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Background: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. Methods: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute –funded Multi-Ethnic Study of Atherosclerosis. Results: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04–1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06–1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87–1.18]). Similarly, a very high LDL-C level ( > 193 mg/dL) versus LDL-C 0 (aHR, 2.42 [95% CI, 1.59–3.67]) but not in those without CAC (aHR, 0.92 [0.48–1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. Conclusions: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

OBJECTIVES: The aim of this study was to examine prevalence, predictors, and impact of coronary artery calcium (CAC) across different risk factor burdens on the prevalence of obstructive coronary artery disease (CAD) and future coronary heart disease (CHD) risk in young patients.BACKGROUND: The interplay of risk factors and CAC for predicting CHD in young patients aged ≤45 years is not clear.METHODS: The study included 3,691 symptomatic patients (18-45 years of age) from the WDHR (Western Denmark Heart Registry) undergoing coronary computed tomographic angiography. CHD events were myocardial infarction and late revascularization.RESULTS: During a median of 4.1 years of follow-up, 57 first-time CHD events occurred. In total, 3,180 patients (86.1%) had CAC = 0 and 511 patients (13.9%) had CAC > 0. Presence of CAC increased with number of risk factors (odds ratio: 4.5 [95% CI: 2.7-7.3] in patients with >3 vs 0 risk factors). The prevalence of obstructive CAD at baseline and the rate of future CHD events increased in a stepwise manner with both higher CAC and number of risk factors. The CHD event rate was lowest at 0.5 (95% CI: 0.1-3.6) per 1,000 person-years in patients with 0 risk factors and CAC = 0. Among patients with >3 risk factors, the event rate was 3.1 (95% CI: 1.0-9.7) in patients with CAC = 0 compared with 36.3 (95% CI: 17.3-76.1) in patients with CAC >10.CONCLUSIONS: In young patients, there is a strong interplay between CAC and risk factors for predicting the presence of obstructive CAD and for future CHD risk. In the presence of risk factors, even a low CAC score is a high-risk marker. These results demonstrate the importance of assessing risk factors and CAC simultaneously when assessing risk in young patients.

Background Sitosterolaemia is a rare, autosomal recessive dyslipidaemia with increased absorption of dietary plant sterol and often presents with hypercholesterolaemia, xanthomas, and haematologic manifestations. If left untreated, sitosterolaemia can lead to high symptomatic burden and coronary artery disease (CAD). Case summary We describe a case of a young female who initially presented at 4 years of age with classic manifestations of sitosterolaemia. She was misdiagnosed and treated for both juvenile arthritis and later familial hypercholesterolaemia until adulthood, when venous blood samples showed significantly elevated concentrations of plant sterols. DNA analyses showed that the patient was homozygous for a mutation in the ABCG5 gene, [c.1336C>T, p.(Arg446*)], which is known to be associated with sitosterolaemia. Discussion Sitosterolaemia presents with multiple manifestations, which can initially be misinterpreted leading to prolonged misdiagnosis. Early diagnosis is key in order to relieve symptoms and prevent CAD.

OBJECTIVES: The authors sought to assess the distribution of 5-year risk of cardiovascular disease (CVD) events (myocardial infarction, revascularizations, ischemic stroke) and death among symptomatic patients with varying degrees of coronary artery disease (CAD) ascertained from computed tomography angiography (CTA).BACKGROUND: CTA is used increasingly as the first-line test for evaluating patients with symptoms suggestive of CAD. This creates the daily clinical challenge of best using the information available from CTA to guide appropriate downstream allocation of preventive treatments.METHODS: Among 21,275 patients from the Western Denmark Heart Registry, the authors developed a model predicting 5-year risk for CVD and death based on traditional risk factors and CAD severity. Only events occurring >90 days after CTA were included.RESULTS: During a median follow-up of 4.2 years, 1,295 CVD events and deaths occurred. The median 5-year risk for events was 4% (interquartile range: 3% to 8%), and ranged from 50% in individual patients. The degree of CAD severity was the strongest risk factor; however, traditional risk factors also contributed significantly to risk. Thus, risk distributions in patients with varying degree of CAD overlapped considerably, and patients with extensive nonobstructive CAD could have higher estimated risk than patients with obstructive CAD (stenosis >50%). Among patients with obstructive CAD, 12% had 5-year risk 20%. A similar large overlap in risk was found when revascularizations were excluded from the endpoint.CONCLUSIONS: The 5-year risk for CVD events and death varies substantially in symptomatic patients undergoing CTA, even in the presence of obstructive CAD. These results provide support for individual risk assessment to improve potential benefit when allocating preventive therapies following CTA.

