Outcomes of Patients with Normal LDL-Cholesterol at Admission for Acute Coronary Syndromes: Lower Is Not Always Better.

BACKGROUND AND AIM: There are few prospective data on the prognostic value of normal admission low-density lipoprotein cholesterol (LDL-C) in statin-naïve patients with acute coronary syndromes (ACS) who are treated with a preemptive invasive strategy. We aimed to analyze the proportion of patients with normal LDL-C at admission for ACS in our practice, and their characteristics and clinical outcomes in comparison to patients with high admission LDL-C. PATIENTS AND METHODS: Two institutions' prospective registries of patients with confirmed ACS from Jan 2017 to Jan 2023 were used to identify 1579 statin-naïve patients with no history of prior coronary artery disease (CAD), and with available LDL-C admission results, relevant clinical and procedural data, and short- and long-term follow-up data. Normal LDL-C at admission was defined as lower than 2.6 mmol/L. All demographic, clinical, procedural, and follow-up data were compared between patients with normal LDL-C and patients with a high LDL-C level (≥2.6 mmol/L) at admission. RESULTS: There were 242 (15%) patients with normal LDL-C at admission. In comparison to patients with high LDL-cholesterol at admission, they were significantly older (median 67 vs. 62 years) with worse renal function, had significantly more cases of diabetes mellitus (DM) (26% vs. 17%), peripheral artery disease (PAD) (14% vs. 9%), chronic obstructive pulmonary disease (COPD) (8% vs. 2%), and psychological disorders requiring medical attention (19% vs. 10%). There were no significant differences in clinical type of ACS. Complexity of CAD estimated by coronary angiography was similar between the two groups (median Syntax score 12 for both groups). There were no significant differences in rates of complete revascularization (67% vs. 72%). Patients with normal LDL-C had significantly lower left ventricular ejection fraction (LVEF) at discharge (median LVEF 52% vs. 55%). Patients with normal LDL-C at admission had both significantly higher in-hospital mortality (5% vs. 2%, RR 2.07, 95% CI 1.08-3.96) and overall mortality during a median follow-up of 43 months (27% vs. 14%, RR 1.86, 95% CI 1.45-2.37). After adjusting for age, renal function, presence of diabetes mellitus, PAD, COPD, psychological disorders, BMI, and LVEF at discharge in a multivariate Cox regression analysis, normal LDL-C at admission remained significantly and independently associated with higher long-term mortality during follow-up (RR 1.48, 95% CI 1.05-2.09). CONCLUSIONS: A spontaneously normal LDL-C level at admission for ACS in statin-naïve patients was not rare and it was an independent risk factor for both substantially higher in-hospital mortality and mortality during long-term follow-up. Patients with normal LDL-C and otherwise high total cardiovascular risk scores should be detected early and treated with optimal medical therapy. However, additional research is needed to reveal all the missing pieces in their survival puzzle after ACS-beyond coronary anatomy, PCI optimization, numerical LDL-C levels, and statin therapy.

Longitudinal analysis of chest Q-SPECT/CT in patients with severe COVID-19.

INTRODUCTION: Patients with COVID-19 have an increased risk for microvascular lung thrombosis. In order to evaluate the type and prevalence of perfusion defects, we performed a longitudinal analysis of combined perfusion single-photon emission and low-dose computed tomography (Q-SPECT/CT scan) in patients with COVID-19 pneumonia. METHODS: Consecutive patients with severe COVID-19 (B.1.1.7 variant SARS-CoV-2) and respiratory insufficiency underwent chest Q-SPECT/CT during hospitalization, and 3 months after discharge. At follow-up (FU), Q-SPECT/CT were analyzed and compared with pulmonary function tests (PFT), blood analysis (CRP, D-dimers, ferritin), modified Medical Research Council (mMRC) dyspnea scale, and high-resolution CT scans (HRCT). Patients with one or more segmental perfusion defects outside the area of inflammation (PDOI) were treated with anticoagulation until FU. RESULTS: At baseline, PDOI were found in 50 of 105 patients (47.6 %). At FU, Q-SPECT/CT scans had improved significantly (p < 0.001) and PDOI were recorded in 14 of 77 (18.2 %) patients. There was a significant correlation between mMRC score and the number of segmental perfusion defects (r = 0.511, p < 0.001), and a weaker correlation with DLCO (r = -0.333, p = 0.002) and KCO (r = -0.373, p = 0.001) at FU. Neither corticosteroid therapy nor HRCT results showed an influence on Q-SPECT/CT changes (p = 0.94, p = 0.74). CRP, D-Dimers and ferritin improved but did not show any association with the FU Q-SPECT/CT results (p = 0.08). CONCLUSION: Segmental mismatched perfusion defects are common in severe COVID-19 and are correlated with the degree of dyspnea. Longitudinal analyses of Q-SPECT/CT scans in severe COVID-19 may help understand possible mechanisms of long COVID and prolonged dyspnea.

