Does Size Matter? Genital Self-Image, Genital Size, Pornography Use and Openness Toward Cosmetic Genital Surgery in 3503 Swedish Men and Women.

BACKGROUND: Dissatisfaction with the appearance and size of one's genitalia is a common issue, and the use of cosmetic genital surgery is increasing among people with normal genitalia. AIM: This cross-sectional study aimed to investigate the distribution of genital self-image in a large sample of males and females, and whether selected factors could predict genital self-image. METHODS: Three thousand five hundred three anonymous participants completed online questionnaires. Multiple linear regressions were used to identify the association between genital self-image and genital size (length of penis or protrusion of labia minora), consumption of sexually explicit material (SEM), sexual activity, avoidance and safety seeking behaviors, openness toward genital cosmetic surgery and age. OUTCOMES: Total scores on the Female and Male Genital Self Image Scale were used as the main outcome measures. RESULTS: Overall, 3.6% of females and 5.5% of males had a severely low genital self-image (defined as 2 SD below the mean) and 33.8% of all individuals reported dissatisfaction with the appearance of their genitalia, with 13.7% of females and 11.3% of males considering undergoing cosmetic genital surgery. Mean protrusion of labia minora and stretched flaccid penis length in the population was estimated to 0.76 cm (95% CI 0.63-0.89 cm) and 12.5 cm (95% CI 12.33-12.76 cm), respectively. A higher genital self-image score was predicted by having a larger penis or less protruding labia minora, but not by the degree of SEM consumption, although 93.6% of males and 57.5% of females had consumed SEM in the past three months. The degree of avoidance and safety seeking behaviors, sexual activity, and openness toward genital cosmetic surgery predicted a low genital self-image. Being older was associated with a better genital self-image in females. CLINICAL IMPLICATIONS: The results show that a psychological intervention may be needed as an alternative to cosmetic genital surgery for people who are dissatisfied with the appearance of their genitals. STRENGTHS AND LIMITATIONS: This is one of few available studies investigating the association between actual genital size and genital dissatisfaction. The vast sample size and high response rate are also strengths. Limitations include the cross-sectional design, and possible bias in the study sample due to self-selection. CONCLUSION: Overall, a low genital self-image and dissatisfaction with one's genitalia is relatively common and is influenced not only by genital size, but also behaviors performed to alleviate worry about one's genitals. Hustad IB, Malmqvist K, Ivanova E, et al. Does Size Matter? Genital Self-Image, Genital Size, Pornography Use and Openness Toward Cosmetic Genital Surgery in 3503 Swedish Men and Women. J Sex Med 2022;19:1378-1386.

Initial evaluation of a therapist-supported online cognitive therapy self-help for patients with taboo obsessions.

OBJECTIVES: The current study evaluated the feasibility of an internet-delivered cognitive therapy (I-CT) in a self-help format with minimal therapist support for patients with obsessive-compulsive disorder (OCD) with primary taboo obsessions. Specifically, the aims were to investigate (1) whether participants were able to grasp and apply the internet-delivered cognitive framework to their own situation; (2) whether they had clinically meaningful reductions of OCD symptom severity; and (3) whether reduced negative appraisals (hypothesized mechanism of change in CT) preceded reductions in OCD symptom severity. METHOD: Nineteen OCD patients with primary taboo obsessions, recruited from an OCD clinic or self-referrals, received the I-CT intervention for 10 weeks. I-CT did not contain any systematic exposure or response prevention. RESULTS: Adherence and engagement with the intervention was high. Most participants (n = 13, 68%) understood and successfully applied the cognitive model to their own situation. Within-group analyses showed large reductions in OCD symptom severity at post-treatment (bootstrapped within group d = 1.67 [95% CI; 0.67 to 2.66]) measured with the Yale-Brown Obsessive-Compulsive Scale. The gains were maintained at the 6-month follow-up. Post-hoc analyses revealed that the large reductions in OCD symptom severity were driven by the participants who understood the cognitive model. Reductions in negative appraisals predicted subsequent reductions in OCD symptom severity during treatment. CONCLUSION: It is possible to adapt a purely cognitive intervention to a digital guided self-help format and to achieve both cognitive change and meaningful symptom reduction. The results require confirmation in a randomized clinical trial.

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries.