OBJECTIVES: This study aimed to assess if information on CAD severity from coronary computed tomography angiography (CTA) can identify patients that benefit most from treating low-density lipoprotein-cholesterol (LDL-C) to American Heart Association/American College of Cardiology (ACC/AHA) and European Society of Cardiology (ESC) guidelines targets.BACKGROUND: Current treatment guidelines for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) disregard severity of coronary artery disease (CAD) for treatment choices. It is unclear whether severity of CAD should be considered in treatment recommendations.METHODS: Among 20,241 symptomatic patients undergoing diagnostic CTA from the Western Denmark Heart Registry, we assessed the number needed to treat (NNT) in 6 years to prevent 1 ASCVD event as well as the proportion of all events that could be prevented by treating LDL-C to targets. We assumed a 22% relative reduction of ASCVD events per 1 mmol/l reduction in LDL-C.RESULTS: In multivariable analysis with no CAD as the reference, the subdistribution hazard ratio for ASCVD events was 4.0 (95% confidence interval [CI]: 3.3 to 4.9) for 1-vessel disease, 4.6 (3.5 to 6.0) for 2-vessel disease, and 5.6 (4.0 to 8.0) for 3-vessel disease. Consequently, the NNT to prevent 1 ASCVD event in 6 years by treating LDL-C to targets varied greatly from 233 (ESC) and 110 (ACC/AHA) for patients with no CAD to 8-9 for patients with 3-vessel disease (both ACC/AHA and ESC). The estimated percentage of ASCVD events that could be prevented by achieving guideline targets was 30% to 36% for patients with obstructive disease. However, CONCLUSIONS: An individualized approach based on CAD severity can identify symptomatic patients that are likely to derive most and least benefit from treating LDL-C to ACC/AHA and ESC treatment targets.

Importance: The diagnostic value is unclear of a 0 coronary artery calcium (CAC) score to rule out obstructive coronary artery disease (CAD) and near-term clinical events across different age groups.Objective: To assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD and to assess the implications of such a CAC score and obstructive CAD across different age groups.Design, Setting, and Participants: This cohort study obtained data from the Western Denmark Heart Registry and had a median follow-up time of 4.3 years. Included patients were aged 18 years or older who underwent computed tomography angiography (CTA) between January 1, 2008, and December 31, 2017, because of symptoms that were suggestive of CAD. Data analysis was performed from April 5 to July 7, 2021.Exposures: Obstructive CAD, which was defined as 50% or more luminal stenosis.Main Outcomes and Measures: Proportion of individuals with obstructive CAD who had a CAC score of 0. Risk-adjusted diagnostic likelihood ratios were used to assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD beyond clinical variables. Risk factors associated with myocardial infarction and death were estimated.Results: A total of 23 759 symptomatic patients, of whom 12 771 (54%) had a CAC score of 0, were included. This cohort had a median (IQR) age of 58 (49-65) years and was primarily composed of women (13 160 [55%]). Overall, the prevalence of obstructive CAD was relatively low across all age groups, ranging from 3% (39 of 1278 patients) in those who were younger than 40 years to 8% (52 of 619) among those who were 70 years or older. In patients with obstructive CAD, 14% (725 of 5043) had a CAC score of 0, and the prevalence varied across age groups from 58% (39 of 68) among those who were younger than 40 years, 34% (192 of 562) among those aged 40 to 49 years, 18% (268 of 1486) among those aged 50 to 59 years, 9% (174 of 1963) among those aged 60 to 69 years, to 5% (52 of 964) among those who were 70 years or older. The added diagnostic value of a CAC score of 0 decreased at a younger age, with a risk factor-adjusted diagnostic likelihood ratio of a CAC score of 0 ranging from 0.68 (approximately 32% lower likelihood of obstructive CAD than expected) in those who were younger than 40 years to 0.18 (approximately 82% lower likelihood than expected) in those who were 70 years or older. The presence of obstructive vs nonobstructive CAD among those with a CAC score of 0 was associated with a multivariable adjusted hazard ratio of 1.51 (95% CI, 0.98-2.33) for myocardial infarction and all-cause death; however, this hazard ratio varied from 1.80 (95% CI, 1.02-3.19) in those who were younger than 60 years to 1.24 (95% CI, 0.64-2.39) in those who were 60 years or older.Conclusions and Relevance: This cohort study found that the diagnostic value of a CAC score of 0 to rule out obstructive CAD beyond clinical variables was dependent on age, with the added diagnostic value being smaller for younger patients. In symptomatic patients who were younger than 60 years, a sizable proportion of obstructive CAD occurred among those without CAC and was associated with an increased risk of myocardial infarction and all-cause death.

