Cardiovascular risk factors and aortic valve stenosis: towards 10-year absolute risk charts for primary prevention.

AIM: Due to aging populations the incidence of aortic valve stenosis (AVS) is increasing steeply. Since no medical therapy is available but only surgical interventions, it is highly warranted to identify modifiable risk factors for early prevention. The aim of the study was to investigate the associations of cardiovascular risk factors with AVS and to create 10-year absolute risk scores for use in primary prevention. METHODS: In the Copenhagen General Population Study (N=93,979) lifestyle data, biochemical measures, and confounders were assessed at baseline. Risk factors with the strongest association with aortic valve stenosis from Cox regression analyses were included in ten-year risk prediction models. Ten-year absolute risk scores were conducted using the method of Fine-Gray proportional sub-hazards models, accounting for competing events. RESULTS: 1,132 individuals developed AVS during follow-up. Of well-known cardiovascular risk factors, those that associated with AVS included increasing levels of remnant cholesterol, triglycerides, lipoprotein(a), systolic blood pressure, and body mass index, low adherence to Danish dietary guidelines, current smoking, high alcohol consumption, lipid-lowering therapy and diabetes mellitus. Ten-year absolute risk scores increased when compiling the most important risk factors for AVS; age, sex, body mass index, systolic blood pressure, lipoprotein(a), and diabetes. Ten-year absolute risk increased from <1% to 19%. CONCLUSIONS: The presence of cardiovascular risk factors is associated with AVS, supporting that this disease, at least partly, may be modifiable through lifestyle changes. Risk charts combining cardiovascular risk factors have the potential to identify high-risk individuals, offering opportunities for preventive strategies. (Word count 245).

This study investigates the impact of common cardiovascular risk factors on aortic valve stenosis (AVS) and introduces a risk score to predict the likelihood of developing AVS within ten years. We identified strong links between AVS and several risk factors, including lipid traits, high blood pressure, obesity, smoking, increased alcohol intake, low adherence to dietary guidelines, and diabetes. A ten-year risk score combining age, sex, body mass index, blood pressure, the lipid trait lipoprotein(a), and diabetes estimates an individual's future risk of AVS, which can range from 1% to 19%. Such risk scores enable identification of individuals at highest risk, where early prevention is most effective.

Type of Alcohol and Blood Pressure: the Copenhagen General Population Study.

BACKGROUND: Most adults ingest alcoholic beverages. Alcohol shows strong and positive associations with blood pressure (BP). We hypothesized that intake of red wine, white wine, beer, and spirits/dessert wine show similar associations with BP in the general population. METHODS: We included 104,467 males and females aged 20-100 years in the analysis of Danish general population. Alcohol use and type of alcohol were assessed by questionnaire. BP was measured by automated digital BP manometer. Multivariable linear regression models were used when analyzing association between number of drinks/week and BP, stratified by sex and adjusted for relevant confounders. Each alcohol type (red wine, white wine, beer, and spirits/dessert wine) were analyzed in similar models including adjustment for other alcohol types. RESULTS: Most people, 76,943 (73.7%) drank more than one type of alcohol. However, 12,093 (12.6%) consumed red wine only, 4,288 (4.5%) beer only, 1,815 (1.9%) white wine only, and 926 (1.0%) spirits/dessert wine only. There was a dose-response association between total drinks/week and systolic and diastolic BP (SBP, DBP) (p<0.001). The crude difference was 11 mmHg SBP and 7 mmHg DBP between high (>35 drinks/week) and low (1-2 drinks/week) alcohol intake. Overall, SBP was increased by 0.15-0.17 mmHG and DBP was increased by 0.08-0.15 mmHg per weekly drink. After stratification for age and sex, effects were slightly higher among women and among individuals were under age 60 years. CONCLUSION: Alcohol intake is associated with highly significant increased SPB and DBP. The effect is similar for red wine, white wine, beer and spirits.

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies.

OBJECTIVE: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related. RESEARCH DESIGN AND METHODS: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC. RESULTS: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (ß-coefficient: 0.02 (0.02, 0.03), p = 3 × 10- 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13)). CONCLUSIONS: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.

Iron, haemochromatosis genotypes, and risk of infections: a cohort study of 142,188 general population individuals.

