Sex differences in blood pressure in midlife: associations with risk factors and acute coronary syndromes in the Hordaland Health Studies

Bakgrunn: Blant unge voksne har friske kvinner vanligvis lavere blodtrykk (BT) enn menn. Men allerede fra 20-årene har kvinner en brattere stigning i BT enn menn på samme alder. Målet med dette arbeidet var å identifisere faktorer assosiert med BT og BT-endring i 40 årene og sammenhengen mellom BT tidlig i 40 årene og risiko for sykehusinnleggelse eller død av akutt koronarsyndrom (AKS) i løpet av 16 års oppfølging hos kvinner og menn. Materiale og metode: Arbeidet er basert på data fra den befolkningsbaserte Helseundersøkelsen i Hordaland (HUSK) og «Cardiovascular Disease in Norway Project 1994-2009» (CVDNOR). CVDNOR inneholder informasjon om alle sykehusinnleggelser og dødsfall i Norge med en hjertekar- eller diabetesdiagnose i perioden 1994-2009. Studiedeltagerne i HUSK fikk utført standardiserte BT-målinger og det ble samlet inn informasjon om kardiovaskulære risikofaktorer da de var gjennomsnittlig 41 år gamle i HUSK1 (baseline) og 6 år senere i HUSK2. Informasjon om sykehusinnleggelser eller død av AKS i løpet av 16 års oppfølgingstid ble hentet fra CVDNOR. Inflammasjonsmarkører, inkludert høysensitivt C-reaktivt protein (hs-CRP), neopterin og pyridoksal syre ratio (PAr), ble målt i HUSK2. Resultat: I studie 1 var høyere BT og kroppsmasse indeks (KMI) målt ved baseline, og stigning i KMI, kolesterol og triglyserider fra HUSK1 til HUSK 2 de viktigste faktorene assosiert med stigning i BT eller nyoppstått hypertensjon ved HUSK2 hos både kvinner og menn. I Studie 2 økte risiko for AKS med høyere BT hos begge kjønn. Kvinner som hadde et lett forhøyet BT (systolisk BT 130-139 mmHg og /eller diastolisk BT 80-89 mmHg) tidlig i 40 årene hadde doblet risiko for AKS i løpet av 16 års oppfølgingstid sammenlignet med kvinner som hadde normalt BT også etter justering for andre kardiovaskulære risikofaktorer. Tilsvarende assosiasjon fant vi ikke hos menn. Forskjellen ble dokumentert med signifikant interaksjonstest mellom BT og kjønn. I Studie 3 var hs-CRP signifikant assosiert med høyere systolisk og diastolisk BT i HUSK2, samt med nyoppstått hypertensjon de siste 6 år hos kvinner, men ikke hos menn. I tillegg var høyere serum neopterin assosiert med høyere diastolisk BT kun hos kvinner, mens høyere PAr indeks var assosiert med høyere systolisk og diastolisk BT hos menn. Disse kjønnsforskjellene ble bekreftet med signifikante interaksjonstester mellom BT og kjønn i modellen for AKS, mellom hs-CRP og kjønn i modellene for systolisk og diastolisk BT og nyoppstått hypertensjon, og mellom neopterin og kjønn i modellen for diastolisk BT. Konklusjon: Høyere baseline KMI, vektoppgang og stigning i serum lipider var de viktigste faktorene assosiert med stigning i BT og nyoppstått hypertensjon hos både kvinner og menn i 40 årene. Sammenhengen mellom inflammasjon og BT var sterkere hos kvinner enn hos menn. Å ha et lett forhøyet BT tidlig i 40 årene var en sterkere risikofaktor for AKS før fylte 60 år hos kvinner enn hos menn. Resultatene peker på et behov for kjønnsspesifikke anbefalinger for diagnostisering og forebygging av hypertensjon.Background: Among healthy young adults, women have lower blood pressure (BP) compared to their male counterparts. Then, from the third decade onwards, women have a steeper increase in BP than men. The aim of the current project was to explore factors associated with BP and BP change among women and men in their forties and to test sex-specific associations between BP in the early forties and risk of ACS over 16 years follow-up. Materials and methods: This work was performed using data from the community-based Hordaland Health Study (HUSK) and the “Cardiovascular Disease in Norway Project 1994-2009” (CVDNOR). The latter includes information about all hospital stays and deaths in Norway with a cardiovascular disease (CVD) or diabetes diagnosis in the period 1994-2009. BP was measured and information about CVD risk factors collected when participants were 41±1 years old in HUSK1 and 6 years later in HUSK2. Information about hospitalizations or death from an ACS over 16 years follow-up was obtained from the CVDNOR project. Plasma markers of inflammation, including high-sensitive C-reactive protein (hs-CRP), neopterin, and the pyridoxic acid ratio (PAr), were measured in HUSK2. Results: In study 1, initial BP, higher body mass index (BMI), weight-gain and increases in serum cholesterol and serum triglycerides were the main factors associated with increase in BP and incident hypertension from HUSK1 to HUSK2 both in women and men. In study 2, having a mildly elevated BP (systolic BP 130-139 mmHg and/or diastolic BP 80-89 mmHg) in the early forties doubled the risk of ACS over 16 years follow-up in women, compared to women with a normal BP, after adjustment for other CVD risk factors. The same association was not found in men. In study 3, after adjustment for BMI, higher levels of hs-CRP in the forties were associated with higher BP and new onset hypertension during the last 6 years in women, but not in men. Furthermore, higher levels of plasma neopterin was associated with higher diastolic BP only in women, while higher PAr was associated with higher systolic and diastolic BP in men. These sex differences were confirmed by significant interactions between BP and sex in the model on ACS, between hs-CRP and sex in the models on systolic and diastolic BP and incident hypertension, and between neopterin and sex in the model on diastolic BP. Conclusion: Among women and men in their early forties, initial BP, BMI, weight gain and increases in serum lipids were the main factors associated with increases in BP and new onset hypertension. Plasma markers of inflammation were particularly associated with higher BP level in women. Finally, having a mildly elevated BP in the early forties was a stronger risk factor for ACS before the age of 60 years in women than in men. Taken together our results suggest a need for sex-specific recommendations and actions for diagnosis and prevention of hypertension.Doktorgradsavhandlin

