Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Influence of cardiorespiratory fitness on obesity-associated inflammation in women and men: The FATCOR study.

BACKGROUND AND AIMS: Cardiorespiratory fitness has been postulated to lower chronic inflammation in obesity. We assessed sex-specific associations of inflammation with cardiorespiratory fitness in overweight and obese persons. METHODS AND RESULTS: Peak oxygen uptake (VO2max) was measured by treadmill in 566 participants (age 48 ± 9 years, 60% women) with body mass index >27.0 kg/m2 in the FAT associated CardiOvasculaR dysfunction (FATCOR) study. Fitness was identified from age- and sex specific reference levels of VO2max. The inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), kynurenine:tryptophan ratio (KTR) and pyriodoxic acid ratio (PAr) were measured by mass spectrometry. In the total study population 63% had obesity and 74% were cardiorespiratory unfit. Unfit women had the highest fat percentage and the highest serum levels of CRP and SAA (p < 0.05). In multivariable linear regression analyses in women, higher CRP (ß -0.15, p = 0.001), SAA (ß -0.10, p = 0.03) and PAr (ß -0.09, p = 0.03) were associated with lower VO2max after adjusting for confounders. In multivariable analyses in men, higher PAr (ß -0.14, p = 0.02) was associated with lower VO2max. In multivariable analyses in obese women, higher CRP and PAr remained associated with lower VO2max (p < 0.05), while in obese men there was no significant association. When normalizing VO2max for fat-free mass (VO2maxFFM) higher CRP, SAA and PAr index were associated with lower VO2maxFFM in women, while only higher PAr index was associated with lower VO2maxFFM in men. CONCLUSION: The association of inflammation with lower cardiorespiratory fitness was more pronounced in women than men, in particular when obesity was present. CLINICAL TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov NCT02805478.

Factors associated with progression of arterial stiffness in ischemic stroke survivors: the Norwegian Stroke in the Young Study.

BACKGROUND: Progressive arterial stiffening may increase the risk of recurrent cardiovascular events in ischemic stroke survivors. Information about factors associated with progressive arterial stiffening during the follow-up of young patients with ischemic stroke is lacking. METHODS: Arterial stiffness by carotid-femoral pulse wave velocity (cf-PWV) and ambulatory 24-hour blood pressure (24hBP) were assessed in 81 women and 190 men ≤60 years of age included in the Norwegian Stroke in the Young (NOR-SYS) study 3 months and 5.5 years after the incident ischemic stroke, representing baseline and follow-up. Covariables of change in cf-PWV were identified using linear regression analysis. RESULTS: At baseline, women had less prevalent hypertension (53% vs. 69%, p < 0.05), and lower clinic and 24hBP than men, whereas age, obesity, and prevalence of smoking and antihypertensive drug treatment did not differ. During follow-up, systolic 24hBP remained unchanged, while diastolic 24hBP fell significantly (p < 0.01). Cf-PWV was lower in women both at baseline (7.3 m/s vs. 8.1 m/s) and at follow-up (7.3 m/s vs. 8.0 m/s, both p < 0.001), but the average change during follow-up did not differ between genders. In linear regression analysis, an increase in cf-PWV at the 5-year follow-up was associated with the presence of hypertension and lower cf-PWV at baseline, and higher systolic 24hBP and lack of use of antihypertensive treatment at follow-up (all p < 0.05). CONCLUSION: In ischemic stroke survivors participating in the NOR-SYS study, the 5-year increase in cf-PWV did not differ between genders and was associated with higher systolic 24hBP and lack of antihypertensive treatment.

Progressive arterial stiffening increases the risk of recurrent stroke. More information about factors associated with progression of arterial stiffness in young ischemic stroke survivors is needed. This study followed 81 women and 190 men for 5 years and examined changes in arterial stiffness in relation to blood pressure levels and other factors.Arterial stiffness was measured using the carotid-femoral pulse wave velocity. We also measured blood pressure at study visits and over a 24-hour period while the study participants led their daily life. Measurements were performed 3 months after the index ischemic stroke (baseline) and repeated after an average of 5.5 years of follow-up.Our main finding was that hypertension is very common and is important for arterial health in young ischemic stroke survivors. An increase in arterial stiffness during follow-up was associated with hypertension, higher 24-hour blood pressure, and lack of use of blood pressure-lowering drugs in participants with hypertension. There were no differences between women and men.This study shows the importance of proper blood pressure management in young ischemic stroke survivors to avoid progressive stiffening of the arteries. The results also demonstrated the value of using 24-hour measurements rather than office measurements in the evaluation of blood pressure control during treatment.