The N-Glycosylation of Total Plasma Proteins and IgG in Atrial Fibrillation.

Atrial fibrillation is a disease with a complex pathophysiology, whose occurrence and persistence are caused not only by aberrant electrical signaling in the heart, but by the development of a susceptible heart substrate. These changes, such as the accumulation of adipose tissue and interstitial fibrosis, are characterized by the presence of inflammation. N-glycans have shown great promise as biomarkers in different diseases, specifically those involving inflammatory changes. To assess the changes in the N-glycosylation of the plasma proteins and IgG in atrial fibrillation, we analyzed the N-glycosylation of 172 patients with atrial fibrillation, before and six months after a pulmonary vein isolation procedure, with 54 cardiovascularly healthy controls. An analysis was performed using ultra-high-performance liquid chromatography. We found one oligomannose N-glycan structure from the plasma N-glycome and six IgG N-glycans, mainly revolving around the presence of bisecting N-acetylglucosamine, that were significantly different between the case and control groups. In addition, four plasma N-glycans, mostly oligomannose structures and a derived trait that was related to them, were found to be different in the patients who experienced an atrial fibrillation recurrence during the six-month follow-up. IgG N-glycosylation was extensively associated with the CHA2DS2-VASc score, confirming its previously reported associations with the conditions that make up the score. This is the first study looking at the N-glycosylation patterns in atrial fibrillation and warrants further investigation into the prospect of glycans as biomarkers for atrial fibrillation.

The Global Epidemiological Transition in Cardiovascular Diseases: Unrecognised Impact of Endemic Infections on Peripheral Artery Disease.

An epidemiological transition in the prevalence of peripheral artery disease (PAD) is taking place especially in low- and middle-income countries (LMICs) where an ageing population and adoption of western lifestyles are associated with an increase in PAD. We discuss the limited evidence which suggests that infection, potentially mediated by inflammation, may be a risk factor for PAD, and show by means of an ecological analysis that country-level prevalence of the major endemic infections of HIV, tuberculosis and malaria are associated with the prevalence of PAD. While further research is required, we propose that scientists and health authorities pay more attention to the interplay between communicable and non-communicable diseases, and we suggest that limiting the occurrence of endemic infections might have some effect on slowing the epidemiological transition in PAD.

Red cell distribution width is a potent prognostic parameter for in-hospital and post-discharge mortality in hospitalized coronavirus disease 2019 patients: a registry-based cohort study on 3941 patients.

AIM: To investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission. RESULTS: The median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index). CONCLUSION: RDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.

Red Cell Distribution Width in Acute Pulmonary Embolism Patients Improves 30-Day Mortality Risk Stratification Based on the Pulmonary Embolism Severity Index.

PURPOSE: To validate red cell distribution width (RDW) as an improvement in 30-day mortality risk stratification based on the Pulmonary Embolism Severity Index (PESI) in acute pulmonary embolism (PE). PATIENTS AND METHODS: Prospective observational analysis of consecutive adult acute PE patients. RESULTS: Among 731 patients, 30-day mortality was 11.9%. With adjustment for the PESI score and number of covariates, higher RDW was associated with higher mortality (RDW continuous: OR 1.21, 95% CI 1.06-1.38; Bayesian OR 1.22, 1.07-1.40; RDW 'high' [>14.5% in men >16.1% in women] vs normal: OR 3.83, 1.98-7.46; Bayesian OR 3.98, 2.04-7.68]. Crude mortality was 3.6% if PESI 86-105 (intermediate risk), but 1.2% if RDW normal and 7.1% if RDW high; 11.8% if PESI 106-125 (high risk), but 3.6% if RDW normal and 18.8% if RDW high. Adjusted probabilities showed higher mortality (ORs between 3.5-5.8) if RDW was high in any PESI risk subgroup. Crude mortality rates in two random-split subsets (n=365 and n=366) again showed the same patterns. CONCLUSIONS: On-admission RDW above the normal range improves 30-day mortality risk stratification based on PESI score in acute PE. Particularly, it corrects PESI-based intermediate-risk or high-risk allocation by reclassification into very low-risk (<3.5%) or very high-risk (>11.0%).

