Electrocardiographic abnormalities and NT-proBNP levels at long-term follow-up of patients with dyspnea after pulmonary embolism.

OBJECTIVES: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. DESIGN: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. RESULTS: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. CONCLUSIONS: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Improved adherence to statin treatment and differences in results between men and women after pictorial risk communication-a sub-study of the VIPVIZA RCT.

BACKGROUND: People with intermediate CVD risk constitute most of the population. Within this group, the proportion of events is lower compared to the high-risk group, but they contribute with the largest absolute number of events. Atherosclerosis is a dynamic process and progression can be slowed or even reversed with medication and lifestyle changes, but adherence to prescribed treatment is crucial. AIM: To investigate the long-term effects of interventions with pictorial risk communication of cardiovascular (CVD) risk on average adherence in a group of statin users. Compare response in adherence over time between men and women after intervention. METHODS: Participants on active statin treatment were followed up to 5 years after being randomly assigned to an intervention program aimed at raising CVD risk awareness among participants and their physicians. Merging prescribed medication databases with VIPVIZA study to study adherence over time. A moving average adherence was used to compare groups. RESULTS: Generally, the average adherence to statins among the 512 participants was high. Men had a higher average adherence over time, while women had a sharper increase in adherence in conjuncture with the intervention program. CONCLUSIONS: Both men and women were receptive to pictorial information regarding CVD risk, but the intervention effect was more pronounced in women. Sex differences are important when considering risk communication strategies. Periodically repeating the intervention was beneficial for maintaining the intervention effect over time. TRIAL REGISTRATION: The VIPVIZA study is registered with ClinicalTrials.gov , May 8, 2013, number NCT01849575.

Reconstituted and frozen botulinum toxin A is as effective and safe as fresh for treating axillary hyperhidrosis: A retrospective study.

The use of reconstituted and frozen left-over botulinum toxin A, for treatment of patients with axillary hyperhidrosis seems to be common practice in healthcare. Thus, the objective of this study was to investigate the efficacy and safety of frozen and thawed versus fresh reconstituted abobotulinum toxin (Dysport®) and onabotulinum toxin (Botox®) in the treatment of axillary hyperhidrosis. A retrospective study was conducted analysing efficacy and data from pre- and 24 weeks post-treatment questionnaires together with medical records of individuals with moderate to severe axillary hyperhidrosis. The patients had received fresh prepared botulinum toxin A in their right axilla while frozen and thawed botulinum toxin A had been administered in their left axilla. Treatment was conducted at our Hyperhidrosis Clinic, Umeå University Hospital, Sweden 2019-2021. Pre- and post-treatment questionnaires from 106 patients were analysed. The patients were 18 to 55 years old, with a mean age of 30.7 ± 9.9 years. No significant differences in patient-reported variables, Hyperhidrosis Disease Severity Scale and VAS 10-point scale, were found between the different preparations (frozen compared to fresh) for abobotulinum toxin and onabotulinum toxin, before treatment and at 6 months follow-up. Multivariable regression analysis resulted in no significant difference regarding side-effects between the preparations or brands of botulinum toxin. The findings of this study support our clinical experience that both abobotulinum toxin and onabotulinum toxin, reconstituted, frozen and thawed, seem to be as effective and safe as fresh prepared botulinum toxin when treating axillary hyperhidrosis. Our findings indicate that left-over preparations of abo- and onabotulinum toxins, stored and frozen for up to 6 months, is a cost-and time-effective way of handling botulinum toxin for treatment of axillary hyperhidrosis.

Long-term sequelae following acute pulmonary embolism: A nationwide follow-up study regarding the incidence of CTEPH, dyspnea, echocardiographic and V/Q scan abnormalities.

We aimed to follow a nationwide cohort of patients with pulmonary embolism (PE) without any exclusions to generate information regarding long-term symptoms, investigational findings and to determine the prevalence of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that this approach would yield generalizable estimates of CTEPH prevalence and incidence. All individuals diagnosed with acute PE in Sweden in 2005 were identified using the National Patient Register. In 2007, survivors were asked to complete a questionnaire regarding current symptoms. Those with dyspnea were referred for further examinations with laboratory tests, electrocardiogram (ECG), and a ventilation/perfusion scan (V/Q scan). If CTEPH was suspected, a referral to the nearest pulmonary arterial hypertension-center was recommended. Of 5793 unique individuals with PE diagnosis in 2005, 3510 were alive at the beginning of 2007. Altogether 53% reported dyspnea at some degree whereof a large proportion had V/Q scans indicating mismatched defects. Further investigation revealed 6 cases of CTEPH and in parallel 18 cases were diagnosed outside this study. The overall prevalence of CTEPH was 0.4% (95% confidence interval [CI]: 0.2%-0.6%) and 0.7% (95% CI: 0.4%-1.0%) among the survivors. The cumulative incidence of CTEPH in the group of patients who underwent a V/Q scan was 1.1% (95% CI: 0.2%-2.0%). There was a high mortality following an acute PE, a high proportion of persistent dyspnea among survivors, whereof several had pathological findings on V/Q scans and echocardiography. Only a minority developed CTEPH, indicating that CTEPH is the tip of the iceberg of post-PE disturbances.