Factors associated with change in arterial stiffness in patients with rheumatoid arthritis: the JointHeart study.

BACKGROUND: Rheumatoid arthritis (RA) predominantly affects women and is associated with hypertension and arterial stiffness. We explored factors associated with change in arterial stiffness in patients with RA treated with disease-modifying antirheumatic drug (DMARD) therapy. METHODS: Seventy-seven outpatients with RA (age 55 ± 11, 69% women), with indication for treatment with biological or targeted synthetic DMARDs, were included. Pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx) and Disease Activity Score in 28 joints (DAS28) were measured at baseline and after a mean of 22 months of follow-up. RESULTS: At follow-up, 83% used DMARDs and 73% had achieved remission or low disease activity. DAS28 decreased from 3.8 ± 1.3 to 2.8 ± 1.2 (p < 0.001). Mean PWV increased from 7.8 ± 1.6 m/s at baseline to 8.5 ± 1.8 m/s at follow-up (p < 0.001), while AP and AIx were stable. Increase in PWV during follow-up was associated with increase in systolic blood pressure (BP), diabetes, higher DAS28 and body mass index (BMI) at baseline, independent of achieved remission/low disease activity and use of DMARDs at follow-up. In multivariable analyses at follow-up, female sex was associated with higher AP and AIx, but with lower PWV, after adjusting for possible confounders. CONCLUSION: In patients with RA, higher disease activity, BMI and diabetes at baseline, together with increase in office systolic BP were associated with an increase in arterial stiffness during follow-up, despite DMARD therapy. This highlights the need for management of cardiovascular risk factors in addition to reducing the inflammatory load in patients with RA to preserve arterial function.

Rheumatoid arthritis (RA) affects women more often than men and leads to chronic inflammation and faster stiffening of the arteries. In this study, we identified factors that were associated with increase in arterial stiffness during 22 months of follow-up in patients with RA treated with modern antirheumatic medication.This study included 77 patients with RA (69% women), that were in need of change in their disease-modifying antirheumatic medication.We measured arterial stiffness at baseline and repeated it after 22 months of follow-up.At follow-up, arterial stiffness had increased while the disease activity had improved. The rise in arterial stiffness was associated with having diabetes, higher body mass index and higher disease activity at the start of the study and with experiencing an increase in blood pressure during follow-up.This study highlights the need for maintaining a healthy lifestyle and treating cardiovascular risk factors like blood pressure and obesity in patients with RA beyond using modern antirheumatic medication to avoid stiffening of the arteries.

High-normal blood pressure in midlife is a stronger risk factor for incident hypertension 26 years later in women than men: the Hordaland Health Study.

PURPOSE: To identify modifiable risk factors in early midlife associated with incident hypertension 26 years later in women and men. MATERIALS AND METHODS: We used data from 1025 women and 703 men in the community-based Hordaland Health Study examined at the mean age of 42 years (baseline) and after a 26-year follow-up. Patients with hypertension at baseline were excluded. Blood pressure (BP) was classified according to European guidelines. Factors associated with incident hypertension were identified in logistic regression analyses. RESULTS: At baseline, women had a lower average BP and a lower prevalence of high-normal BP (19% vs 37%, p < .05). Overall, 39% of women and 45% of men developed hypertension during follow-up (p < .05). Among those with high-normal BP at baseline, 72% of women and 58% of men developed hypertension (p < .01). In multivariable logistic regression analyses, high-normal BP at baseline was a stronger predictor of incident hypertension in women (odds ratio, OR 4.8, [95% confidence interval, CI 3.4-6.9]) than in men (OR 2.1, [95% CI 1.5-2.8]), p < .01 for sex interaction. A higher baseline body mass index (BMI) was associated with incident hypertension in both sexes. CONCLUSIONS: High-normal BP in midlife is a stronger risk factor for developing hypertension 26 years later in women than in men, independent of BMI.