Asymptomatic deep vein thromboses in prolonged hospitalized COVID-19 patients.

High incidence of venous thromboembolic (VTE) events in coronavirus disease 2019 (COVID-19) patients has been reported despite pharmacologic thromboprophylaxis. We performed prospective bilateral lower extremity ultrasound evaluation of prolonged hospitalized COVID-19 ward patients from our institution without clinical suspicion of deep vein thrombosis (DVT).A total of 102 patient were included in the study. All patients were receiving pharmacologic thromboprophylaxis, the majority in intermediate or therapeutic doses. Asymptomatic DVT was detected in 26/102 (25.5%) patients: 22 had distal and four had proximal DVT, six had bilateral leg involvement. Pulmonary embolism was highly prevalent (17/70, 24.3%) but similarly grouped among patients with and without asymptomatic DVT. In total 37.2% of patients included in the study were recognized as having VTE.Asymptomatic DVT events were more common in intensive care unit (ICU) survivors (60% in postmechanically ventilated ICU survivors, 21.2% in ward patients, 22% in high-flow oxygen treated patients; P = 0.031), in patients with higher modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk-score (median 3 vs. 2 points with and without DVT; P = 0.021) and higher body temperature on admission (median 38.7 °C vs. 37.7 °C with and without DVT; P = 0.001). No clear associations with Padua VTE risk score, demographic and other clinical characteristics, intensity of thromboprophylaxis, severity of other COVID-19 symptoms, degree of systemic inflammation or D­dimers on admission were found (P > 0.05 for all analyses).Systematic ultrasound assessment in prolonged hospitalized severe COVID-19 patients prior to hospital discharge is needed, especially in ICU survivors, to timely recognize and appropriately treat patients with asymptomatic DVT.

Effect of low-flux and high-flux dialysis membrane on plasma concentrations of cardiac troponin I.

Aim: Cardiac troponin I (cTnI) concentration stability during dialysis have not been fully elucidated. The aim is to evaluate the effect of a single dialysis session on plasma cTnI. Patients & methods: From 122 consecutive anuric adult patients (75 [61.5%] men, age 27-86 years, median 67) on chronic hemodialysis blood samples for cTnI measurement were taken before and after a dialysis. Results: Dialysis had no effect on high-flux membranes (geometric means ratio = 0.99, 0.94-1.05, df 119, t = -0.19, multiplicity adjusted p = 0.847), but cTnI levels were higher after dialysis in patients on low-flux membranes (geometric means ratio = 1.14, 1.02-1.27, df 119, t = 2.59, adjusted p = 0.021). Conclusion: Dialysis session using low-flux membranes might increase the plasma cTnI.

Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis.

BACKGROUND: Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally. METHODS: For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle-brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model. FINDINGS: We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01-6·29, vs 3·54%, 1·17-10·24, at 40-44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22-28·90, vs 12·04%, 8·67-16·60, at 80-84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97-14·77, vs 6·60%, 3·74-11·38, at 55-59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06-8·05, vs 6·37%, 4·74-8·49, at 55-59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79-8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35-13·66, vs 5·09%, 3·64-7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015. INTERPRETATION: Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future. FUNDING: None.

National and subnational estimation of the prevalence of peripheral artery disease (PAD) in China: a systematic review and meta-analysis.