Effect of antihypertensive treatment in isolated systolic hypertension (ISH) - systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Isolated systolic hypertension (ISH) in middle-aged and elderly is associated with high cardiovascular risk, but no randomised controlled trial has assessed the effect of antihypertensive treatment in ISH using today's definition, i.e. systolic blood pressure (SBP) ≥140 mmHg and diastolic blood pressure (DBP) <90 mmHg. METHODS: A systematic review and meta-analysis of randomised controlled trials was performed. Studies with ≥1000 patient-years of follow-up, comparing more intensive versus less intensive BP targets, or active drug versus placebo, were included if the mean baseline SBP was ≥140 mmHg and the mean baseline DBP was <90 mmHg. The primary outcome was major adverse cardiovascular events (MACE). Relative risks from each trial were pooled in random-effects meta-analyses, stratified by baseline and attained SBP level. RESULTS: Twenty-four trials, including 113,105 participants (mean age 67 years; mean blood pressure 149/83 mmHg) were included in the analysis. Overall, treatment reduced the risk of MACE by 9% (relative risk 0.91, 95% confidence interval 0.88-0.93). Treatment was more effective if baseline SBP was ≥160 mmHg (RR 0.77, 95% CIs 0.70-0.86) compared to 140-159 mmHg (RR 0.92, 95% CIs 0.89-0.95; p = 0.002 for interaction), but provided equal additional benefit across all attained SBP levels (RR 0.80, 95% CIs 0.70-0.92 for <130 mmHg, RR 0.92, 95% CIs 0.89-0.96 for 130-139 mmHg, and RR 0.87, 95% CIs 0.82-0.93 for ≥140 mmHg; p = 0.070 for interaction). CONCLUSIONS: These findings support antihypertensive treatment of isolated systolic hypertension, regardless of baseline SBP, to target SBP <140 mmHg and even <130 mmHg if well tolerated.

Vascular risk profiles for predicting outcome and long-term mortality in patients with idiopathic normal pressure hydrocephalus: comparison of clinical decision support tools.

OBJECTIVE: Vascular risk factors (VRFs) may act synergistically, and clinical decision support tools (CDSTs) have been developed that present vascular risk as a summarized score. Because VRFs are a major issue in patients with idiopathic normal pressure hydrocephalus (INPH), a CDST may be useful in the diagnostic workup. The objective was to compare 4 CDSTs to determine which one most accurately predicts short-term outcome and 10-year mortality after CSF shunt surgery in INPH patients. METHODS: One-hundred forty INPH patients who underwent CSF shunt surgery were included. For each patient, 4 CDST scores (Systematic Coronary Risk Evaluation-Older Persons [SCORE-OP], Framingham Risk Score [FRS], Revised Framingham Stroke Risk Profile, and Kiefer's Comorbidity Index [KCI]) were estimated. Short-term outcome (3 months after CSF shunt surgery) was defined on the basis of improvements in gait, Mini-Mental State Examination score, and modified Rankin Scale score. The 10-year mortality rate after surgery was noted. The CDSTs were compared by using Cox regression analysis, receiver operating characteristic curve analysis, and the chi-square test. RESULTS: For 3 CDSTs, increased score was associated with increased risk of 10-year mortality. A 1-point increase in the FRS indicated a 2% higher risk of death within 10 years (HR 1.02, 95% CI 1.003-1.035, p = 0.021); SCORE-OP, 5% (HR 1.05, 95% CI 1.019-1.087, p = 0.002); and KCI, 12% (HR 1.12, 95% CI 1.03-1.219, p = 0.008). FRS predicted short-term outcome of surgery (p = 0.024). When the cutoff value was set to 32.5%, the positive predictive value was 80% and the negative predictive value was 48% (p = 0.012). CONCLUSIONS: The authors recommend using FRS to predict short-term outcome and 10-year risk of mortality in INPH patients. The study indicated that extensive treatment of the risk factors of INPH may decrease risk of mortality. Clinical trial registration no.: NCT01850914 (ClinicalTrials.gov).