There is a knowledge gap regarding the understanding of sex differences in hypertension and cardiovascular disease. The World Health Organisation has identified hypertension as the leading cause of morbidity and mortality in women.This manuscript focuses on sex differences in risk factors in early midlife associated with the development of hypertension 26 years later. We studied 1025 women and 703 men who participated in the community-based Hordaland Health Study at the age of 42 years, and after 26 years. Factors associated with hypertension were identified in statistical analyses.Our main findings were that having a high-normal blood pressure (systolic blood pressure 130­139 mmHg or a diastolic blood pressure 85­89 mmHg) in midlife was a significantly stronger risk factor for the development of hypertension in women than in men during follow-up. Having a higher body mass index in midlife was associated with the development of hypertension in both sexes.This study contributes to the understanding of sex differences in hypertension development and adds further knowledge regarding high-normal blood pressure as a particularly important risk factor for hypertension and cardiovascular disease in women.

Cardiovascular organ damage in relation to hypertension status in patients with ankylosing spondylitis.

PURPOSE: Hypertension is a major cardiovascular (CV) risk factor in ankylosing spondylitis (AS) patients. Less is known about the prevalence of CV organ damage in relation to hypertension status in AS patients. MATERIALS AND METHODS: CV organ damage was assessed by echocardiography, carotid ultrasound and pulse wave velocity (PWV) by applanation tonometry in 126 AS patients (mean age 49 ± 12 years, 39% women) and 71 normotensive controls (mean age 47 ± 11 years, 52% women). CV organ damage was defined as presence of abnormal left ventricular (LV) geometry, LV diastolic dysfunction, left atrial (LA) dilatation, carotid plaque or high pulse wave velocity (PWV). RESULTS: Thirty-four percent of AS patients had hypertension. AS patients with hypertension were older and had higher C-reactive protein (CRP) levels compared to AS patients without hypertension and controls (p < 0.05). The prevalence of CV organ damage was 84% in AS patients with hypertension, 29% in AS patients without hypertension and 30% in controls (p < 0.001). In multivariable logistic regression analyses, having hypertension was associated with a fourfold increased risk of CV organ damage independent of age, presence of AS, gender, body mass index, CRP, and cholesterol (odds ratio (OR) 4.57, 95% confidence interval (CI) 1.53 to 13.61, p = 0.006). In AS patients, presence of hypertension was the only covariable significantly associated with presence of CV organ damage (OR 4.40, 95% CI 1.40 to 13.84, p = 0.011). CONCLUSIONS: CV organ damage in AS was strongly associated with hypertension, pointing to the importance of guideline-based hypertension management in AS patients.

What is the context? Ankylosing spondylitis (AS) is an inflammatory disease primarily affecting the spine. Patients with AS have increased risk for cardiovascular disease. High blood pressure (hypertension) is both very common in AS patients, and a major risk factor for developing cardiovascular disease. Hypertension leads to structural and functional changes in the heart and arteries, referred to as cardiovascular organ damage. However, little is known about the prevalence of cardiovascular organ damage in AS patients with hypertension.What is new? Using ultrasound and tonometry, we assessed organ damage in the heart and arteries in AS patients with hypertension and compared them to AS patients with normal blood pressure as well as a group of healthy controls. We found that 84% of the AS patients with hypertension had cardiovascular organ damage, compared to 29% of AS patients with normal blood pressure and 30% of controls. Independent of other risk factors, hypertension was associated with a fourfold increased risk of cardiovascular organ damage in AS patients.What is the impact? These findings are important because cardiovascular organ damage is potentially reversible with treatment. Our results underline the significance of guideline-directed hypertension management in AS patients to reduce cardiovascular disease.

Impact of aortic valve stenosis on myocardial deformation in different left ventricular levels: A three-dimensional speckle tracking echocardiography study.