BACKGROUND: Peripheral artery disease (PAD), the third leading cause of atherosclerotic vascular morbidity, affects approximately 202 million people worldwide, among whom more than two-thirds reside in low- and middle-income countries (LMIC). For China, the largest developing country, little is known about the epidemiology of PAD. We aimed to estimate the prevalence of PAD and the number of affected people in China, establish the main risk factors for PAD and assess the number of people with PAD at the sub-national level. METHODS: We searched China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline for population-based studies that have reported the prevalence of PAD in the general Chinese population from 1990 onwards. PAD was defined as an ankle-brachial index (ABI) lower than or equal to 0.90. We used a multilevel mixed-effects logistic regression to generate the gender- and age-specific prevalence of PAD, and a random-effects meta-analysis to pool the odds ratios (ORs) of major risk factors. United Nations population numbers were used to estimate and project the number of affected people from 2000 to 2020. Finally, we used the risk factors-based model to distribute the national number of people with PAD into different settings (urban and rural) and regions (East, Central and West) for the year 2010. RESULTS: Overall, 37 articles met all inclusion criteria and provided prevalence estimates, among which 14 also explored risk factors for PAD. The prevalence of PAD increased gradually by age until mid-60s, after which the increase accelerated. In males, the prevalence of PAD ranged from 2.81% (95% CI = 1.77-4.43) in those aged 25-29 years to 21.95% (95% CI = 15.39-30.31) in those 95-99 years old. In females, the PAD prevalence increased from 3.84% (95% CI = 2.44-5.98) in those aged 25-29 years to 27.95% (95% CI = 20.14-37.37) in those aged 95-99 years. The PAD prevalence was consistently higher in females than in males across all age groups. This difference was most significantly pronounced among the elderly, starting from 60 years. Between 2000 and 2020, the total number of Chinese people with PAD is expected to increase by 40%: from 29.44 million (95% CI = 22.51-38.62) in 2000 to 41.13 million (95% CI = 32.00-52.95) in 2020. Current smoking was the strongest risk factor for PAD, with a meta-odds ratio (OR) of 2.62 (95% CI = 1.44-4.76), followed by hypertension (1.94, 95% CI = 1.48-2.53) and diabetes (1.71, 95% CI = 1.45-2.01). In 2010, 15.18 million (95% CI = 11.74-19.67) people with PAD resided in the East China, 11.08 million (95% CI = 8.61-14.28) in the Central China and 8.65 million (95% CI = 6.71-11.16) in the West China. In addition, 24.20 million (95% CI = 18.82-31.16) people with PAD were living in rural areas, accounting for almost 70% of all PAD cases in China. CONCLUSIONS: With rapid ageing in China, PAD has become a serious public health problem. More research and optimal interventions on PAD are required to better identify effective strategies for prevention and treatment of PAD in China.

Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.

BACKGROUND: Lower extremity peripheral artery disease is the third leading cause of atherosclerotic cardiovascular morbidity, following coronary artery disease and stroke. This study provides the first comparison of the prevalence of peripheral artery disease between high-income countries (HIC) and low-income or middle-income countries (LMIC), establishes the primary risk factors for peripheral artery disease in these settings, and estimates the number of people living with peripheral artery disease regionally and globally. METHODS: We did a systematic review of the literature on the prevalence of peripheral artery disease in which we searched for community-based studies since 1997 that defined peripheral artery disease as an ankle brachial index (ABI) lower than or equal to 0·90. We used epidemiological modelling to define age-specific and sex-specific prevalence rates in HIC and in LMIC and combined them with UN population numbers for 2000 and 2010 to estimate the global prevalence of peripheral artery disease. Within a subset of studies, we did meta-analyses of odds ratios (ORs) associated with 15 putative risk factors for peripheral artery disease to estimate their effect size in HIC and LMIC. We then used the risk factors to predict peripheral artery disease numbers in eight WHO regions (three HIC and five LMIC). FINDINGS: 34 studies satisfied the inclusion criteria, 22 from HIC and 12 from LMIC, including 112,027 participants, of which 9347 had peripheral artery disease. Sex-specific prevalence rates increased with age and were broadly similar in HIC and LMIC and in men and women. The prevalence in HIC at age 45-49 years was 5·28% (95% CI 3·38-8·17%) in women and 5·41% (3·41-8·49%) in men, and at age 85-89 years, it was 18·38% (11·16-28·76%) in women and 18·83% (12·03-28·25%) in men. Prevalence in men was lower in LMIC than in HIC (2·89% [2·04-4·07%] at 45-49 years and 14·94% [9·58-22·56%] at 85-89 years). In LMIC, rates were higher in women than in men, especially at younger ages (6·31% [4·86-8·15%] of women aged 45-49 years). Smoking was an important risk factor in both HIC and LMIC, with meta-OR for current smoking of 2·72 (95% CI 2·39-3·09) in HIC and 1·42 (1·25-1·62) in LMIC, followed by diabetes (1·88 [1·66-2·14] vs 1·47 [1·29-1·68]), hypertension (1·55 [1·42-1·71] vs 1·36 [1·24-1·50]), and hypercholesterolaemia (1·19 [1·07-1·33] vs 1·14 [1·03-1·25]). Globally, 202 million people were living with peripheral artery disease in 2010, 69·7% of them in LMIC, including 54·8 million in southeast Asia and 45·9 million in the western Pacific Region. During the preceding decade the number of individuals with peripheral artery disease increased by 28·7% in LMIC and 13·1% in HIC. INTERPRETATION: In the 21st century, peripheral artery disease has become a global problem. Governments, non-governmental organisations, and the private sector in LMIC need to address the social and economic consequences, and assess the best strategies for optimum treatment and prevention of this disease. FUNDING: Peripheral Arterial Disease Research Coalition (Europe).