Time to initiation of lipid-lowering drugs for subclinical atherosclerosis: sub-study of VIPVIZA randomized controlled trial, with single-arm cross-over.

Aims: Visual information about subclinical atherosclerosis was provided to physicians and participants in the VIPVIZA trial, inclusion 2013-16 in northern Sweden, aiming to improve adherence to cardiovascular disease (CVD) prevention guidelines. Pictorial risk information may be more actionable. The aim of this study was to investigate the effect of intervention with pictorial risk information on time to first dispensing of statins. Methods and results: Asymptomatic atherosclerotic disease was screened for by carotid ultrasound examination in 3532 participants enrolled in VIPVIZA, of those 3000 met the criteria for this study. Participants were randomly assigned to receive pictorial risk information consisting of graphical representation of atherosclerosis as compared to a control group without intervention. Time to initiation of statins was assessed during 5 years of follow-up through the National prescribed drug register. After 3 years, both groups were re-examined and received the intervention information. In the intervention group, initiation of statins increased considerably for the first 3 years and a smaller increase was also seen after re-intervention. After the cross-over, the control group showed a sharp increase in initiation of statins, almost reaching the same proportion treated at 5 years. The propensity to initiate statin treatment increased over the study period and there was no difference between men and women. Conclusions: The pictorial information had an effect on time to initiation of statins, both as original and repeated intervention and also in the control group after single-arm cross-over. The current study supports pictorial information as a tool to shorten time to initiation of statins for CVD prevention.The VIPVIZA study is registered with ClinicalTrials.gov, number NCT01849575.

Validation of the Swedish National Inpatient Register for the diagnosis of pulmonary embolism in 2005.

The Swedish National Inpatient Register (NPR) has near-complete coverage of in-hospital admissions and ICD codes in Sweden. Acute pulmonary embolism (PE) is a serious condition presenting challenges regarding diagnosis, treatment, and follow-up. Here we aimed to validate the accuracy of acute PE diagnosis in the NPR, investigational findings, antithrombotic treatment, and follow-up of PE patients in Sweden. From a nation-wide cohort of all patients with in-hospital diagnoses of acute PE (ICD-10-SE codes I26.0-I26.9) in 2005 (n = 5793), we selected those from two Swedish regions for thorough manual review of hospital records. We identified 599 patients with PE diagnoses according to the ICD-10 coding system. We excluded 58 patients with admissions related to previous PE (47; 8%) or incorrect ICD codes (11; 2%), leaving 501 patients with probable PE diagnoses. We confirmed the diagnosis in 441 (79%) cases, which was based on imaging (435 patients; 73%) or autopsy (6; 1%). In the remaining 60 (11%) cases, the PE diagnosis was based on clinical findings and can therefore not be confirmed. Of the surviving patients with PE, 231 (47%) were offered follow-up within 6 months after the acute event. At follow-up, 67 patients (29%) had symptoms requiring clinical attention (dyspnoea or reduced general condition). The Swedish NPR showed acceptable accuracy for PE diagnosis, and could be reliably used for register-based research regarding acute PE.

Survival after surgery of the ascending aorta: a matched cohort study.

OBJECTIVES: Surgery of ascending aortic aneurysms is performed prophylactically or acute. The expected survival after surgery is uncertain. The goal of this study was to compare mortality in people with aortic surgery with matched controls. METHODS: All patients undergoing ascending aortic surgery at Umeå University Hospital from 1988 to 2012, who previously participated in 1 of 3 population-based health surveys, were matched to 2 randomly selected controls from the same health survey and followed until death or until censoring on 24 August 2017, whichever came first. Mortality was calculated using the Kaplan-Meier method and the log-rank test. Cox regression analyses were made for all-cause mortality, adjusted for traditional cardiovascular risk factors. Deaths during the first 90 days after surgery and at >90 days postoperatively were studied separately. RESULTS: The median follow-up time was 9.2 years. A total of 61 of 189 patients and 51 of 370 controls died [hazard ratio (HR) 2.77, 95% confidence interval (CI) 1.91-4.01]. Mortality was increased during the first 90 days post-surgery (HR 43.4, 95% CI 5.83-323), as well as after the first 90 days (HR 1.90, 95% CI 1.25-2.88) and after acute surgery (HR 6.05, 95% CI 2.92-12.56) as well as after elective surgery (HR 2.10, 95% CI 1.35-3.27). Among 57 surgical patients with information about cause of death, 23 (40%) died of aortic disease. CONCLUSIONS: During follow-up, more patients died than matched controls. Findings were consistent when adjusting for traditional cardiovascular risk factors and across subgroups. Both short-term and long-term postoperative deaths were increased as well.

