Familial hypercholesterolemia (FH), a condition, which is characterized by a life-long exposure to markedly elevated low-density lipoprotein (LDL) concentrations from birth, and it still remains ...underdiagnosed and undertreated, despite the fact that its heterogeneous form represents one of the commonest genetic disorders to date. Indeed, only 10% of all estimated affected individuals have been diagnosed worldwide and for the most of them diagnosis comes too late, when atherosclerotic cardiovascular disease (ASCVD) has already been developed. Undiagnosed and undertreated FH leads to accelerated ASCVD with a high rate of premature deaths. Recently, several novel treatment modalities have been introduced, especially for the management of severe hypercholesterolemia. Nonetheless, a substantial number of FH patients still do not achieve guideline-recommended LDL cholesterol target values. In the present review we will summarize and critically discuss pitfalls and challenges in successful diagnosis and treatment of FH.Familial hypercholesterolemia (FH), a condition, which is characterized by a life-long exposure to markedly elevated low-density lipoprotein (LDL) concentrations from birth, and it still remains underdiagnosed and undertreated, despite the fact that its heterogeneous form represents one of the commonest genetic disorders to date. Indeed, only 10% of all estimated affected individuals have been diagnosed worldwide and for the most of them diagnosis comes too late, when atherosclerotic cardiovascular disease (ASCVD) has already been developed. Undiagnosed and undertreated FH leads to accelerated ASCVD with a high rate of premature deaths. Recently, several novel treatment modalities have been introduced, especially for the management of severe hypercholesterolemia. Nonetheless, a substantial number of FH patients still do not achieve guideline-recommended LDL cholesterol target values. In the present review we will summarize and critically discuss pitfalls and challenges in successful diagnosis and treatment of FH.
Abstract
Aims
Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce.
Methods and results
Systematic phenotyping of ...CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40–80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% 95% confidence interval (CI), 35.6–37.4%, 13.3% 12.6–13.9%, and 40.8% 39.9–41.7%, respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n = 9923). During a mean follow-up of 6.4 ± 1.6 years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication hazard ratio (HR) 1.46 (95% CI 1.19–1.79), P = 0. 0003. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort HR 1.51 (95% CI 1.11–2.05), P = 0.009.
Conclusion
Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities.
Graphical Abstract
Chronic venous insufficiency is highly prevalent in the general population and associated with arterial cardiovascular disease and an increased risk of all-cause mortality.
The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors ...(LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization.
This study aimed to determine if there is an increased risk of incident cardiovascular diseases (CVD) resulting from cumulative night shift work in the German population-based Gutenberg Health Study ...(GHS).
We examined working participants of the GHS at baseline and after five years. Cumulative night shift work in the 10 years before baseline was assessed and categorized as low (1-220 nights ≙ up to 1 year), middle (221-660 nights ≙ 1-3 years), and high (>660 nights ≙ more than 3 years) night shift exposure. Hazard ratios (HR) were estimated for incident "quality-assured CVD events" using Cox proportional hazard models.
At baseline, 1092 of 8167 working participants performed night shift work. During the follow-up, 202 incident cardiovascular events occurred. The crude incidence rates for CVD per 1000 person-years were 6.88 95% confidence interval (CI) 4.80-9.55 for night shift workers and 5.19 (95% CI 4.44-6.04) for day workers. Cumulative incidence curves showed a higher cumulative incidence in workers exposed to night shift work compared to day workers after five years. The adjusted HR for incident CVD events were 1.26 (95% CI 0.68-2.33), 1.37 (95% CI 0.74-2.53) and 1.19 (95% CI 0.67-2.12) for employees in the low, middle and high night shift categories compared to employees without night shift work, respectively.
The observed tendencies indicate that night shift work might be negatively associated with cardiovascular health. We expect the continued follow-up will clarify the long-term impact of night shift work.
Work-life conflicts (WLC) may impact health, but few studies prospectively consider the impact of WLC on objective outcomes such as cardiovascular disease. Using data from the Gutenberg Health Study ...(GHS), we examined if WLC at baseline was associated with an increased five-year incidence of cardiovascular events (myocardial infarct, stroke, atrial fibrillation, peripheral artery disease, coronary artery disease, chronic heart failure, sudden cardiac death). We also considered if WLC was associated with incident hypertension and arterial stiffness and if the effects of WLC on cardiovascular health differ for men and women.
A working subsample of the 15,010 GHS cohort participants completed the Copenhagen Psychosocial Questionnaire, which included five "work-privacy conflict" questions at baseline and at the five-year follow-up. Relative risks for incident hypertension due to increased WLC at baseline (WLC scores exceeding 60 out of 100) were estimated with Poisson regression in the subgroup of participants without hypertension at baseline (n = 2426). Categories of WLC at baseline and follow-up were also used to examine the risk of hypertension due to chronic/recurrent WLC. In this subgroup, we also examined the association between WLC as a continuous score ranging from 0 to 100 with change to arterial stiffness after five years using linear regression. Hazard ratios were estimated for incident cardiovascular events in a larger subsample of participants without prevalent cardiovascular disease at baseline (n = 3698) using Cox regression. We used various multivariable regression models to adjust for sex, age, socioeconomic status, occupational, household, and cardiovascular risk factors.
We found no association between WLC and incident hypertension or increased arterial stiffness. The fully-adjusted relative risk for WLC >60 at baseline and hypertension was 0.93 (95% 0.74-1.17). The risk of hypertension due to chronic/recurrent WLC >60 was increased but not statistically significant (RR = 1.13, 95% CI 0.83-1.54). Overall, hazard ratios for incident cardiovascular events were also not increased. However, stratifying the results by sex resulted in a hazard ratio of 1.47 (95% CI 0.54-3.98) for incident cardiovascular disease among women in the fully adjusted model.
Although our results were not statistically significant, they indicate that WLC is negatively impacting the cardiovascular health of women. While these results need to be confirmed with additional research and a longer follow-up, interventions to prevent WLC will promote health and could be especially beneficial for women.
Abstract Background Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed ...to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex. Methods From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out. Results A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup. Conclusions We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men. Registration https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438.
PDF