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.publishedVersio

Subclinical cardiac organ damage in patients with moderate to severe psoriasis

We explored the association between subclinical cardiac organ damage (OD) with comorbidities and psoriasis severity in 53 psoriasis patients on infliximab treatment (age 47 ± 15 years, 30% women) and 99 controls without psoriasis (age 47 ± 11 years, 28% women). Cardiac OD was assessed by echocardiography as the presence of increased left ventricular (LV) relative wall thickness (RWT), LV hypertrophy or dilated left atrium. Psoriasis severity was graded using the psoriasis area and severity index (PASI). The prevalence of hypertension was 66% in psoriasis vs. 61% in controls (p = 0.54) and cardiac OD seen in 51 and 73%, respectively (p = 0.007). Psoriasis was associated with a lower prevalence of cardiac OD (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.13–0.77, p = 0.01) independent of age, sex, smoking, body mass index, and hypertension. Among psoriasis patients, hypertension was associated with increased risk of subclinical cardiac OD (OR 6.88, 95% CI 1.32–35.98, p = 0.02) independent of age, sex, and body mass index. PASI at treatment initiation was associated with a higher RWT at follow-up, independent of sex, age, and hypertension (β 0.36, p = 0.006) while no association with current PASI was found. In conclusion, cardiac OD was less prevalent in psoriasis patients on infliximab treatment than controls. Hypertension was the major covariable for subclinical cardiac OD in psoriasis.publishedVersio

Arterial Stiffness in Overweight and Obesity: Association with Sex, Age, and Blood Pressure

Introduction: Obesity has been associated with increased arterial stiffness. Sex-differences in arterial stiffness in obesity have been less explored. Aim: To explore sex-differences in arterial stiffness by applanation tonometry in 323 women and 225 with overweight and obesity, free of cardiovascular disease. Methods: Covariables of arterial stiffness were identified in multivariable linear regression analyses in the total cohort and separately in women and men. Results: In the total study cohort, women had higher augmentation pressure (AP) and augmentation index (AIx), and lower carotid-femoral pulse wave velocity (cf-PWV) than men, independent of confounders (all p < 0.001). In sex-specific analyses, higher AP was associated with higher age and 24-hours systolic blood pressure (BP), and with lower heart rate in women (all p < 0.001), and with higher age and BP in men (all p < 0.001). Similarly, higher AIx was associated with higher age and BP, and lower body mass index (BMI) and heart rate in women (all p < 0.05), and with higher age in men (all p < 0.001). Higher cf-PWV correlated with higher age and BP in women (all p < 0.005), and additionally with higher heart rate and non-smoking in men (all p < 0.05). When replacing BMI with waist-hip ratio, higher waist-hip ratio was associated with higher cf-PWV in men only (p < 0.05). Conclusions: Among subjects with overweight and obesity, AP and AIx were higher in women, and cf-PWV was higher in men. Age and 24-hours systolic BP were the main factors associated with arterial stiffness in both sexes, while measures of adiposity had little impact on arterial stiffness.publishedVersio

Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study

Aims Hypertension has been suggested as a stronger risk factor for acute coronary syndromes (ACS) in women than men. Whether this also applies to stage 1 hypertension [blood pressure (BP) 130–139/80–89 mmHg] is not known. Methods and results We tested associations of stage 1 hypertension with ACS in 12 329 participants in the Hordaland Health Study (mean baseline age 41 years, 52% women). Participants were grouped by baseline BP category: Normotension (BP < 130/80 mmHg), stage 1 and stage 2 hypertension (BP ≥140/90 mmHg). ACS was defined as hospitalization or death due to myocardial infarction or unstable angina pectoris during 16 years of follow-up. At baseline, a lower proportion of women than men had stage 1 and 2 hypertension, respectively (25 vs. 35% and 14 vs. 31%, P < 0.001). During follow-up, 1.4% of women and 5.7% of men experienced incident ACS (P < 0.001). Adjusted for diabetes, smoking, body mass index, cholesterol, and physical activity, stage 1 hypertension was associated with higher risk of ACS in women [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.32–3.60], while the association was non-significant in men (HR 1.30, 95% CI 0.98–1.71). After additional adjustment for systolic and diastolic BP, respectively, stage 1 diastolic hypertension was associated with ACS in women (HR 2.79 [95% CI 1.62-4.82]), but not in men (HR 1.24 [95% CI 0.95-1.62]), while stage 1 systolic hypertension was not associated with ACS in either sex. Conclusion Among subjects in their early 40s, stage 1 hypertension was a stronger risk factor for ACS during midlife in women than in men.publishedVersio

Inflammation, sex, blood pressure changes and hypertension in midlife: the Hordaland Health Study

Our aim was to test sex-specific associations of circulating markers of inflammation with blood pressure (BP) and incident hypertension in midlife. Participants in the Hordaland Health study (n = 3280, 56% women, mean age 48 years) were examined at baseline and followed for 6 years. Circulating levels of inflammatory markers including high-sensitive C-reactive protein (hs-CRP), neopterin, and pyridoxic acid ratio (PAr) index were measured at follow-up. The associations with systolic/diastolic BP and incident hypertension were tested in sex-specific linear- or logistic-regression analyses adjusted for body mass index, serum triglycerides, creatinine, physical activity, smoking and diabetes. At follow-up, women had lower mean BP than men (124/72 vs. 130/78 mmHg, p < 0.001). Higher hs-CRP was significantly associated with greater systolic and diastolic BP (standardized β = 0.07 and β = 0.09, both p < 0.01) in women, but not in men. Higher neopterin was associated with higher diastolic BP in women and higher PAr index was associated with higher diastolic BP in women and higher systolic and diastolic BP in men (all p < 0.01). Compared to hs-CRP < 1 mg/l, higher levels of hs-CRP 1–<3 mg/l and hs-CRP ≥ 3 mg/l were associated with new-onset hypertension only in women (odds ratio (OR) 1.74, 95% CI 1.20–2.53 and OR 1.87, 95% CI 1.20–2.90). Sex-interactions were found for hs-CRP and neopterin in models on incident hypertension and diastolic BP, respectively (both p < 0.05). Higher levels of circulating markers of inflammation were associated with higher BP and incident hypertension in a sex-specific manner. Our results suggest a sex-specific interaction between cardiovascular inflammation and BP in midlife.publishedVersio