Association of education and feedback on hypertension management with risk for stroke and cardiovascular disease.

PURPOSE: Education and feedback on hypertension management has been associated with improved hypertension control. This study aimed to assess the effectiveness of such interventions to reduce the risk of stroke and cardiovascular events. MATERIALS AND METHODS: Individuals ≥18 years with a blood pressure (BP) recording in Västerbotten or Södermanland County during the study period 2001 to 2009 were included in 108 serial cohort studies, each with 24 months follow-up. The primary outcome was risk of first-ever stroke in Västerbotten County (intervention) compared with Södermanland County (control). Secondary outcomes were first-ever major adverse cardiovascular event (MACE), myocardial infarction, and heart failure, as well as all-cause and cardiovascular mortality. All outcomes were analysed using time-to-event data included in a Cox proportional hazards model adjusted for age, sex, hypertension, diabetes, coronary artery disease, atrial fibrillation, systolic BP at inclusion, marital status, and disposable income. RESULTS: A total of 121 365 individuals (mean [SD] age at inclusion 61.7 [16.3] years; 59.9% female; mean inclusion BP 142.3/82.6 mmHg) in the intervention county were compared to 131 924 individuals (63.6 [16.2] years; 61.2% female; 144.1/81.1 mmHg) in the control county. A first-ever stroke occurred in 2 823 (2.3%) individuals in the intervention county, and 3 584 (2.7%) individuals in the control county (adjusted hazard ratio 0.96, 95% CI 0.90 to 1.03). No differences were observed for MACE, myocardial infarction or heart failure, whereas all-cause mortality (HR 0.91, 95% CI 0.87 to 0.95) and cardiovascular mortality (HR 0.91, 95% CI 0.85 to 0.98) were lower in the intervention county. CONCLUSIONS: This study does not support an association between education and feedback on hypertension management to primary care physicians and the risk for stroke or cardiovascular outcomes. The observed differences for mortality outcomes should be interpreted with caution.

Do recent meta-analyses truly prove that treatment with blood pressure-lowering drugs is beneficial at any blood pressure value, no matter how low? A critical review.

Current European guidelines for the management of hypertension and on cardiovascular disease prevention place the threshold for pharmacological treatment at a SBP level of 140 mmHg or above, with the exception of patients at very high risk (mainly because of coronary heart disease). This is in agreement with the current definition of hypertension, that is, the level of blood pressure at which the benefits of treatment outweigh the risks of treatment, as documented by clinical trials. This rationale and definition was recently challenged by meta-analyses using individual participant-level data from 48 randomized trials by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC). The authors calculated for a fixed 5 mmHg pharmacological reduction of SBP an overall 10% risk reduction for major cardiovascular events. It was concluded that there was no reliable evidence of heterogeneity of treatment effects by baseline SBP categories; that the effect was independent from the presence of cardiovascular disease; applied also to old and very old individuals up to 84 years or beyond; and that BP-lowering was also beneficial in individuals with normal or high-normal SBP down to a baseline SBP less than 120 mmHg. In this report, we identify and discuss a number of shortcomings of the BPLTTC meta-analyses. In our view, the conclusions by the BPLTTC must be -together with accompanying suggestions to abandon the definition of hypertension - strongly rejected as they are not justified and may be harmful for cardiovascular health in individuals without hypertension.

Methodological Aspects of Meta-Analyses Assessing the Effect of Blood Pressure-Lowering Treatment on Clinical Outcomes.

Systematic reviews and meta-analyses are often considered the highest level of evidence, with high impact on clinical practice guidelines. The methodological literature on systematic reviews and meta-analyses is extensive and covers most aspects relevant to the design and interpretation of meta-analysis findings in general. Analyzing the effect of blood pressure-lowering on clinical outcomes poses several challenges over and above what is covered in the general literature, including how to combine placebo-controlled trials, target-trials, and comparative studies depending on the research question, how to handle the potential interaction between baseline blood pressure level, common comorbidities, and the estimated treatment effect, and how to consider different magnitudes of blood pressure reduction across trials. This review aims to address the most important methodological considerations, to guide the general reader of systematic reviews and meta-analyses within our field, and to help inform the design of future studies. Furthermore, we highlight issues where published meta-analyses have applied different analytical strategies and discuss pros and cons with different strategies.