BACKGROUND: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). OBJECTIVES: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex. METHODS: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and ß2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. RESULTS: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-ß2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. CONCLUSIONS: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

Reorganization of heart failure management and improved outcome - the 4D HF Project.

OBJECTIVES: Heart failure (HF) management is suboptimal in Sweden despite available evidence-based guidelines. To improve HF treatment, a comprehensive HF management program (4D project) was implemented in the Stockholm County (>2.1 million inhabitants). Design. A standardized care program centralized at five hospital-based HF clinics was implemented in 2014-2017. We registered from 2012 to 2017: (1) numbers of referrals and visits to HF clinics, (2) numbers of hospital admitted patients per million inhabitants, (3) dispensed HF medications after admission, and (4) covariate-adjusted 1-year all-cause mortality or HF readmission. Results. Yearly visits to the five HF outpatient clinics increased 3.4 times from 3,372 to 11,527. Dispensed HF drug prescriptions increased, in particular, for readmitted patients, compared to 2012 (p<.0001). Total number of hospital admitted HF patients as well as new-onset or readmitted HF patients decreased by 16, 13, and 20%, respectively (p < .0001). The combined 1-year mortality or HF readmission over the period was 48% (n = 17,124/35,880) and improved per year (HR 0.98 [0.97-0.99], p < .001) from 2012. Conclusion. A comprehensive standardized care HF management program including expanded HF clinics was associated with improved evidence-based medication, reduced HF hospitalization, and improvement of the combined outcome of 1-year mortality or HF readmission in Stockholm.

Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries.

BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD). METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age- and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses. RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-κ-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls. CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.

Personality Traits in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries.

OBJECTIVE: The purpose of this study was to describe type A behavior pattern and trait anger in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) and compare them with patients with coronary heart disease and healthy controls. Type A behavior pattern and anger have been linked to coronary heart disease in previous studies. This is the first study to assess type A behavior pattern and trait anger in MINOCA patients. METHODS: One hundred MINOCA patients, consecutively recruited during 2007-2011 at 5 coronary care units in Stockholm, were matched for sex and age to 100 coronary heart disease patients and 100 healthy controls. All participants completed the Bortner Rating Scale to quantify type A behavior pattern and the Spielberger Trait Anger Scale to quantify anger 3 months after the acute event. RESULTS: MINOCA patients' Bortner Rating Scale score was 70.9 ± 10.8 (mean ± SD) and Spielberger Trait Anger Scale score was 14 (12-17) (median; interquartile range). Coronary heart disease patients' Bortner Rating Scale score was 70.5 ± 10.2 and Spielberger Trait Anger Scale score was 14 (12-17). Healthy controls' Bortner Rating Scale score was 71.9 ± 9.1 and Spielberger Trait Anger Scale score was 13 (11-16). CONCLUSION: We found no significant differences in Bortner Rating Scale score and Spielberger Trait Anger Scale score among MINOCA, coronary heart disease patients, and healthy controls, regardless of whether total scores, subscales, or cutoffs were used to classify type A behavior pattern and trait anger. However, we cannot exclude the existence of an occasional episode of anger or mental stress in relation to the coronary event. This is the first study to assess type A behavior pattern and trait anger in patients with MINOCA, and future studies need to confirm the current findings before any firm conclusions can be made.

Prevalence of Anxiety and Depression Symptoms in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries.

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries is a working diagnosis for several heart disorders. Previous studies on anxiety and depression in patients with myocardial infarction with non-obstructive coronary arteries are lacking. Our aim was to investigate the prevalence of anxiety and depression among patients with myocardial infarction with non-obstructive coronary arteries. METHODS: We included 99 patients with myocardial infarction with non-obstructive coronary arteries together with age- and sex-matched control groups who completed the Beck Depression Inventory and the Hospital Anxiety and Depression Scale (HADS) 3 months after the acute event. RESULTS: Using the Beck Depression Inventory, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (35%) was higher than in healthy controls (9%; P = .006) and similar to that of patients with coronary heart disease (30%; P = .954). Using the HADS anxiety subscale, we found that the prevalence of anxiety in patients with myocardial infarction with non-obstructive coronary arteries (27%) was higher than in healthy controls (9%; P = .002) and similar to that of patients with coronary heart disease (21%; P = .409). Using the HADS depression subscale, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (17%) was higher than in healthy controls (4%; P = .003) and similar to that of patients with coronary heart disease (13%; P = .466). Patients with myocardial infarction with non-obstructive coronary arteries and takotsubo syndrome scored higher on the HADS anxiety subscale than those without (P = .028). CONCLUSIONS: This is the first study on the mental health of patients with myocardial infarction with non-obstructive coronary arteries to show that prevalence rates of anxiety and depression are similar to those in patients with coronary heart disease.