BACKGROUND: Global systolic left ventricular (LV) myocardial function progressively declines as degenerative aortic valve stenosis (AS) progresses. Whether this results in uniformly distributed deformation changes from base to apex has not been investigated. METHODS: Eighty-five AS patients underwent three-dimensional (3D) echocardiography in this cross-sectional study. Patients were grouped by peak jet velocity into mild (n = 32), moderate (n = 31), and severe (n = 22) AS. 3D speckle tracking derived strain, rotation, twist, and torsion were obtained to assess global LV function and myocardial function at the apical, mid, and basal levels. RESULTS: Global longitudinal strain (GLS) was lower in patients with severe AS (-16.1 ± 2.4% in mild, -15.5 ± 2.5% in moderate, and -13.5 ± 3.0% in severe AS [all p < .01]). Peak basal and mid longitudinal strain (LS), basal rotation and twist from apical to basal level followed the same pattern, while peak apical LS was higher in moderate AS compared to severe AS (all p < .05). In multivariate analyses, lower GLS was particularly associated with male sex, higher body mass index and peak aortic jet velocity, lower basal LS with higher filling pressure (E/e') and LV mass, lower mid LS with higher RWT and presence of AS symptoms, and lower apical LS with male sex and higher systolic blood pressure, respectively (all p < .05). CONCLUSION: Using 3D speckle tracking echocardiography reveals regional and global changes in LV mechanics in AS related to the severity of AS, LV remodeling and presence of cardiovascular risk factors.

Sex differences in arterial hypertension.

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension.

Aortic Root Dilatation in Hypertensive Patients with Left Ventricular Hypertrophy-Application of A New Multivariate Predictive Model. The Life Study.

BACKGROUND: Available nomograms to predict aortic root (AoR) diameter for body surface area have limitations. The purpose of this study was to evaluate the use of a new multivariate predictive model to identify AoR dilatation in hypertensive patients with left ventricular hypertrophy. METHODS: 943 of 961 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic sub-study had the necessary baseline characteristics and echocardiographic 2D measurements of AoR size to be included. RESULTS: Predicted AoR (Sinus of Valsalva) diameter was 1.519 + (age [years] × 0.010) + (height [cm] × 0.010) - (gender [1 = M, 2 = F] × 0.247), and a measured AoR diameter exceeding the 97.5-percentile of this estimate was considered dilated. Measured AoR diameter was larger in men than in women (3.75 vs. 3.48 cm, p < 0.001) and AoR diameter predicted by the model was larger than predicted by nomogram (3.52 vs. 3.28 cm, p < 0.001). Using the multivariate model to identify patients with AoR dilatation, the prevalence was 13.7% in men and 12.3% in women (p = 0.537). There was consensus of AoR phenotype (normal/dilated) between model and nomogram in 92.8% of the patients. In multivariate logistic regression, AoR dilatation by model definition was predicted by presence of aortic regurgitation (OR 2.67, p < 0.001) and SD increase in age (OR 0.75, p = 0.023), pulse pressure (OR 0.64, p < 0.001), left ventricular mass index (OR 1.36, p = 0.08) and stroke volume (OR 1.45, p = 0.002), but not by body weight. CONCLUSIONS: Using the proposed model the prevalence of AoR dilatation was equal in men and women and the model seems to address the effects of gender, age and body size on AoR size. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00338260.

Orientation of the Atrial Septum to the Inferior Vena Cava May Contribute to the Persistent Patency of the Foramen Ovale.

PURPOSE: There is growing evidence that paradoxical embolism through patent foramen ovale (PFO) is a cause for cryptogenic stroke. However, it is still unclear why the foramen ovale fails to close after birth. We studied whether the 3D relations between the atrial septum (AS) and the inferior vena cava (IVC) are associated with PFO. METHODS: We recruited 30 patients (18-49 years) with a first-ever cryptogenic stroke and 30 age- and sex-matched stroke-free controls. Using cardiac magnetic resonance, an approach to evaluate the 3D relations between the AS and the IVC was developed. The presence of interatrial right-to-left shunt was evaluated with transesophageal echocardiography (TEE) in patients and transcranial Doppler in controls. RESULTS: Of 30 patients, 29 underwent successful TEE, of which 12 (41%) had a shunt. Patients with a shunt had a greater mean 3D angle (γ) between the atrial septal plane and the vector from the orifice of the IVC to the middle of the AS compared with patients without a shunt (45 ± 9° vs. 36 ± 8°, p = 0.017). Of 30 controls, 12 (40%) had a shunt and a greater mean γ compared with controls without a shunt (47 ± 8° vs. 37 ± 10°, p = 0.007). In a pooled analysis, 24 (41%) of 59 subjects with a shunt had a mean γ of 46 ± 9° compared with subjects without a shunt of 37 ± 9° (p < 0.001). CONCLUSIONS: More perpendicular orientation of the atrial septal plane to the orifice of the IVC is associated with PFO, possibly by directing the IVC flow to PFO.