The beneficial effect over 3 years by pictorial information to patients and their physician about subclinical atherosclerosis and cardiovascular risk: Results from the VIPVIZA randomized clinical trial.

OBJECTIVE: Non-adherence to guidelines and preventive measures is a major challenge, particularly so to obtain long-term adherence to lifestyle changes and recommended medication. The objective was to investigate if pictorial information regarding subclinical carotid atherosclerosis provided to individuals and physicians gave sustained effects on cardiovascular risk beyond the previously reported effect after 1 year and up to 3 years. METHODS: A Prospective Randomized Open Blinded End-point (PROBE) trial. Within a CVD prevention program in Västerbotten County, Sweden, 3532 healthy individuals aged 40, 50 or 60 years were enrolled and 1:1 randomized to intervention (n = 1749; pictorial information with additional prevention materials to participants and physicians) or control group (n = 1783; no pictorial information to participants and physicians). Preventive measures were managed within primary care. Participants were investigated at baseline during 2013-2016 and at follow-up after 1 and 3 years. RESULTS: A beneficial effect on cardiovascular risk was observed at 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group (p = 0.047) and SCORE was 1.69 vs. 1.82 (p = 0.022). The effect observed at 1-year was sustained over 3 years after adjustment for sex and education and more pronounced among participants with a severe atherosclerotic picture at baseline. CONCLUSIONS: This study provides evidence of sustained beneficial effects on the adherence to prevention guidelines over 3 years of pictorial information about subclinical carotid atherosclerosis, resulting in lower cardiovascular risk regardless of sex and educational level. Direct visualization of the underlying still subclinical atherosclerotic disease, rather than just indirect information about risk factors and statistical risk of future myocardial infarction, stroke and death, is one way to tackle the problem of non-adherence to prevention of cardiovascular diseases.

Prescription of Lipid-Lowering and Antihypertensive Drugs Following Pictorial Information About Subclinical Atherosclerosis: A Secondary Outcome of a Randomized Clinical Trial.

Importance: Preventive drugs are often underused. Carotid intima-media thickness and carotid plaques are associated with cardiovascular disease (CVD), and their detection could possibly improve estimation of the likelihood of CVD and prescription of preventive drugs. Objective: To evaluate whether pictorial information on participants' asymptomatic atherosclerosis based on carotid ultrasonographic examinations to participants and their physicians had an effect on prescribing of lipid-lowering or antihypertensive drugs during the following 465 days. Design, Setting, and Participants: Visualization of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention is a pragmatic randomized clinical trial nested within the Västerbotten Intervention Program, a CVD screening and prevention program in Sweden with 60% to 70% participation rates and small social selection bias. A total of 4177 individuals aged 40, 50, or 60 years participating in the Västerbotten Intervention Program who had low to moderate risk of CVD were invited to enroll in this trial from April 29, 2013, to June 7, 2016. Prescriptions for all participants were monitored for 465 days after the intervention. Data analysis was conducted from December 6, 2019, to April 2, 2020. Interventions: Participants and their family physicians were randomly assigned 1:1 to receive or not receive pictorial information from carotid ultrasonographic determination of vascular age, assessed as carotid intima-media thickness and the presence of carotid plaques, combined with a follow-up call to participants by nurses. Main Outcomes and Measures: Two outcome measures of prescriptions of antihypertensive and lipid-lowering drugs within 465 days after ultrasonography was performed. Data obtained through intention-to-treat analysis are presented as proportions of individuals with a prescription among those who had no baseline prescription for agents from these drug classes. Results: Of the 4177 individuals invited to enroll, 3532 participants were randomized and included in the analysis; 1870 (52.9%) were women, 2278 (64.5%) were aged 60 years, 978 (27.7%) were 50 years, and 276 (7.8%) were 40 years. First prescriptions of lipid-lowering drugs were higher in the intervention group vs the control group among men (118 of 639 [18.5%] vs 38 of 692 [5.5%]; P < .001) and women (126 of 804 [15.5%] vs 38 of 817 [4.7%]; P < .001). There were no significant differences in the proportion with prescription of antihypertensive drugs in the intervention vs control groups after ultrasonography among men (58 of 482 [12.0%] vs 56 of 528 [10.6%]; P = .47) and women (60 of 612 [9.8%] vs 64 of 615 [10.4%]; P = .73). Conclusions and Relevance: The findings of this trial demonstrate that provision of pictorial information on vascular age and carotid plaques based on the results of ultrasonographic examination increased physician prescription of lipid-lowering drugs but not antihypertensive drugs within the following 465 days. Trial Registration: ClinicalTrials.gov Identifier: NCT01849575.