Plasma biomarker levels and non-obstructive coronary artery disease determined by coronary computed tomography angiography.

PURPOSE: Coronary computed tomography angiography (CTA) and several circulating biomarkers have prognostic value regarding cardiovascular disease (CVD) events, but their association is incompletely studied. We aimed to investigate whether markers of lipid metabolism, inflammation and kidney function could predict non-obstructive coronary artery disease (CAD) determined by coronary CTA, in a low-to-intermediate-risk group. METHODS: Coronary CTA and laboratory testing were performed for 115 subjects (45-70 years), with low prevalence of CVD risk factors, predominantly low-to-intermediate Framingham risk and normal or mildly reduced kidney function. RESULTS: Forty-nine (43%) had no CAD at coronary CTA, and 66 (57%) had CAD in ≥1 segment (stenosis < 50%). Adiponectin was inversely associated with CAD, and lipoprotein(a) and cystatin C were associated with CAD at coronary CTA. In multivariable logistic regression, cystatin C remained an independent predictor of CAD (OR: 2·50, 95% CI: 1·12-5·59). Cystatin C also correlated to the number of diseased segments (rs  = 0·25, P<0·01). CONCLUSION: Higher plasma levels of cystatin C were associated with non-obstructive CAD at coronary CTA in subjects with low-to-intermediate CVD risk and normal to mildly reduced kidney function.

Effect of Myocardial Infarction With Nonobstructive Coronary Arteries on Physical Capacity and Quality-of-Life.

Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA), including Takotsubo syndrome (TS), are considered to have a better survival compared with those with coronary heart disease (CHD). Studies of patients with MINOCA measuring physical and mental function including matched control groups are lacking. The aim of this study was to determine the physical capacity and quality of life in patients with MINOCA. One-hundred patients with MINOCA along with TS (25%) were investigated from 2007 to 2011. A bicycle exercise stress test was performed 6 weeks after hospitalization and QoL was investigated by the Short Form Survey 36 at 3 months' follow-up. Both a healthy and a CHD group that were age and gender matched were used as controls. The MINOCA group had a lower physical capacity (139 ± 42 W) compared with the healthy control group (167 ± 53 W, p <0.001) but better than the CHD control group (124 ± 39 W, p = 0.023). Patients with MINOCA had lower physical and mental component summary scores compared with the healthy controls (p <0.001) and lower mental component summary (p = 0.012), mental health (p = 0.016), and vitality (p = 0.008) scores compared with the CHD controls. In conclusion, the findings of this first study on exercise capacity and QoL in patients with MINOCA showed both physical and mental distress from 6 weeks to 3 months after the acute event similar to CHD controls and in some perspectives even lower scores especially in the mental component of QoL.

Risk Factors and Markers for Acute Myocardial Infarction With Angiographically Normal Coronary Arteries.

Myocardial Infarction with normal coronary arteries (MINCA) is common with a prevalence of 1% to 12% of all myocardial infarctions. The pathogenic mechanisms of MINCA are still unknown, but endothelial dysfunction has been suggested as a possible cause. To investigate risk factors and markers for MINCA, we conducted a case-control study. Considering the reported low prevalence of classical risk factors for coronary heart disease (CHD) in some but not all studies, our hypothesis was that endothelial function and intima-media thickness (IMT) were better, respectively lower, than CHD controls. One hundred patients with MINCA fulfilling diagnostic criteria according to the European Society of Cardiology/American Collage of Cardiology/American Heart Association universal definition of myocardial infarction with myocarditis excluded by cardiac magnetic resonance imaging were investigated. Risk factors, endothelial function (EndoPAT), and IMT were compared to gender- and age-matched patients with myocardial infarction and CHD, respectively healthy controls. Smoking, hypertension, impaired glucose tolerance and diabetes mellitus, inflammatory disease, and psychiatric disorders were more common in patients with MINCA than in healthy controls. In contrast to patients with CHD, the lipid profile was antiatherogenic with low low-density lipoprotein and high high-density lipoprotein cholesterol. There were no major differences between the groups regarding endothelial function and IMT that were in the normal range. In conclusion, the present study showed that MINCA was associated with many established cardiovascular risk factors without major differences in atherosclerosis markers. MINCA patients recalled a high prevalence of emotional stress before admission that together with previous psychiatric vulnerability and female gender speaks strongly in favor of Takotsubo syndrome being an important cause of MINCA.