It is unclear whether risk of infection is increased in individuals with hereditary haemochromatosis and in individuals with low or high plasma iron, transferrin saturation, or ferritin. Therefore, we tested whether high and low iron, transferrin saturation, and ferritin are associated with risk of infections observationally and genetically through HFE genotypes. We studied 142,188 Danish general population individuals. Iron, transferrin saturation, and ferritin were measured in 136,656, 136,599, and 38,020 individuals, respectively. HFE was genotyped for C282Y and H63D in 132,542 individuals. Median follow-up after study enrolment was 8 years(range:0-38years) for hospital and emergency room admissions with infections(n=20,394 individuals) using the National Patient Register, covering all Danish hospitals. Hazard ratios for any infection were 1.20(95%CI:1.12-1.28) and 1.14(1.07-1.22) in individuals with plasma iron≤5th or ≥95th percentile compared to individuals with iron from 26th-74th percentiles. Findings for transferrin saturation were similar, while infection risk was not increased in individuals with ferritin≤5th or ≥95th percentile. Hazard ratios in C282Y homozygotes versus non-carriers were 1.40(1.16-1.68) for any infection, 1.69(1.05-2.73) for sepsis, and 2.34(1.41-3.90) for death from infectious disease. Risk of infection was increased in C282Y homozygotes with normal plasma iron, transferrin saturation, or ferritin, and in C282Y homozygotes without liver disease, diabetes, and/or heart failure. In summary, low and high plasma iron and transferrin saturation were independently associated with increased infection risk. C282Y homozygotes had increased risk of any infection, sepsis, and death from infections. Even C282Y homozygotes with normal iron, transferrin saturation, or ferritin, not currently recommended for genotyping, had increased infection risk.

Personalized Intervention Based on Early Detection of Atherosclerosis: JACC State-of-the-Art Review.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required-moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health.

Aortic aneurysms in a general population cohort: prevalence and risk factors in men and women.

BACKGROUND AND AIMS: The prevalence and difference in risk factors for having thoracic and abdominal aortic aneurysms in men compared to women in the general population is not well-described. This study aimed to test the hypotheses i) that cardiovascular risk factors for thoracic and abdominal aortic aneurysms differ and ii) that the prevalence of thoracic and abdominal aortic aneurysms is sex specific. METHODS: Aortic examination using computed tomography angiography was performed in 11,294 individuals (56% women), with a mean age of 62 [range 40-95] years participating in the Copenhagen General Population Study. Thoracic aortic aneurysms were defined as ascending aortic diameter ≥45 mm and descending aortic diameter ≥35 mm, abdominal aortic aneurysms were defined as abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. RESULTS: Overall prevalence of aortic aneurysms in the study population included: total population 2.1%, men 4.0% and women 0.7% (p-test men vs. women p<0.001). Aortic aneurysms were independently associated with male sex, increasing age, and body surface area. While thoracic aortic aneurysms were associated with hypertension, odds ratio=2.0[95%CI:1.5-2.8], abdominal aortic aneurysms were associated with hypercholesterolemia and smoking, odds ratios=2.4[95%CI:1.6-3.6] and 3.2[95%CI:1.9-5.4]. CONCLUSIONS: Subclinical aortic aneurysms are four times more prevalent in men than women. In both sexes, increasing age and body surface area are risk factors for aortic aneurysms of any anatomical location. Whereas arterial hypertension is a risk factor for thoracic aortic aneurysms, hypercholesterolemia and smoking are risk factors for abdominal aortic aneurysms.

Prevalence of hyperthyroidism and hypothyroidism in liver transplant recipients and associated risk factors.

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05-4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43-1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Worldwide Increasing Use of Nonfasting Rather Than Fasting Lipid Profiles.

BACKGROUND: Historically, lipids and lipoproteins were measured in the fasting state for cardiovascular risk prediction; however, since 2009 use of nonfasting lipid profiles has increased substantially worldwide. For patients, nonfasting lipid profiles are convenient and avoid any risk of hypoglycemia. For laboratories, blood sampling in the morning and extra visits for patients who have not fasted are avoided. For patients, clinicians, hospitals, and society, nonfasting sampling allows same-day visits with first blood sampling followed by a short wait for test results before clinical consultation. Therefore, nonfasting compared to fasting lipid profiles will save money and time and may improve patient compliance with cardiovascular prevention programs. CONTENT: We report on the progression of endorsement and implementation of nonfasting lipid profiles for cardiovascular risk prediction worldwide and summarize the recommendations from major medical societies and health authorities in different countries. We also describe practical advantages and disadvantages for using nonfasting lipid profiles. Further, we include a description of why fasting has been the standard historically, the barriers against implementation of nonfasting lipid profiles, and finally we suggest the optimal content of a nonfasting lipid profile. SUMMARY: Lipid, lipoprotein, and apolipoprotein concentrations vary minimally in response to normal food intake and nonfasting lipid profiles are equal or superior to fasting profiles for cardiovascular risk prediction. Major guidelines and consensus statements in Europe, the United States, Canada, Brazil, Japan, India, and Australia now endorse use of nonfasting lipid profiles in some or all patients; however, there are still gaps in endorsement and implementation of nonfasting lipid profiles worldwide.

Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial.

BACKGROUND AND AIMS: The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial. METHODS: Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT. RESULTS: In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (-0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94-0.99) for a -7 mg/dL (-0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01-1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01-1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96-1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91-1.15) in the PROMINENT trial. CONCLUSIONS: Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm.

Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study.

BACKGROUND: Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction. METHODS: apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010). RESULTS: In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. CONCLUSIONS: PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.

Predicting exacerbations in COPD in the Danish general population.

BACKGROUND: Risk of exacerbations in individuals with mild chronic obstructive pulmonary disease (COPD) in the general population is less well described than in more advanced disease. We hypothesized that in addition to history of previous exacerbation also other clinical characteristics predict future moderate exacerbations. METHODS: In 96,462 individuals in the Copenhagen General Population Study, we identified 3175 with clinical COPD defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.70 and FEV1 <80% predicted in symptomatic individuals without asthma. We estimated the importance of age, sex, FEV1, modified Medical Research Council (mMRC) dyspnea scale, chronic bronchitis, exacerbation history, comorbidities, cohabitation, body mass index, smoking, and blood eosinophils for the 1-year and 3-year future risk of moderate COPD exacerbations and developed a prediction tool for future exacerbations in COPD in the general population based on easily available clinical information. RESULTS: We observed 265 exacerbations in 2543 maintenance treatment naïve individuals with COPD and 197 exacerbations in 632 individuals with COPD on maintenance treatment. In the maintenance treatment naïve group, exacerbation history (hazard ratio (HR): 8.53), low FEV1 (HR: 4.82 for <30% predicted versus 50-79% predicted), and higher age (HR: 1.46 for ≥75 years versus <65 years) were significant predictors of future exacerbations. In the group on maintenance treatment, male sex and mMRC ≥2 also predicted higher risk with borderline significance. CONCLUSIONS: In addition to exacerbation history also higher age and lower FEV1 predict future exacerbation risk in COPD in the general population.

Elevated plasma apolipoprotein E levels in people living with HIV: Associations with biomarkers and HIV-specific risk factors.

BACKGROUND AND AIMS: Apolipoprotein E (apoE) plays a crucial role in cholesterol metabolism, and high levels of apoE in plasma are associated with cardiovascular disease and all-cause mortality. We aimed to assess if HIV is independently associated with high plasma apoE and to determine HIV-related risk factors for high plasma apoE. METHODS: We included 661 people with HIV (PWH) from the Copenhagen Comorbidity in HIV (COCOMO) study with available measurement of plasma apoE. COCOMO participants were frequency matched 1:1 on age and sex with controls from the Copenhagen General Population Study. High plasma apoE was defined as levels above the 90th percentile (66.2 mg/L). The association between HIV and high plasma apoE was assessed using logistic regression models. Among PWH, both linear and logistic regression models were used to determine HIV-specific risk factors for high plasma apoE. RESULTS: Mean age was 52 years and 89 % were male. Median plasma apoE was 49.0 mg/L in PWH and 43.3 mg/L in controls, p < 0.001. HIV was associated with higher plasma apoE after adjusting for potential confounders, including triglycerides (odds ratio 2.14 [95 % CI: 1.39-3.29], p < 0.001). In PWH, higher plasma apoE was associated with a previous AIDS-defining condition in linear models before adjustment for triglycerides and integrase strand transfer inhibitor use in fully adjusted linear models. CONCLUSIONS: PWH had higher plasma apoE than controls even after adjusting for triglycerides. Further studies are needed to elucidate the clinical impact of high plasma apoE in PWH.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Elevated plasma triglycerides increase risk of psoriasis: A cohort and Mendelian randomization study.