Left ventricular myocardial oxygen demand and subclinical dysfunction in patients with severe obesity referred for bariatric surgery.

BACKGROUND AND AIMS: Increased myocardial oxygen (O2) demand carries higher cardiovascular risk in hypertension. We hypothesized that myocardial O2 demand is increased in severe obesity and linked to early left ventricular (LV) dysfunction. METHODS AND RESULTS: Baseline data from 106 severely obese subjects referred for gastric bypass surgery (42 ± 11 years, 74% women, body mass index [BMI] 41.9 ± 4.8 kg/m2, 32% with hypertension) in the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study was used. LV systolic function was assessed by biplane ejection fraction (EF), midwall shortening (MWS) and endocardial global longitudinal strain (GLS), and LV diastolic function by mitral annular early diastolic velocity (e'). Myocardial O2 demand was estimated from the LV mass-wall stress-heart rate product (high if > 1.62 × 106/2.29 × 106 g kdyne/cm2 bpm in women/men). High myocardial O2 demand was found in 33% and associated with higher BMI and high prevalence of low GLS (65%) and low MWS (63%) despite normal EF. In ROC analyses, higher myocardial O2 demand discriminated between patients with low vs. normal MWS and GLS (area under curve 0.71 and 0.63, p < 0.05). In successive multiple regression analyses, higher myocardial O2 demand was associated with lower LV MWS, GLS and average e', respectively, independent of age, gender, BMI, pulse pressure, diabetes mellitus, and EF (all p < 0.05). CONCLUSION: In obese patients without known heart disease and with normal EF referred for bariatric surgery, high myocardial O2 demand is associated with lower myocardial function whether assessed by GLS or MWS independent of confounders. CLINICALTRIALS. GOV IDENTIFIER: NCT01533142.

Preclinical cardiac disease in women and men with primary aldosteronism.

PURPOSE: We tested the sex-specific associations between primary aldosteronism (PA), left ventricular (LV) hypertrophy and LV systolic myocardial function. MATERIAL AND METHODS: Conventional and speckle tracking echocardiography was performed in 109 patients with PA and 89 controls with essential hypertension (EH). LV hypertrophy was identified if LV mass index exceeded 47.0 g/m2.7 in women and 50.0 g/m2.7 in men. LV systolic myocardial function was assessed by global longitudinal strain (GLS) and midwall shortening. RESULTS: PA patients had higher prevalence of LV hypertrophy (52 vs. 21%, p < 0.001) than EH patients in both sexes, while GLS did not differ by sex or hypertension aetiology. In multivariable analyses, presence of LV hypertrophy was associated with PA and obesity in both sexes, while lower systolic myocardial function, whether measured by GLS or midwall shortening, was not associated with PA, but primarily with higher body mass index and LV mass index, respectively, in both sexes (all p < 0.05). CONCLUSION: Having PA was associated with higher prevalence of LV hypertrophy both in women and men, compared to EH. PA was not associated with LV systolic myocardial function in either sex.

Prognostic impact of impaired left ventricular midwall function during progression of aortic stenosis.