Markers of inflammation, endothelial activation, and arterial stiffness in hypertensive heart disease and the effects of treatment: results from the SILVHIA study.

We assessed the contribution of blood pressure (BP), inflammation, and endothelial activation to the development of structural vascular and cardiac changes in hypertension. Furthermore, the effects of antihypertensive therapy were studied. We studied 114 patients with hypertension and left ventricular hypertrophy and 38 matched hypertensive subjects without cardiac hypertrophy and 38 normotensive subjects. The group with hypertension and cardiac hypertrophy were randomized to treatment with an angiotensin receptor blocker (irbesartan) or a beta-adrenergic receptor blocker (atenolol) for 48 weeks. Markers of inflammation (high-sensitive C-reactive protein, interleukin-6, leukocyte counts), vascular function (ambulatory aortic stiffness index, arterial compliance, and pulse pressure), and endothelial activation (E-selectin, intracellular adhesion molecule-1, vascular adhesion molecule-1) were assessed. Markers of inflammation and arterial stiffness were lowest in the normotensive group and highest in patients with hypertensive heart disease; endothelial markers were similar between groups. Inflammation was independently related to BP. Markers of arterial stiffness were independently related to BP and to a lesser extent to left ventricular mass. Antihypertensive treatment improved arterial compliance; inflammatory and endothelial markers remained unchanged. In conclusion, markers of inflammation and arterial stiffness are independently related to BP. Antihypertensive therapy seems to improve arterial stiffness, but effects on markers of inflammation and endothelial activation are small.

Platelet-derived microparticles during and after acute coronary syndrome.

As microparticles are shedded upon platelet activation, and may be used to assess platelet function, we measured plasma concentrations of platelet-derived microparticles (PMPs) during and after an acute coronary syndrome (ACS). Fifty-one patients with ACS were investigated at admission, within 24 hours (before coronary angiography), and six months later. Sixty-one sex- and age-matched healthy controls were investigated once. PMPs were defined as particles <1.0 µm in size, negative to phalloidin (labels cell-fragments), and positive to CD61. Exposure of phosphatidylserine (PS+), CD62P and CD142 were also measured. Plasma concentrations of PS+PMPs exposing CD61, CD62P and CD142 were elevated 2.5, 6.0-, and 5.0-fold at admission (p<0.001 for all, compared to controls; aspirin only), decreased significantly 24 hours later following initiation of treatment with clopidogrel and subcutaneous anticoagulation (p<0.001 for all), and decreased even further six months later (p<0.01 for all). However, PS+PMPs exposing CD62P or CD142 were still between 1.2-and 2.3-fold higher than in controls (p<0.001 for both). The pattern for PS-PMPs during and after the ACS was very similar to that for PS+PMPs although the numbers were approximately 1/3 lower. In conclusion, PMP concentrations follow the pattern of platelet activation during and after an ACS. Decreased concentrations are observed after initiation of antithrombotic treatment, but PMP exposing CD62P or CD142 are still elevated after six months. Flow cytometric measurements of PMP in frozen-thawed samples enable studies of platelet function in larger clinical trials.

Is fibrin formation and thrombin generation increased during and after an acute coronary syndrome?