A comparison between antenatal care quality in public and private sector in rural Hebei, China.

AIM: To evaluate the quality of antenatal care (ANC) in Hebei Province and compare it between the public and private sector and within the public sector. METHODS: We conducted a Maternal, Newborn and Child Health Household Survey in 2010 using a two-stage sampling procedure and included 1079 mothers. The quality of ANC was assessed on the basis of the number of ANC visits, the time of the first ANC visit, 16 different ANC procedures, owning a maternal health care booklet, and the type of service provider. RESULTS: Almost all women (98%) received ANC services at least once, 80% at least four times, and 54% at least five times. About half of the women (46%) visited ANC facility within their first trimester. Neither public nor private sector provided all 16 standardized services, but significantly more women in public sector received ANC procedures. Most women received ANC in county or higher-level hospitals (75%) and very few in township hospitals (8%). Significantly fewer women were weighed and tested for HIV/AIDS in township than in county or higher-level hospitals. CONCLUSION: The quality of ANC in Hebei was poorer than required by China's national and World Health Organization norms. Although the public sector performed better than the private sector, the utilization and quality of care of ANC services in this sector varied and women generally visited county or higher-level health facilities.

Improving the intake of nutritious food in children aged 6-23 months in Wuyi County, China -- a multi-method approach.

AIM: To develop affordable, appropriate, and nutritious recipes based on local food resources and dietary practices that have the potential to improve infant feeding practices. METHODS: We carried out a mixed methods study following the World Health Organization's evaluation guidelines on the promotion of child feeding. We recruited caregivers with children aged 6-23 months in Wuyi County, Hebei Province, China. The study included a 24-hour dietary recall survey, local food market survey, and development of a key local food list, food combinations, and recipes. Mothers tested selected recipes at their homes for two weeks. We interviewed mothers to obtain their perceptions on the recipes. RESULTS: The 24-hour dietary recall survey included 110 mothers. Dietary diversity was poor; approximately 10% of children consumed meat and only 2% consumed vitamin A-rich vegetables. The main reason for not giving meat was the mothers' belief that their children could not chew and digest meat. With the help of mothers, we developed six improved nutritious recipes with locally available and affordable foods. Overall, mothers liked the recipes and were willing to continue using them. CONCLUSIONS: This is the first study using a systematic evidence-based method to develop infant complementary recipes that can address complementary feeding problems in China. We developed recipes based on local foods and preparation practices and identified the barriers that mothers faced toward feeding their children with nutritious food. To improve nutrition practices, it is important to both give mothers correct feeding knowledge and assist them in cooking nutritious foods for their children based on locally available products. Further research is needed to assess long-term effects of those recipes on the nutritional status of children.

Giant right coronary artery aneurysm.

Coronary artery aneurysm (CAA) is defined as dilatation of the coronary artery that is more than 1.5 times the diameter of normal adjacent segments. A coronary artery with a diameter more than 2 cm is termed as 'giant aneurysm' and only a few cases have been described in the literature. In adults, CAA is predominantly atherosclerotic in origin; however, other causes include Kawasaki disease, autoimmune disease, trauma, infection, dissection, congenital malformation and angioplasty. Clinical presentation, prognosis and management of a giant CAA are not well defined due to limited experience. We present the case of a patient with giant aneurysm of the proximal segment of the right coronary artery.

Percutaneous coronary intervention of an anomalous right coronary artery originating from the left coronary artery.

Anomalous origin of the right coronary artery is a rare congenital anomaly that was first described in 1948 by White and Edwards. It is well established that an anomalous origin of the right coronary artery can lead to angina pectoris, myocardial infarction, or sudden death, in the absence of atherosclerosis. Thus from the literature data it has been also suggested that the abnormal origin and course of anomalous coronary arteries could make them more prone to atherosclerosis due to altered flow patterns. We report our experience involving one patient who had significant atherosclerotic disease and was successfully treated with percutaneous coronary intervention (PCI) and stent implantation in an anomalous right coronary artery arising from the left coronary artery.

Interactions between genetic variants in glucose transporter type 9 (SLC2A9) and dietary habits in serum uric acid regulation.