OBJECTIVE: In hypertension, indexes of midwall left ventricular (LV) function may identify patients at higher cardiovascular (CV) risk independent of normal LV ejection fraction (EF). We analyzed the association of baseline and new-onset LV midwall dysfunction with CV outcome in a large population of patients with asymptomatic aortic stenosis (AS). METHODS: One thousand four hundred seventy-eight patients with asymptomatic AS and normal EF (≥50%) at baseline in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a median of 4.3 years. LV systolic function was assessed by biplane EF and midwall shortening (MWS, low if <14% in men/16% in women) at baseline and annual echocardiographic examinations. RESULTS: One hundred twenty-three CV deaths and heart failure hospitalizations occurred during follow-up. In Cox analyses, adjusting for age, gender, body mass index, hypertension, EF, AS severity, LV hypertrophy and systemic arterial compliance, low baseline MWS predicted 61% higher risk of a major CV event and a twofold higher risk of death and heart failure hospitalization (P < .05). New-onset low MWS developed in 574 patients, particularly in elderly women with higher blood pressure and more severe AS (P < .05). In time-varying Cox analysis, new-onset low MWS was associated with a twofold higher risk of CV death and heart failure hospitalization, independent of changes over time in EF, AS severity, LV hypertrophy and systemic arterial compliance (P < .05). CONCLUSIONS: Low MWS develops in a large proportion of patients with AS and normal EF during valve disease progression and is a marker of increased CV risk.

Long-term blood pressure trajectories and incident atrial fibrillation in women and men: the Tromsø Study.

AIMS: To explore sex-specific associations between long-term individual blood pressure (BP) patterns and risk of incident atrial fibrillation (AF) in the general population. METHODS AND RESULTS: Blood pressure was measured in 8376 women and 7670 men who attended at least two of the three population-based Tromsø Study surveys conducted in 1986-87, 1994-95, and 2001. Participants were followed for incident AF throughout 2013. Latent mixed modelling was used to identify long-term trajectories of systolic BP and hypertension. Cox regression was used to estimate associations between the identified trajectories and incident AF. Elevated systolic BP throughout the exposure period (1986-2001) independently and differentially increased risk of AF in women and men. In women, having elevated systolic BP trajectories doubled AF risk compared to having persistently low levels, irrespective of whether systolic BP increased, decreased, or was persistently high over time, with hazard ratios of 1.88 (95% confidence interval 1.37-2.58), 2.32 (1.61-3.35), and 1.94 (1.28-2.94), respectively. In men, those with elevated systolic BP that continued to increase over time had a 50% increased AF risk: 1.51 (1.09-2.10). When compared to those persistently normotensive, women developing hypertension during the exposure period, and women and men with hypertension throughout the exposure period had 1.40 (1.06-1.86), 2.75 (1.99-3.80), and 1.36 (1.10-1.68) times increased risk of AF, respectively. CONCLUSION: Long-term BP and hypertension trajectories were associated with increased incidence of AF in both women and men, but the associations were stronger in women.

Preclinical cardiac organ damage during statin treatment in patients with inflammatory joint diseases: the RORA-AS statin intervention study.

OBJECTIVE: Statin treatment has been associated with reduction in blood pressure and arterial stiffness in patients with inflammatory joint diseases (IJD). We tested whether statin treatment also was associated with regression of preclinical cardiac organ damage in IJD patients. METHODS: Echocardiography was performed in 84 IJD patients (52 RA, 20 ankylosing spondylitis, 12 psoriatric arthritis, mean age 61 (9) years, 63% women) without known cardiovascular disease before and after 18 months of rosuvastatin treatment. Preclinical cardiac organ damage was identified by echocardiography as presence of left ventricular (LV) hypertrophy, LV concentric geometry, increased LV chamber size and/or dilated left atrium. RESULTS: At baseline, hypertension was present in 63%, and 36% used biologic DMARDs (bDMARDs). Preclinical cardiac organ damage was not influenced by rosuvastatin treatment (44% at baseline vs 50% at follow-up, P = 0.42). In uni- and multivariable logistic regression analyses, risk of preclinical cardiac organ damage at follow-up was increased by higher baseline body mass index [odds ratio (OR) 1.3, 95% CI: 1.1, 1.5, P = 0.01] and presence of preclinical cardiac organ damage at baseline (OR 6.4, 95% CI: 2.2, 18.5, P = 0.001) and reduced by use of bDMARDs at follow-up (OR 0.3, 95% CI: 0.1, 0.9, P = 0.03). CONCLUSION: Rosuvastatin treatment was not associated with a reduction in preclinical cardiac organ damage in IJD patients after 18 months of treatment. However, use of bDMARDS at follow-up was associated with lower risk of preclinical cardiac organ damage at study end, pointing to a possible protective cardiac effect of bDMARDs in IJD patients. CLINICALTRIALS.GOV: https://clinicaltrials.gov/NCT01389388.