INTRODUCTION AND METHODS: In order to study coagulation and fibrinolysis in acute coronary syndrome (ACS) we used a recently developed assay, called OH-index, which provides simultaneous measurements of fibrin formation and fibrinolysis (fibrin degradation) in the patients' plasma. We also investigated thrombin generation using the calibrated automated thrombogram (CAT), and assessed thrombin generation in vivo by measuring F1+2 plasma concentrations. In addition, to better characterize the patients we also assessed markers of inflammation and endothelial function. Eighty-seven ACS patients were sampled at admission, within 24 hours during treatment with low molecular weight heparin (LMH), and 6 months later; 65 healthy controls were also sampled. RESULTS: As assessed by OH-index fibrin formation was slightly depressed at admission, profoundly depressed during LMH treatment and comparable to controls at 6 months, whereas fibrin degradation was elevated, particularly during LMH treatment. F1+2 levels decreased during LMH treatment but did not deviate significantly from controls at admission or in convalescence. CAT data showed that peak thrombin was higher at admission and after 6 months compared to controls, whereas the endogenous thrombin potential only tended to be elevated. Both variables were strongly reduced during LMH treatment. Patients had elevated levels of markers of inflammation and endothelial function as expected. CONCLUSION: ACS-patients have an increased capacity to generate thrombin and an enhanced capacity to degrade fibrin in the acute phase. Increased thrombin generation persists also 6 months after the event.

Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).

OBJECTIVES: Hypertensive left ventricular hypertrophy (LVH) is associated with cardiomyocyte hypertrophy and an excess in myocardial collagen. Myocardial fibrosis may cause diastolic dysfunction and heart failure. Circulating levels of the carboxy-terminal propeptide of procollagen type I (PICP), an index of collagen type I synthesis, correlate with the extent of myocardial fibrosis. This study examines myocardial fibrosis in relation to blood pressure, left ventricular mass (LVM), and diastolic function. METHODS: We examined PICP levels in 115 patients with hypertensive LVH, 38 with hypertension but no hypertrophy, and 38 normotensive subjects. Patients with LVH were subsequently randomly assigned to the angiotensin II type 1 receptor blocker irbesartan or the beta1 receptor blocker atenolol for 48 weeks. Diastolic function was evaluated by tissue velocity echocardiography (n=134). We measured basal septal wall velocities of early (Em) and late (Am) diastolic myocardial wall motion, Em velocity deceleration time (E-decm), and isovolumic relaxation time (IVRTm). RESULTS: Compared with the normotensive group, PICP was elevated and left ventricular diastolic function was impaired in the hypertensive groups, with little difference between patients with and without LVH. PICP related to blood pressure, IVRTm, Em, and E/Em, but not to LVM. Irbesartan and atenolol reduced PICP similarly. Only in the irbesartan group did changes in PICP relate to changes in IVRTm, and LVM. CONCLUSION: Myocardial fibrosis and diastolic dysfunction are present in hypertension before LVH develops. The findings with irbesartan suggest a role for angiotensin II in the control of myocardial fibrosis and diastolic function in patients with hypertension with LVH.

Comparison of two immunochemical assays for measuring thrombin-activatable fibrinolysis inhibitor concentration with a functional assay in patients with acute coronary syndrome.

TAFI was measured as relative activity concentration (Pefakit) and antigen concentration (Haemochrom and Asserachrom) both acutely and during convalescence in patients suffering from acute coronary syndrome, and in a group of healthy controls. There was a rather weak but significant correlation between the activity and antigen concentrations. The results obtained by the Haemochrom method, assumed to measure the concentrations of all forms of TAFI, were lower than those by the Asserachrom method although the latter is assumed to only measure the pro-TAFI concentration. Both immunoassays gave lower results than the functional method (Pefakit). The patients in the convalescence phase showed a higher activity concentration than the healthy controls. The Asserachrom showed a higher concentration in the acute and convalescence phases of the patients compared to the controls, whereas the Haemochrom did not show any such difference. This could be related to different species of the TAFI molecule and thus different reactivity to the antibodies. Therefore the optimal choice of assay for determination of TAFI in different clinical studies is of importance. The Pefakit and Asserachrom seem to be appropriate candidates.

Tissue velocity echocardiography shows early improvement in diastolic function with irbesartan and atenolol therapy in patients with hypertensive left ventricular hypertrophy. Results form the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA).