AIM: To investigate possible interactions between genetic variants in glucose transporter type 9 (SLC2A9) gene and dietary habits in serum uric acid regulation. METHODS: Participants for this study were recruited from two isolated Croatian island communities of Vis (n=918) and Korcula (n=898). Three single nucleotide polymorphisms (SNP) from the SLC2A9 gene (rs1014290, rs6449213, rs737267) were correlated with dietary habits and uric acid. RESULTS: A significant decrease in uric acid levels was recorded with increasing consumption of milk, sour cream, duck and turkey, and eggs. The only significant interaction was found between potato consumption and rs737267 and a near-significant interaction was found between soft drinks and rs1014290 (interaction P=0.068). Increased consumption of soft drinks interacting with the TT genotype at rs1014290 increased serum uric acid. No significant interactions were observed between food products consumption and rs6449213. CONCLUSION: There is a certain extent of interaction between SLC2A9 and dietary patterns in serum uric acid determination. The metabolic effect of soft drinks seems to be determined by the underlying genotype of rs1014290.

Genome-wide association study of biochemical traits in Korcula Island, Croatia.

AIM: To identify genetic variants underlying biochemical traits--total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, albumin, and fibrinogen, in a genome-wide association study in an isolated population where rare variants of larger effect may be more easily identified. METHODS: The study included 944 adult inhabitants of the island of Korcula, as a part of larger DNA-based genetic epidemiological study in 2007. Biochemical measurements were performed in a single laboratory with stringent internal and external quality control procedures. Examinees were genotyped using Human Hap370CNV chip by Illumina, with a genome-wide scan containing 346027 single nucleotide polymorphisms (SNP). RESULTS: A total of 31 SNPs were associated with 7 investigated traits at the level of P<1.00 x 10(-5). Nine of SNPs implicated the role of SLC2A9 in uric acid regulation (P=4.10 x 10(-6)-2.58 x 10(-12)), as previously found in other populations. All 22 remaining associations fell into the P=1.00 x 10(-5)-1.00 x 10(-6) significance range. One of them replicated the association between cholesteryl ester transfer protein (CETP) and HDL, and 7 associations were more than 100 kilobases away from the closest known gene. Nearby SNPs, rs4767631 and rs10444502, in gene kinase suppressor of ras 2 (KSR2) on chromosome 12 were associated with LDL cholesterol levels, and rs10444502 in the same gene with total cholesterol levels. Similarly, rs2839619 in gene PBX/knotted 1 homeobox 1 (PKNOX1) on chromosome 21 was associated with total and LDL cholesterol levels. The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen. CONCLUSION: Although this study was underpowered for most of the reported associations to reach formal threshold of genome-wide significance under the assumption of independent multiple testing, replications of previous findings and consistency of association between the identified variants and more than one studied trait make such findings interesting for further functional follow-up studies. Changed allele frequencies in isolate population may contribute to identifying variants that would not be easily identified in much larger samples in outbred populations.

Historic, demographic, and genetic evidence for increased population frequencies of CCR5Delta32 mutation in Croatian Island isolates after lethal 15th century epidemics.

AIM: To assess the frequency of 32 base pair deletion in CCR5 (CCR5Delta32), which has been shown to confer resistance to HIV infection in a homozygous form, in 10 isolated island communities of Dalmatia, Croatia, with different histories of exposure to epidemics during and since the medieval period. METHODS: In 2002, DNA analysis of 100 randomly selected individuals from each of the 10 isolated communities of 5 Croatian islands (Susak, Rab, Vis, Lastovo, and Mljet) showed high levels of 3-generational endogamy, indicating limited gene flow. Five of the communities were decimated by epidemics of unknown cause between 1449-1456, while the other 5 villages remained unaffected. Genotyping of the CCR5 gene was performed using the polymerase chain reaction method with primers flanking the region containing 32-bp deletion. RESULTS: The frequency of CCR5Delta32 in the 5 villages affected by the epidemic was 6.1-10.0%, and 1.0-3.8% in the 5 unaffected villages. The Delta32 mutation was found in 71 of 916 alleles among the individuals from the affected villages (7.5%), and in 24 of 968 alleles in unaffected villages (2.5%, chi(2)=27.3, P<10-6). A previous study in 303 random Croatian blood donors showed the frequency of the CCR5 Delta32 of 7.1% in the general population. The difference remained significant after correcting for population structure using both STRAT and STRUCTURE software and the genomic control test, to ensure results do not arise from the background genetic differences. CONCLUSION: Our results and historical evidence, suggest that the mid-15th century epidemic could have acted as a selection pressure for the CCR5Delta32 mutation.