Dyslipidemia is a major cause of early coronary heart disease (CHD). Low-density-lipoprotein cholesterol (LDL-C), remnant cholesterol (remnant-C) and high-density lipoprotein cholesterol (HDL-C) have all been shown to be associated with risk of CHD. We aimed to compare the association of these lipid fractions with age at first myocardial infarction(MI). Design. Multicenter study of consecutive patients hospitalized with a first MI. Linear regression models were used to assess the independent association of LDL-C, remnant-C and HDL-C with age at first MI. Results. The study included 1744 patients. In univariate analyses, LDL-C, remnant-C, and HDL-C were all significantly associated with age at first MI. However, in multivariate analyses only LDL-C [−2.5 years (95%CI: −3.1 to −1.8) per 1 SD increase] and to a lesser extent remnant-C [−0.9 years (95% CI: −1.5 to −0.3)] continued to be associated with age of MI, while HDL-C [0.5 years (95%CI: −0.2 to 1.2)] was not. Conclusions. LDL-C is the lipid fraction strongest associated with younger age of presentation of first MI. These results support the importance of controlling and treating LDL-C in prevention of premature MI.

AIM: To investigate whether phase II cardiac rehabilitation (CR) conducted by a community model of shared care CR (SC-CR) including health care centres and general practice was feasible and provided acceptable results and to compare SC-CR to hospital-based CR (H-CR) in a randomised controlled trial.METHODS: Patients were randomised to H-CR or SC-CR after admission for acute coronary syndrome. In SC-CR, the general practitioner took over the responsibility of the remaining rehabilitation, pharmacological treatment and risk factor management after the initial visit to the hospital outpatient clinic. The Municipal Health Care Centres provided courses on smoking cessation, nutrition, and exercise training and contributed to disease education and psychosocial support. The main endpoint was adherence to the CR programme and compliance with lifestyle modifications.RESULTS: In total, 1364 patients were screened, 327 (24%) were eligible, and 212 (65%) accepted participation. Phase II CR was completed by 192 (91%) of the participants. Full adherence to the CR programme was seen in 53% in SC-CR versus 54% in H-CR (relative risk (RR): 0.98, 95% confidence interval: 0.73-1.32). In H-CR, patients had higher rates of adherence to dietary advice and health education. In SC-CR, 12% of patients did not attend the risk factor evaluation and clinical assessment with their general practitioner. No difference in risk factor improvement was found. Exercise training was declined by 25% in both groups.CONCLUSION: Adherence to phase II CR was high in both groups. SC-CR did not improve adherence and efficacy, but had comparable effects on medication and risk factors. Thus, SC-CR was safe and effective.

Background Changes in the organisation of chronic healthcare, an increased awareness of costs and challenges of low adherence in cardiac rehabilitation (CR) call for the exploration of more flexible CR programmes as alternatives to hospital-based CR (H-CR). A model of shared care cardiac rehabilitation (SC-CR) that included general practitioners and the municipality was developed. The aim of this study was to analyse the cost utility of SC-CR versus H-CR. Methods The cost-utility analysis was based on a randomised controlled trial of 212 patients who were allocated to SC-CR or H-CR and followed up for 12 months. A societal cost perspective was applied that included the cost of intervention, informal time, healthcare and productivity loss. Costing was based on a microcosting approach for the intervention and on national administrative registries for the other cost categories. Quality-adjusted life years (QALYs) were based on the EuroQol 5-Dimensions measurements at baseline, after 4 months and after 12 months. Conventional cost-effectiveness methodology was employed to estimate the net benefit of SC-CR. Results The average cost of SC-CR was 165.5 kDKK and H-CR 163 kDKK. Productivity loss comprised 74.1kDKK and 65.9 kDKK. SC-CR cost was an additional 2.5 kDKK (95% CI −38.1 to 43.1) ≈ (0.33; −5.1 to 5.8 k€) and a QALY gain of 0.02 (95% CI −0.03 to 0.06). The probability that SC-CR would be cost-effective was 59% for a threshold value of willingness to pay of 300 kDKK (k€40.3). Conclusion CR after shared care model and H-CR are comparable and similar in socioeconomic terms. Trial registration number NCT01522001; Results.

More than half of patients with carcinoid syndrome develop carcinoid valve disease. Both the tricuspid and pulmonary valve are often involved. Symptoms of carcinoid syndrome with flushing, diarrhea, and bronchospasm often precedes cardiac symptoms. We report a case of carcinoid initially presenting with rapid development of right heart failure due to severe pulmonary valve stenosis. In untreated carcinoid, there is a risk of carcinoid crisis with anesthesia and surgery. In local anesthesia, we performed a sub-acute balloon pulmonary valvuloplasty. The procedure was successful without any residual pulmonary valve stenosis and with immediately relief of dyspnea. The final diagnostic workup for the underlying malignancy continued the day after valvuloplasty. © 2015 Wiley Periodicals, Inc.

