Atherosclerosis. Supplements最新文献

Background and aims

Achilles tendon lesions have long been associated with genetic defects in lipid metabolism and increased risk of cardiovascular diseases (CVD). With this study we aimed to evaluate the usefulness of Achilles tendon ultrasonography in identifying people at greater risk among subjects with severe hypercholesterolemia (SH) in a high-risk population.

Methods

During the period of 2016–2017 a total of 213 participants were enrolled in this case-control study. Data of 110 patients with SH and 103 age and sex matched controls without dyslipidaeplemia and established CVD was collected.

Results

Achilles tendinopathy (AT) was present in 42.7% of subjects with SH and in 29.1% of controls (p = 0.039). Stronger association between SH and AT was seen in women – 24.1% vs 2.0% (p = 0.001). SH increased odds of AT by 1.815 (95% CI, 1.028–3.206). Prevalence of AT was higher in males despite presence (SH⁺) or absence (SH⁻) of severe hypercholesterolemia (SH⁺ 60.7% vs 24.1%, SH⁻ 55.8% vs 2.0%, p < 0.001). AT was associated with higher proportion of subjects exceeding normal mean values of TC (80.5% vs 52.9%, p = 0.001), LDL-C (76.6% vs 52.2%), TG (54.5% vs. 22.1%), ApoB (57.1% vs 22.2%), ApoE (44.0% vs 22.4%) levels and ApoB/ApoA ratio (46.1% vs 21.5%) (p = 0.001) and family history of premature coronary heart disease (CHD).

Conclusions

AT is more prevalent among subjects with SH and is associated with higher levels of TC, TG, LDL-C, ApoB, ApoE, ApoB/ApoA ratio, family history of premature CHD. SH increases the odds of developing AT.

Background and aims

Familial hypercholesterolemia (FH) is an autosomal dominant condition raising the risk of premature cardiovascular disease up to twentyfold.[1] [2] It is under-diagnosed and undertreated, in spite of availability of effective treatment. Registers are recommended to assist in the recognition and improvement of the condition since treatment reduces morbidity and mortality. Disease registers enable longitudinal review and the application of continuous quality improvement methodology. The aims of this paper are to describe the process of setting up a new FH register in Malta based on phenotype, the preliminary results achieved, the barriers encountered, how these were overcome, and future plans for development.

Methods

The registry was established as an observational clinical study designed for a small healthcare system with limited resources. Effective process design requires attention to standards, capacity, outcome measurement and feedback, which have been incorporated.

Results

43 individuals have been registered applying Dutch Lipid Clinic Network standards, including 9 Definite, 16 Probable and 18 Possible FH. Cascade testing has identified three younger, and one older FH individuals; amenable risk factors and target outcomes are available for feedback and action. Barriers included insufficient infrastructure, limited stakeholder involvement, time limitations impacting clinical care and data collection, poor recognition, awareness and referral, and limited cascade testing. Overcoming these required persistence, reorganizing clinical work, with some assistance from clinic nurses, forward planning to involve patients and raising FH awareness through presentations to various audiences.

Conclusions

During this year the register was established and is functional: awareness is being raised. Future steps will target process improvement for effectiveness and sustainability.

Aims

To investigate the status of familial hypercholesterolemia (FH) research and the characteristics of patients with FH in China.

Methods

Published papers in Chinese or English language from PubMed, SinoMed and CNKI databases from 1971 to March 2018 were searched using ‘Familial hypercholesterolemia’, ‘Chinese’ and ‘Han’ as keywords. A systematic review of studies on familial hypercholesterolemia was then conducted.

Results

A total of 391 articles were found, in which 22% were in English and 78% were in Chinese; approximately 43% are case reports and 34% are genetic reports according to the study type; 52% discussed the status of the disease and 11% investigated the subclinical status according to the study content. Furthermore, 96% of the articles were published by tertiary hospitals and 46% were conducted by cardiologists. The first expert consensus was issued in February 2018. Of the 163 case reports published before 2018, 48.7% used the Chinese FH clinical diagnostic criteria and 34.4% did not clearly indicate the diagnostic criteria. The incidence rates of low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) mutations were 82% and 9%, and proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations were rare in Chinese patients with FH. However, the data on lipid-lowering treatment rates, compliance rates and cardiovascular events in FH remain insufficient.

Conclusions

Large-scale epidemiological investigation of FH has not been demonstrated, the recognition of FH remains rudimentary, and the guidelines are incomplete in China. The diagnosis and management of Chinese FH needs to be improved.

Homozygous familial hypercholesterolemia developed into severe cardiovascular consequences early. Untreated HoFH usually cannot survive over 30 years old. Acute coronary syndrome(ACS) caused by plaque rupture is one of the main causes of death in HoFH. As the highest resolution intravascular imaging technique, optical coherence tomography(OCT) can clearly show the thickness and structural characteristics of atherosclerotic plaque caps. In this study, a Chinese male HoFH received percutaneous coronary intervention for unstable angina. After analyzed his genetic and follow-up data, OCT was performed during interventional therapy. Multiple lipid rich plaques accompanied with inflammatory cell infiltration and a thin-cap fibroatheroma(TCFA) were noted, which reflected the vulnerability of plaques. The utility of OCT had certain guiding significance for strategy of interventional therapy and the long-term drug management. And this case suggested that it was important to undergo OCT examination for patients with HoFH who required percutaneous coronary intervention.