BACKGROUND: It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to development of psoriasis, a skin disorder driven by chronic inflammation. OBJECTIVE: To determine if elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis. METHODS: Consecutive individuals from the Copenhagen General Population Study (CGPS) were included. We used plasma triglycerides (n = 108,043) and a weighted triglyceride allele score (n = 92,579) on nine known triglyceride-altering genetic variants. Genetic results were replicated in 337,159 individuals from the UK biobank. Psoriasis was ICD10-code hospital contact in main analyses, and prescription of topical antipsoriatics for mild psoriasis in sensitivity analysis. RESULTS: During a median 9.3 years (0.1-15.1) of follow-up (from 2003-2015 through 2018), 855 (1%) individuals were diagnosed with psoriasis by ICD-10 in observational analysis and 772 (1%) in Mendelian randomization analysis. In observational analysis, multivariable adjusted hazard ratio for psoriasis by ICD-10 were 1.26 (95% CI:1.15-1.39) per doubling in plasma triglycerides with a corresponding causal, genetic risk ratio of 2.10 (1.30-3.38). Causality was confirmed in the UK biobank. Results were similar but slightly attenuated when we used topical antipsoriatics prescription for mild psoriasis. CONCLUSION: Elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis.

Novel Therapies for Lipoprotein(a): Update in Cardiovascular Risk Estimation and Treatment.

PURPOSE OF REVIEW: Lipoprotein(a) is an important causal risk factor for cardiovascular disease but currently no available medication effectively reduces lipoprotein(a). This review discusses recent findings regarding lipoprotein(a) as a causal risk factor and therapeutic target in cardiovascular disease, it reviews current clinical recommendations, and summarizes new lipoprotein(a) lowering drugs. RECENT FINDINGS: Epidemiological and genetic studies have established lipoprotein(a) as a causal risk factor for cardiovascular disease and mortality. Guidelines worldwide now recommend lipoprotein(a) to be measured once in a lifetime, to offer patients with high lipoprotein(a) lifestyle advise and initiate other cardiovascular medications. Clinical trials including antisense oligonucleotides, small interfering RNAs, and an oral lipoprotein(a) inhibitor have shown great effect on lowering lipoprotein(a) with reductions up to 106%, without any major adverse effects. Recent clinical phase 1 and 2 trials show encouraging results and ongoing phase 3 trials will hopefully result in the introduction of specific lipoprotein(a) lowering drugs to lower the risk of cardiovascular disease.

Fraction of exhaled nitric oxide is higher in liver transplant recipients than in controls from the general population: a cohort study.

Background: Fraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population. Methods: FENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders. Results: The median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46-64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10-26) vs. 13 ppb (IQR 8-18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50-5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37-7.20, p = 0.007)]. Conclusion: The liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.

Normal values of myocardial blood flow measured with dynamic myocardial CT perfusion.

AIMS: Dynamic myocardial CT perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD.We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 mL/min/g and 3.58 ± 1.14 mL/min/g respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress) and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant inter-segmental differences were found (P < 0.01), which was not related to age, sex or coronary dominance. CONCLUSION: Myocardial blood flow assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex or coronary dominance. Normal values of myocardial blood flow may be helpful in the clinical evaluation of suspected myocardial ischemia using DM-CTP.

Chronic cough associated with COPD exacerbation, pneumonia and death in the general population.

Background: Chronic cough affects up to 10% of the general population and was previously perceived as a comorbidity of underlying conditions, but is nowadays classified as a disease in its own entity that could confer increased risk of morbidity and mortality. We tested the hypothesis that chronic cough is associated with increased risk of COPD exacerbation, pneumonia and all-cause mortality in the general population. Methods: We identified 2801 individuals with chronic cough, defined as cough lasting >8 weeks, among 44 756 randomly selected individuals from the Copenhagen General Population Study, and recorded COPD exacerbations, pneumonia and all-cause mortality during follow-up. Results: During up to 5.9 years of follow-up (median 3.4 years), 173 individuals experienced COPD exacerbation, 767 experienced pneumonia and 894 individuals died. Individuals with chronic cough versus those without had cumulative incidences at age 80 years of 12% versus 3% for COPD exacerbation, 30% versus 15% for pneumonia, and 25% versus 13% for death from all causes. After adjustment for age, sex and smoking, individuals with chronic cough versus those without had adjusted hazard ratios of 4.6 (95% CI 2.9-7.2) for COPD exacerbation, 2.2 (1.7-2.7) for pneumonia and 1.7 (1.4-2.0) for all-cause mortality. Among current smokers aged >60 years with airflow limitation, those with versus without chronic cough had an absolute 5-year risk of 10% versus 4% for COPD exacerbation, 16% versus 8% for pneumonia and 19% versus 12% for all-cause mortality. Conclusion: Chronic cough is associated with higher risks of COPD exacerbation, pneumonia and death, independent of airflow limitation and smoking.