OBJECTIVES: Guidelines recommend initiating primary prevention with statins to those at highest cardiovascular risk. We assessed the gender-specific implementation and effectiveness of this risk-guided approach.METHODS: We identified 1399 consecutive patients without known cardiovascular disease or diabetes hospitalized with a first myocardial infarction (MI) in Denmark. Statin use before MI was assessed, and cardiovascular risk was calculated using SCORE (Systematic COronary Risk Evaluation).RESULTS: Among patients with first MI, 36% were women. Compared with men, they were older (mean 72 vs. 65years) but had a lower estimated risk (median 3.4% vs. 6.7%, SCORE high-risk model in the statin-naïve patients). Statin therapy had been initiated in 12% of women and 10% of men prior to MI. After adding 1.5mmol/L to the total cholesterol concentration of those already on statins, the estimated pre-treatment risk was much lower in women than men (median 3.8% vs. 9.2%, SCORE high-risk model), and only 29% of women would have passed the risk-based treatment threshold defined by the European guidelines (SCORE ≥5%). Estimated risk and statin use correlated directly in men but not in women. Only ~5% of first MI are prevented by the current use of statins in people without diabetes.CONCLUSION: In people destined for a first MI, statin therapy is uncommon and prevents few events. Lower-risk women receive as much statins as higher risk men. This gender disparity and inefficient targeting of statins to those at highest risk indicate that risk scoring is not widely used in routine clinical practice in Denmark.

Participation in cardiac rehabilitation (CR) is poor although CR reduces morbidity and mortality. One way in which attendance may potentially be improved is by involving municipal health-care centres (MHCC) and the patient's general practitioner (GP) to a larger degree in a model of shared care cardiac rehabilitation (SC-CR). Our study tests the feasibility of SC-CR and compares the attendance and effects of SC-CR with the individually tailored hospital-based CR (H-CR) programme.After admission for acute coronary syndrome (ACS) patients are randomized to phase II CR which is conducted either as SC-CR or H-CR. During SC-CR the patient is seen once in-hospital after which the GP takes over. MHCC supports the GP by offering educational intervention regarding smoking cessation, exercise, nutrition and mental health. A total of 208 persons hospitalised due to acute coronary syndrome are to be randomized before hospital discharge.The study aims to examine whether the organisation of SC-CR is feasible and provides the expected benefits.The trial is funded by Region Central Denmark.Clinical Trials ID: NTC 01522001.

Atherosclerotic cardiovascular disease (CVD), including acute myocardial infarction (AMI), is caused by well-known risk factors. They constitute important therapeutic targets, but their predictive value is disputed. We evaluated the effectiveness of the risk scoring system (SCORE) and thresholds for pharmacotherapy re-commended in the European guidelines on CVD prevention.The medical records of 605 consecutive patients hospitalized for a first AMI were reviewed. Patients with pre-existing CVD, diabetes, or incomplete information on risk factors were excluded. Those not treated with statin before AMI were risk stratified based on risk factors. A SCORE ≥ 5% or ≥ 10% was considered to qualify for preventive medication in young adults (age ≤ 60 years) or elderly (age60 years), respectively.Before AMI, 40 (9%) used statin. Among non-statin users, only five of the 109 young adults had a SCORE ≥ 5%, and 23 of the 284 elderly had a SCORE ≥ 10%. Among women, only three elderly qualified for treatment. More than four times more patients would have qualified for treatment with the high-risk country chart used in 2011. The incremental value of the novel high-density lipoprotein adjusted SCORE charts was limited.Few patients admitted with a first AMI used statin. Among non-statin users, SCORE and the recommended thresholds for pharmacotherapy identified no women and less than one out of ten men who untreated were destined for an AMI before 61 years of age. The preventive potential of a traditional risk factor-based health check is limited.not relevant.not relevant.

Udgivelsesdato: 2002-Dec OBJECTIVES: To evaluate changes in plasma cholesterol following health screening and health discussions in general practice. DESIGN: Randomised prospective population-based study conducted over a period of 5 years. SETTING: Primary care, all general practitioners (GPs) in a well-defined area. SUBJECTS: A random sample of inhabitants aged 30-49 years in January 1991, registered with a local GP was invited to participate. The participants (1507 persons, or 75.4% of the 2000 invited) were randomly allocated to two intervention groups and a control group. MAIN OUTCOME MEASURES: Plasma cholesterol, percentage of subjects with plasma cholesterol higher than 7 mmol/l. RESULTS: After 5 years of intervention, plasma cholesterol in the whole population was significantly lower in the intervention groups compared to the control group. The decrease was most pronounced (0.5 mmol/l) in subjects at high cardiovascular risk. The percentage of high-risk individuals with a cholesterol level higher than 7 mmol/l was significantly lower in the intervention groups compared to the control group (9.8% vs 6.2%, p = 0.04), corresponding to a 37% reduction. CONCLUSIONS: The study shows that the health checks had a measurable impact on plasma cholesterol levels, the most pronounced effect is seen among individuals at high cardiovascular risk.