Factors associated with increase in blood pressure and incident hypertension in early midlife: the Hordaland Health Study.

Purpose: We aimed to identify sex-specific factors associated with increase in blood pressure (BP) and incident hypertension in early midlife.Materials and methods: 2,008 women and 1,610 men aged 40-43 years were followed for six years in the Hordaland Health Study. Participants taking antihypertensive medication at baseline were excluded. High-normal BP was defined as baseline BP 130-139/85-89 mmHg, and incident hypertension as BP≥140/90 mmHg or use of antihypertensive medication at follow-up.Results: During follow-up, an increase in systolic (SBP) and diastolic (DBP) BP was observed in 54% and 30% of women vs. 44% and 41% of men, respectively (both p<0.001). In both sexes higher baseline body mass index (BMI) and increases in BMI and serum lipids were associated with increases in SBP and DBP during follow-up (all p<0.05). Incident hypertension was more common in men (14 vs.11%, p<0.01), and predicted by higher BMI and high-normal BP at baseline in both sexes, and by higher serum triglyceride level in women (all p<0.01). Conclusion: In the Hordaland Health Study, BP development differed between women and men in early midlife. The main factors associated with BP increase in both sexes were higher BMI, weight gain and increases in serum lipids.

Prognostic impact of increased pulse pressure/stroke index in a registry of hypertensive patients: the Campania Salute Network.

Objectives: Increased arterial stiffness is associated with advanced arteriosclerosis, abnormal left ventricular (LV) geometry and function. Whether increased arterial stiffness is associated with incident cardiovascular (CV) event (MACE), independent of other markers of target organ damage needs to be clarified. Methods: We selected hypertensive participants of the Campania Salute Network free of prevalent CV disease, with available echocardiogram and carotid ultrasound, ejection fraction ≥50%, and ≤ stage III Chronic Kidney Disease (n = 6907). Median follow-up was 63 months. End-point was incident MACE (fatal and non-fatal stroke and myocardial infarction, sudden cardiac death, carotid stenting and heart failure requiring hospitalization). Arterial stiffness was assessed from ratio of brachial pulse pressure/stroke index (i.e. normalized for body height in meter to 2.04 power) (PP/SVi). High PP/SVi (n = 980) was defined as >95th sex-specific percentile of the normal distribution from a reference normal population (>2.63/>2.82 mmHg/ml in men and women, respectively). Results: Patients with high PP/SVi were more likely to be women, older, diabetic, with higher systolic blood pressure (BP) and heart rate, more LV concentric geometry, left atrial dilatation and more carotid plaque (all p < .01). At given increase in SVi, patients with high PP/SVi exhibited two-fold increase in PP compared to normal PP/SVi. In Cox regression, patients with high PP/SVi had 63% increased hazard of MACE [95% CI (1.02-2.59) p = .04], independently of significant effect of older age, male sex, carotid plaque and less frequent anti-RAS therapy. Conclusions: In treated hypertensive patients, high PP/SVi predicted increased rate of MACE, independent of common confounders.

Prevalence and covariates of uncontrolled hypertension in ischemic stroke survivors: the Norwegian stroke in the young study.