Subclinical cardiac organ damage in patients with moderate to severe psoriasis

We explored the association between subclinical cardiac organ damage (OD) with comorbidities and psoriasis severity in 53 psoriasis patients on infliximab treatment (age 47 ± 15 years, 30% women) and 99 controls without psoriasis (age 47 ± 11 years, 28% women). Cardiac OD was assessed by echocardiography as the presence of increased left ventricular (LV) relative wall thickness (RWT), LV hypertrophy or dilated left atrium. Psoriasis severity was graded using the psoriasis area and severity index (PASI). The prevalence of hypertension was 66% in psoriasis vs. 61% in controls (p = 0.54) and cardiac OD seen in 51 and 73%, respectively (p = 0.007). Psoriasis was associated with a lower prevalence of cardiac OD (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.13–0.77, p = 0.01) independent of age, sex, smoking, body mass index, and hypertension. Among psoriasis patients, hypertension was associated with increased risk of subclinical cardiac OD (OR 6.88, 95% CI 1.32–35.98, p = 0.02) independent of age, sex, and body mass index. PASI at treatment initiation was associated with a higher RWT at follow-up, independent of sex, age, and hypertension (β 0.36, p = 0.006) while no association with current PASI was found. In conclusion, cardiac OD was less prevalent in psoriasis patients on infliximab treatment than controls. Hypertension was the major covariable for subclinical cardiac OD in psoriasis

Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study

Aims Hypertension has been suggested as a stronger risk factor for acute coronary syndromes (ACS) in women than men. Whether this also applies to stage 1 hypertension [blood pressure (BP) 130–139/80–89 mmHg] is not known. Methods and results We tested associations of stage 1 hypertension with ACS in 12 329 participants in the Hordaland Health Study (mean baseline age 41 years, 52% women). Participants were grouped by baseline BP category: Normotension (BP < 130/80 mmHg), stage 1 and stage 2 hypertension (BP ≥140/90 mmHg). ACS was defined as hospitalization or death due to myocardial infarction or unstable angina pectoris during 16 years of follow-up. At baseline, a lower proportion of women than men had stage 1 and 2 hypertension, respectively (25 vs. 35% and 14 vs. 31%, P < 0.001). During follow-up, 1.4% of women and 5.7% of men experienced incident ACS (P < 0.001). Adjusted for diabetes, smoking, body mass index, cholesterol, and physical activity, stage 1 hypertension was associated with higher risk of ACS in women [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.32–3.60], while the association was non-significant in men (HR 1.30, 95% CI 0.98–1.71). After additional adjustment for systolic and diastolic BP, respectively, stage 1 diastolic hypertension was associated with ACS in women (HR 2.79 [95% CI 1.62-4.82]), but not in men (HR 1.24 [95% CI 0.95-1.62]), while stage 1 systolic hypertension was not associated with ACS in either sex. Conclusion Among subjects in their early 40s, stage 1 hypertension was a stronger risk factor for ACS during midlife in women than in men

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

Persistent cardiac organ damage in surgically and medically treated primary aldosteronism

Objective: We compared persistent cardiac organ damage in patients treated surgically or medically for primary aldosteronism. Methods: Eighty-four patients (age 57 ± 11 years, 27% women) with primary aldosteronism underwent echocardiography at time of diagnosis and after one year of treatment (49% adrenalectomy, 51% medical treatment). Persistent cardiac organ damage was defined as presence of left ventricle (LV) hypertrophy, low LV midwall shortening, global longitudinal strain and/or enlarged left atrium both at baseline and at follow-up. Results: At one year, a significant regression of LV hypertrophy was observed in surgically (44 vs. 22%, P= 0.039), but not in medically treated patients (60 vs. 51%, P = 0.206). The prevalence of enlarged left atrium was reduced in both groups (both P < 0.001), whereas systolic myocardial function remained unchanged. In multivariable logistic regression analysis, medical treatment [odds ratio (OR) 4.88 (95% confidence interval (CI) 1.26–18.88)] was a strong predictor of persistent LV hypertrophy independent of higher BMI [OR 1.20 (95% CI 1.04–1.38)] and presence of diabetes [OR 6.48 (95% CI 1.20–34.83), all P < 0.05]. Persistently low midwall shortening was associated with suppressed plasma renin after one year [OR 6.11 (95% CI 1.39–26.7)] and lower renal function [OR 0.96 (95% CI 0.94–0.99), both P < 0.05]. The strongest predictor of persistently low global longitudinal strain was higher HbA1c [OR 2.37 (95% CI 1.12–5.02), P = 0.024]. Conclusion: Persistent cardiac organ damage was more common in the medical treatment group and associated with incomplete aldosterone blockade, impaired renal function and presence of metabolic comorbidities.publishedVersio