

Hypertensive Disorders of Pregnancy and Offspring Cardiac Structure and Function in Adolescence.

BACKGROUND: Fetal exposure to preeclampsia is associated with higher blood pressure and later risk of stroke. We aimed to investigate the associations of maternal preeclampsia, gestational hypertension, and maternal blood pressure change in pregnancy with offspring cardiac structure and function in adolescence. METHODS AND RESULTS: Using data from a prospective birth cohort study, we included offspring who underwent echocardiography (mean age, 17.7 years; SD, 0.3; N=1592). We examined whether hypertensive disorders of pregnancy were associated with offspring cardiac structure and systolic/diastolic function using linear regression. Using multilevel linear spline models (measurement occasions within women), we also investigated whether rate of maternal systolic/diastolic blood pressure change during pregnancy (weeks 8-18, 18-30, 30-36, and 36 or more) were associated with offspring outcomes. Main models were typically adjusted for maternal age, offspring age and sex, prepregnancy body mass index, parity, glycosuria/diabetes mellitus, education, and maternal smoking. Exposure to maternal preeclampsia (0.025; 95% CI, 0.008-0.043) and gestational hypertension (0.010; 0.002-0.017) were associated with greater relative wall thickness. Furthermore, preeclampsia was also associated with a smaller left ventricular end-diastolic volume (-9.0 mL; -15 to -3.1). No associations were found between hypertensive disorders of pregnancy and offspring cardiac function. Positive rate of maternal systolic blood pressure change during weeks 8 to 18 was associated with greater offspring left ventricular end-diastolic volume, left ventricular mass indexed to height2.7, and E/A. CONCLUSIONS: Adolescent offspring exposed to maternal preeclampsia had greater relative wall thickness and reduced left ventricular end-diastolic volume, which could be early signs of concentric remodeling and affect future cardiac function as well as risk of cardiovascular disease.

Muscle strength in adolescent men and risk of cardiovascular disease events and mortality in middle age: a prospective cohort study.

BACKGROUND: Ischemic heart disease and stroke are two severe types of cardiovascular disease (CVD), a major contributor to the global burden of disease. The preventive framework currently includes promotion of both adequate cardiorespiratory and muscular fitness. Although muscle fitness is established as an indicator of health, it is currently unknown whether muscle strength is associated with later CVD independently of cardiorespiratory fitness. METHODS: We studied 38,588 Swedish men who in 1969 to 1970 (typically aged 18 years) completed compulsory conscription. Using the mean standardized score of three isometric muscle strength tests performed at conscription (hand grip, elbow flexion and knee extension), we categorized the subjects into three groups with the 25th to 75th percentile defining the reference category. We followed the cohort until 2012 for diagnosed CVD events and mortality via national health care registers and the national cause of death register. To estimate hazard ratios (HR) for CVD events (coronary heart disease or stroke) and CVD mortality we used Cox proportional hazard models adjusted for body mass index, smoking, alcohol consumption, cardiorespiratory fitness and socioeconomic status. RESULTS: Men with high muscle strength in adolescence had a decreased risk of later CVD events (HR 0.88, 95% confidence interval 0.77 to 0.99), whereas we observed no increased risk in men with low muscle strength (0.99, 0.86 to 1.13). However, low muscle strength was associated with increased risk of CVD mortality during middle age (1.31, 1.02 to 1.67). CONCLUSIONS: Muscle strength in adolescent men is inversely associated with later CVD events and CVD mortality in middle age, independently of cardiorespiratory fitness and other important confounders. Thus, the role of muscle fitness in the prevention and pathogenesis of CVD warrants increased attention.

Muscle strength in adolescent men and future musculoskeletal pain: a cohort study with 17 years of follow-up.

OBJECTIVES: Musculoskeletal pain is highly prevalent throughout adulthood with a major impact on health, function and participation in the society. Still, the association between muscle strength and development of musculoskeletal pain is unclear. We aimed to study whether overall muscle strength in adolescent men is inversely associated with self-reported musculoskeletal pain in adulthood. DESIGN: Cohort study with baseline data from the Swedish Conscription Register and outcome information from the random population-based Swedish Living Conditions Surveys. SETTING: Sweden, 1970-2005. PARTICIPANTS: 5489 men who at age 17-19 years tested their isometric muscle strength (hand grip, arm flexion and knee extension) during the compulsory conscription. OUTCOME MEASURES: The men were surveyed regarding self-reported musculoskeletal pain; mean follow-up time of 17 (range 1-35) years. Our primary outcome was a self-report of musculoskeletal pain, and secondary outcomes were a report of 'severe pain', 'pain in back/hips', 'pain in neck/shoulders' or 'pain in arms/legs', respectively. We categorised muscle strength into three groups: low, average and high, using the 25th-75th percentile to define the reference category (average). We estimated relative risks using log binomial regression with adjustment for smoking, body mass index, education and physical activity. RESULTS: In the adjusted model, men with low overall muscle strength had decreased risk of self-reported musculoskeletal pain (0.93, 95% CI 0.87 to 0.99). We observed no such association in men with high strength (0.99, 0.93 to 1.05). Furthermore, no statistically significant increase or decrease in risk was observed for any of the secondary outcomes. CONCLUSIONS: In men, low overall isometric muscle strength in youth was not associated with an increased risk of future musculoskeletal pain. Contrarily, we observed a slightly decreased risk of self-reported musculoskeletal pain in adulthood. Our results do not support a model in which low muscle strength is a risk factor for future musculoskeletal pain.

The grade in physical education in adolescence as predictor for musculoskeletal pain diagnoses three decades later.

We hypothesized that a low grade in physical education (PE) is associated with an increased risk of future musculoskeletal conditions, especially chronic pain. Using a historical cohort study design, we identified all students (mean age 16.0 years), who in 1974-1976 graduated from compulsory school in a Swedish municipality and retrieved their PE grades. We ensured that persons were still alive and resident in the county in 2003-2007 and linked data to the Skåne Health Care Register covering all in- and outpatient care in the county. Diagnoses in focus were soft tissue pain, back pain, and osteoarthritis registered as ICD-10 codes. We used a logistic regression model adjusted for education and occupation to investigate the associations between the PE grade and a future musculoskeletal diagnosis. An average grade served as reference group. Of 2298 graduates born 1957-1962, 1712 (74.5%) were resident in the county at follow-up. Women with a low (bad) PE grade had an increased odds ratio (OR) for a musculoskeletal diagnosis OR=1.5 (95% CI=1.0-2.2) as well as for the subgroup "Other soft tissue disorders, not elsewhere classified" (M79) OR=1.9 (95% CI=1.0-3.3), containing mostly chronic soft tissue pain disorders. In men with a high (good) PE grade, we found a decreased risk for "Soft tissue disorders" (M60-M79) OR=0.54 (95% CI=0.33-0.86) as well as for the subgroup "Other enthesopathies" (M77) OR=0.29 (95% CI=0.11-0.78). This study indicates that adolescent girls with a low PE grade could be an important group to target with early interventions to reduce future musculoskeletal illness.