PURPOSE: Hypertension is the most important modifiable risk factor for stroke. Few data are available on control of hypertension in younger ischemic stroke survivors. MATERIAL AND METHODS: We assessed clinic and ambulatory blood pressure (BP) measurements in 320 patients aged 15-60 years (mean 48 ± 10) included in the Norwegian Stroke in the Young Study during 3-months follow-up after the index stroke. Controlled hypertension was defined as ambulatory BP <130/80 mmHg. Carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry. Carotid plaque was considered present if focal intima-media thickness >1.5 mm. RESULTS: At hospital discharge, 58% of the patients were treated for hypertension. Another 9% of the total study population was diagnosed with new-onset hypertension during follow-up. At the 3-months follow-up visit, 56% of patients with treated hypertension were uncontrolled. Patients with uncontrolled treated hypertension were older, had higher body mass index (BMI) and PWV, and were more likely to have diabetes and carotid plaques compared to patients with normotension (p < .01). Compared to controlled treated hypertension, patients with uncontrolled treated hypertension had higher prevalence of carotid plaque (p < .01). In a multivariate logistic regression, uncontrolled treated hypertension was associated with higher PWV and BMI, and presence of carotid plaque, independent of the more intensified use of antihypertensive treatment (all p < .05). CONCLUSION: Uncontrolled hypertension was highly prevalent in ischemic stroke survivors <60 years and associated with co-presence of obesity and functional and structural arterial damage. Our results highlight the unmet potential and challenge of optimization of hypertension diagnosis and management in order to prevent recurrent vascular events in ischemic stroke survivors.

Disease activity is associated with reduced left ventricular systolic myocardial function in patients with rheumatoid arthritis.

OBJECTIVES: Disease activity has emerged as a new, independent risk factor for cardiovascular disease in patients with rheumatoid arthritis (RA). We tested if disease activity in RA was associated with lower left ventricular (LV) systolic function independent of traditional cardiovascular risk factors. METHODS: Echocardiographic assessment was performed in 78 patients with RA having low, moderate or high disease activity (Simplified Disease Activity Index (SDAI) >3.3), 41 patients in remission (SDAI ≤3.3) and 46 controls, all without known cardiac disease. LV systolic function was assessed by biplane Simpson ejection fraction, stress-corrected midwall shortening (scMWS) and global longitudinal strain (GLS). RESULTS: Patients with active RA had higher prevalence of hypertension and diabetes compared with patients in remission and controls (both p<0.05). LV ejection fraction (endocardial function) was normal in all three groups, while mean scMWS and GLS (myocardial function) were reduced in patients with RA with active disease compared with patients with RA in remission (95±18% vs 105±17% and -18.9±3.1% vs -20.6±3.5%, respectively, both p<0.01). Patients with RA in remission had similar scMWS and GLS as the controls. In multivariable analyses, having active RA was associated with lower GLS (ß=0.21) and scMWS (ß=-0.22, both p<0.05), both reflecting lower LV systolic myocardial function, independent of cardiovascular risk factors and LV ejection fraction. Classification of RA disease activity by other disease activity composite scores yielded similar results. CONCLUSIONS: Active RA is associated with lower LV systolic myocardial function despite normal ejection fraction and independent of traditional cardiovascular risk factors.

Higher pulse pressure/stroke volume index is associated with impaired outcome in hypertensive patients with left ventricular hypertrophy the LIFE study.

We tested the prognostic impact of a marker of arterial stiffness, pulse pressure/stroke volume index (PP/SVi), in patients with hypertension and left ventricular (LV) hypertrophy. We used data from 866 patients randomized to losartan or atenolol-based antihypertensive treatment, over a median of 4.8 years, in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. The association of PP/SVi with outcomes was tested in Cox regression analyses and reported as hazard ratio (HR) and 95% confidence intervals (CI). In multivariate regression, reduction of PP/SVi was independently associated with male gender, reduction in systolic blood pressure (BP) and relative wall thickness and with an increase in left ventricular ejection fraction (all p < .05). After adjusting for confounders, higher baseline PP/SVi predicted a 38% higher hazard of combined major fatal and non-fatal cardiovascular events (95% CI 1.04-1.84), and higher hazard of cardiovascular mortality (HR 2.35 (95% CI 1.59-3.48) and stroke (HR 1.45 (95% CI 1.06-1.99) (all p < .05). Higher PP/SVi also predicts higher rate of hospitalization for HF (HR 2.15 (95% CI 1.48-3.12) and a 52% higher hazard of all-cause mortality (95% CI 1.10-2.09) (both p < .05). In hypertensive patients with electrocardiographic LV hypertrophy, higher PP/SVi was associated with increased cardiovascular morbidity and mortality.