BACKGROUND: Abnormal diastolic function is common in hypertensive left ventricular hypertrophy (LVH). Early identification and treatment may prevent future cardiovascular events. METHODS: We examined 58 hypertensive patients with LVH, 38 with hypertension but no LVH, and 38 normotensive subjects. The effects of the AT1 receptor blocker irbesartan and the beta1 blocker atenolol on diastolic function during 48 weeks of treatment were evaluated in the LVH group by tissue velocity echocardiography (TVE). We measured basal septal and lateral wall velocities of early (Em) and late (Am) diastolic myocardial wall motion, Em velocity deceleration time (E-decm), and isovolumic relaxation time (IVRTm). For comparison, diastolic function was assessed by conventional mitral pulse wave Doppler echocardiography. RESULTS: Diastolic function was impaired in both hypertensive groups. Irbesartan and atenolol (week 48, septal wall) improved IVRTm (-44%, P<.001, and -19%, P<.001; P

Irbesartan and atenolol improve diastolic function in patients with hypertensive left ventricular hypertrophy.

OBJECTIVES AND DESIGN: An abnormal diastolic filling is common in hypertensive left ventricular (LV) hypertrophy, a condition that may lead to heart failure and death. The renin-angiotensin-aldosterone system has been implicated in the development of LV hypertrophy. This study examines the effects of 48 weeks of double-blind treatment with the AT1 receptor blocker irbesartan and the beta-blocker atenolol on diastolic function. METHODS: Diastolic function was evaluated in 115 hypertensive patients with LV hypertrophy by Doppler echocardiography mitral inflow velocities calculated from the peak of early (E) and peak of late (A) diastolic velocities (E/A ratio), the E-wave deceleration time, the isovolumic relaxation time, the pulmonary venous flow velocity, and by the atrioventricular valve plane displacement method. RESULTS: By similar reductions in blood pressure both groups progressively reduced the LV mass index, with a greater reduction in the irbesartan group (P = 0.024). Diastolic function was improved similarly by irbesartan and atenolol; for example, the E/A ratio by 12 and 14% (P = 0.022 and P < 0.001), and the pulmonary venous flow velocity by 10 and 7% (P = 0.036 and P = 0.001), respectively. The isovolumic relaxation time was improved by irbesartan (P = 0.040) only, and was related to changes in LV geometry (P < 0.001). For atenolol, improvement in diastolic function was associated only with the reduction in blood pressure (P = 0.048). An improvement in diastolic function appeared greater in concentric LV hypertrophy than in eccentric LV hypertrophy. CONCLUSIONS: Treatment based on atenolol or irbesartan improves diastolic function in patients with hypertensive LV hypertrophy to the same degree, but through different mechanisms.

Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment.

BACKGROUND: Our aim was to determine whether the change in left ventricular (LV) mass in response to antihypertensive treatment could be predicted by multivariate analysis of single nucleotide polymorphisms (SNPs) in candidate genes reflecting pathways likely to be involved in blood pressure control. METHODS: Patients with mild to moderate primary hypertension and LV hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta1 adrenoreceptor blocker atenolol (n = 49). A microarray-based minisequencing system was used for genotyping 74 SNPs in 25 genes. These genotypes were related to the change in LV mass index by echocardiography, after 12 weeks treatment as monotherapy, using stepwise multiple regression analysis. RESULTS: The blood pressure reductions were similar and significant in both treatment groups. Two SNPs in two separate genes (the angiotensinogen T1198C polymorphism, corresponding to the M235T variant and the apolipoprotein B G10108A polymorphism) for those treated with irbesartan, and the adrenoreceptor alpha2A A1817G for those treated with atenolol, significantly predicted the change in LV mass. The predictive power of these SNPs was independent of the degree of blood pressure reduction. CONCLUSION: SNPs in the angiotensinogen, apolipoprotein B, and the alpha2 adrenoreceptor gene predicted the change in LV mass during antihypertensive therapy. These results illustrate the potential of using microarray-based technology for SNP genotyping in predicting individual drug responses.

Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).

BACKGROUND: Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta1 (TGF-beta1); AT1-receptor antagonists reverse these changes. The TGF-beta1 G + 915C polymorphism is associated with interindividual variation in TGF-beta1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment. HYPOTHESIS: We aimed to determine whether the TGF-beta1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT1-receptor antagonists or a beta1-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group. METHODS: We determined the association between the TGF-beta1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double-blind study to receive treatment for 48 weeks with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol. RESULTS: Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta1, responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI -44.7 g/m2 vs. -22.2 g/m2, p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group. CONCLUSIONS: The TGF-beta1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT1-receptor antagonist irbesartan.