Background and aims

Sitosterolaemia (STSL; OMIN #210250) is a disorder of lipid metabolism and a rare autosomal recessive condition caused by loss-of-function biallelic mutations in the adenosine triphosphate-binding cassette, subfamily G member 5 (ABCG5) gene (NM_022,436.2) or in the adjacent ABCG8 gene (NM_022,437.2). STSL patients often have high plasma total sterols and present a heterogeneous phenotype. Here, we describe a male patient with a post-mortem diagnosis of STSL who was admitted to the emergency department with advanced heart failure, tendon xanthomas and findings from the follow up with his living family members.

Methods

We established a family pedigree and performed whole-exome next-generation sequencing for the patient and Sanger sequencing of DNA samples obtained from his living family members. Plasma sterol (β-sitosterol) level was measured by gas chromatography/mass spectrometry.

Results

Both the patient and his younger brother carried a homozygous mutation of p. R263Q (c.788G > A) in the ABCG8 gene. The patient's plasma plant sterol level was extremely high (β-sitosterol: 107.5 μg/ml), and the plasma β-sitosterol level of his younger brother without tendon xanthomas was also abnormally high (51.5 μg/ml). The β-sitoserol levels of other living family members including ones with a heterozygous mutation of p. R263Q (c.788G > A) were normal (i.e. undetectable). Based on the results of genetic detection and very high plasma level of β-sitosterol, we made a definitive diagnosis of STSL.

Conclusions

Emergency physicians should be aware of the need to further investigate individuals with xanthomas and cardiovascular disease using biochemical and genetic analyses to aid in diagnosis and intervention.

Low-density lipoprotein (LDL) cholesterol (LDL-C) is the primary target in cardiovascular (CV) disease prevention and is commonly used in estimating CV risk; however, alternative markers may be needed when LDL-C is not an appropriate marker (e.g. in the presence of low LDL-C levels or elevated triglyceride [TG] levels). Non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) are markers of atherogenic lipoproteins with evidenced associations with CV risk and are, therefore, recommended as secondary targets, appropriate for use in the presence of elevated TG levels. The reported strength of the associations of non-HDL-C and apoB in comparison to LDL-C is conflicting between studies, potentially due to discordance of the markers which can alter their predictive pattern.

Although LDL-C levels are commonly managed with statin treatment, a residual risk of CV events still remains, and an abnormal lipid profile can persist. Combination therapy to further reduce LDL-C levels can be beneficial; a statin therapy combined with other LDL-C-lowering therapy further reduced the number of CV events. In addition, targeting other markers, including non-HDL-C, apoB, total cholesterol and TGs may also be beneficial, specifically in patients with low HDL-C and elevated TG levels. More clinical evidence is required before definitive recommendations can be made; however, a statin–fenofibrate combination demonstrated favourable reductions in major CV events in these specific patients.

Lowering low-density lipoprotein cholesterol (LDL-C) levels is associated with a well-documented reduction in cardiovascular (CV) disease (CVD) risk. Current guidelines and literature support lifestyle interventions as the primary strategy for reducing CV risk. Association of dietary modifications (such as the Mediterranean diet), physical activity and the cessation of smoking with reduced CV morbidity and mortality has been evidenced. Where lifestyle interventions are not adequate for lowering LDL-C levels and CV risk, pharmacological therapies, most commonly statins, may also be considered. The benefits of lifestyle and pharmacological interventions in the prevention of CVD are widely known, but poor adherence and persistence to these necessitate an approach that aims to improve LDL-C lowering for CVD prevention.

Nutraceuticals (targeted functional foods or dietary supplements of plant or microbial origin) are included in EU guidelines as lifestyle interventions and may provide an additional approach to controlling LDL-C levels when a pharmaceutical intervention is not (yet) indicated. However, among different nutraceuticals, the level of clinical evidence supportive of efficacy for lipid lowering needs to be considered. Meta-analyses of randomised clinical trials have demonstrated that some nutraceuticals (e.g. red yeast rice and berberine) and some nutraceutical combinations improve lipid profiles, including lowering of LDL-C, total cholesterol and triglyceride levels. Therefore, nutraceuticals may be considered in specific patient groups where there is appropriate evidence to support the efficacy and safety.

Background and aims

Hippocampal calcification is a recently described type of intracranial calcification and might be a risk factor for ischemic stroke and dementia. Data on its risk factors and insight into the etiology are limited. We aimed to investigate the association of risk factors for hippocampal calcification in two independent cohorts in the Netherlands.

Methods

Unenhanced CT scans of the brain were scored for the presence and severity of hippocampal calcification in two independent prospectively collected patient cohorts, the first consisting of aneurysmal subarachnoid hemorrhage (SAH) patients (N = 741) and the second of patients participating in the Second Manifestation of ARTerial disease (SMART) study (N = 498). We estimated the association of the risk factors age, sex, smoking, dyslipidemia, overweight, hypertension, diabetes, family history, cardiac history, cerebrovascular history, use of vitamin K antagonists and renal disease with the presence and moderate/severe calcification using logistic regression analysis.

Results

In both cohorts, age ≥60 years was associated with the presence of hippocampal calcification (odds ratio (OR) 2.47, 95% confidence interval (CI) 1.37–4.45 in SAH and OR 1.91, 95% CI 1.30–2.82 in SMART); in SMART, age was associated with moderate/severe calcification as well (OR 2.77, 96%CI 2.77 (1.36–3.65). All other risk factors, including a cumulative risk score of 5 or more risk factors, did not show any association with hippocampal calcification presence or severity.

Conclusions

We identified age as a risk factor for hippocampal calcification. All other risk factors studied were not associated with hippocampal calcification. This contradicts findings on arterial calcifications elsewhere in the body. Therefore, more research is needed to understand this discrepancy.