Comparative efficacy and acceptability of different antihypertensive drug classes for cardiovascular disease prevention: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Clinical practice guidelines differ in their recommendations on first-line antihypertensive drug classes. No adequately powered randomised controlled trial have assessed all major drug classes against each other, and previous meta-analyses have mainly relied on pairwise meta-analyses for treatment comparisons. METHODS AND ANALYSIS: A systematic review and network meta-analysis will be carried out to assess the efficacy and acceptability of all major antihypertensive drug classes. PubMed and CENTRAL were searched on 21 February 2020 to identify randomised controlled trials with at least 1000 person-years of follow-up, assessing any antihypertensive agent against other agents or placebo. All trials fulfilling the inclusion criteria will be assessed for risk of bias using the second version of Cochrane's risk of bias assessment tool. The study selection process, risk of bias assessment and data extraction are done by two authors in duplicate. Relative risks from individual trials will be combined in pairwise meta-analyses; in the absence of important intransitivity, random-effects network meta-analysis will be performed. The primary outcome for efficacy will be major adverse cardiovascular events, whereas the primary acceptability outcome will be treatment discontinuation for any reason. Additional outcomes include all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, heart failure and acute renal failure. The impact of differences within drug classes will be explored through alternative networks, including analysing thiazide-like and thiazide-type diuretics separately. ETHICS AND DISSEMINATION: This review will only process aggregated study level data and does not require ethical approval. The findings will be published in a peer-reviewed medical journal. PROSPERO REGISTRATION NUMBER: CRD42020205482.

[Experiences from a multidisciplinary cardiogenetic clinic]. / Ärftliga hjärt­kärlsjukdomar ­ ett multidisciplinärt arbetssätt krävs.

Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference.  In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.

A multiple risk factor program is associated with decreased risk of cardiovascular disease in 70-year-olds: A cohort study from Sweden.

BACKGROUND: In individuals below 65 years of age, primary prevention programs have not been successful in reducing the risk of cardiovascular disease (CVD) and death. However, no large study to our knowledge has previously evaluated the effects of prevention programs in individuals aged 65 years or older. The present cohort study evaluated the risk of CVD in a primary prevention program for community-dwelling 70-year-olds. METHOD AND FINDINGS: In 2012-2017, we included 3,613 community-dwelling 70-year-olds living in Umeå, in the north of Sweden, in a health survey and multidimensional prevention program (the Healthy Ageing Initiative [HAI]). Classic risk factors for CVD were evaluated, such as blood pressure, lipid levels, obesity, and physical inactivity. In the current analysis, each HAI participant was propensity-score-matched to 4 controls (n = 14,452) from the general Swedish population using national databases. The matching variables included age, sex, diagnoses, medication use, and socioeconomic factors. The primary outcome was the composite of myocardial infarction, angina pectoris, and stroke. The 18,065 participants and controls were followed for a mean of 2.5 (range 0-6) years. The primary outcome occurred in 128 (3.5%) HAI participants and 636 (4.4%) controls (hazard ratio [HR] 0.80, 95% CI 0.66-0.97, p = 0.026). In HAI participants, high baseline levels of blood pressure and lipids were associated with subsequent initiation of antihypertensive and lipid-lowering therapy, respectively, as well as with decreases in blood pressure and lipids during follow-up. In an intention-to-treat approach, the risk of the primary outcome was lower when comparing all 70-year-olds in Umeå, regardless of participation in HAI, to 70-year-olds in the rest of Sweden for the first 6 years of the HAI project (HR 0.87, 95% CI 0.77-0.97, p = 0.014). In contrast, the risk was similar in the 6-year period before the project started (HR 1.04, 95% CI 0.93-1.17, p = 0.03 for interaction). Limitations of the study include the observational design and that changes in blood pressure and lipid levels likely were influenced by regression towards the mean. CONCLUSIONS: In this study, a primary prevention program was associated with a lower risk of CVD in community-dwelling 70-year-olds. With the limitation of this being an observational study, the associations may partly be explained by improved control of classic risk factors for CVD with the program.