HDL-structure and function in relation to cardiovascular disease

Coronary heart disease (CHD) is the most common cause of death in Western societies. This disease affects both men and women and accounts for approximately 500,000 deaths annually in the U.S.A. alone. For a number of years, plasma concentration of HDL cholesterol (HDL-C) was found to correlate inversely with the incidence of coronary heart disease and atherosclerosis. In addition, other studies in humans showed that higher plasma HDL-C levels correlates with slower progression of atherosclerotic lesions and possible stabilization of unstable atherosclerotic plaque. These findings have led to the suggestion that raising HDL-C will protect from the disease. One of the first trials demonstrating the potential benefit of raising HDL-C levels was the Helsinki Heart Study. In this randomized trial, 4081 men with dyslipidemia received gemfibrozil or placebo and five years later it was seen that the drug reduced CHD risk. Gemfibrozil treatment increased HDL-C levels by 11% but also reduced total plasma cholesterol levels by 10%, LDL-C cholesterol levels by 11% and triglyceride levels by 35%. Although all fibrates have been revealed to raise HDL-C significantly, their overall effect on all-cause mortality and cardiac mortality remains debatable. More recent studies have suggested that the relationship between HDL and cardiovascular risk is more complex than first thought and extends beyond consideration of levels of total HDL-C in plasma. In particular, Mendelian randomization studies challenged the existing view on HDL-C and cardiovascular risk and prompted a discussion as to whether low HDL-C is a causal risk factor for the development of heart disease. In parallel, research interest has intensified in studies aimed at better understanding the many biological functions of HDL and the partner proteins and receptors with which it interacts. There have been a number of studies over recent years indicating that HDL can fail to function effectively in subjects at risk for coronary diseases. It is important therefore to attempt to understand if abnormalities in HDL function are associated with variation in CVD risk. This is especially true in light of the failure of recent trials that raise total HDL to reduce risk of myocardial infarction and CVD. A feature that appears to be related to the atheroprotective functions of HDL is the relative level and distribution of HDL subpopulations in different individuals. Although HDL is unusually regarded as a single entity in clinical settings, studies using non- denaturing two-dimensional electrophoresis have revealed a number of HDL particles with distinct shape, size and composition. Along the same lines, administration of statins - a medication proven to reduce CHD risk - to patients increases specific subpopulation of HDL suggesting that some of the atheroprotective properties of statins may be mediated by increasing selected HDL subpopulations. The overall objective of the present work was to examine in details the relationship of HDL oxidation potential, the ability of HDL to protect LDL from oxidation, and the abundance of the major antioxidant enzyme, PON1, to atherosclerosis in a cross section of subjects recruited from across the social economic spectrum in the West of Scotland (the pSoBid study). PSoBid is valuable as a means of testing these properties of HDL because of its mix of males and females, wide age range, and the fact that it focused in recruiting people at extremes of social deprivation with widely varying lifestyles. The population has been well characterized in terms of classical risk factors and this thesis takes the investigation to a new level of detail with respect to HDL. The major questions addressed were: 1. Is HDL oxidation (measured by three factors; time at half maximum (T1/2max), maximum velocity of oxidation (Vmax), or maximum amount of oxidized HDL measured by optical density) related to a commonly used index of atherosclerosis? 2. Is HDL antioxidant potency to protect LDL from oxidation related to its protective effect in atherosclerosis risk? 3. Is HDL PON1 activity related to atherosclerotic marker? 4. If some HDL subclasses, rather than HDL-C, are particularly related to atherosclerosis? Our major findings revealed that: 1. HDL is more readily oxidized in those subgroups associated with less atherosclerosis. 2. The susceptibility of HDL to oxidation was also related to lifestyle factors associated with less atherosclerotic disease such as moderate alcohol intake, not smoking, active exercise habit and high intake of fruits and vegetables. 3. For HDL structure, %HDL2b was inversely associated with atherosclerosis while %HDL3b was directly associated with atherosclerosis. 4. Comparing the two factors which were inversely associated with atherosclerosis, HDL oxidation and the distribution of HDL subpopulations, our results revealed that HDL oxidation potential was more important than the percentage HDL subfraction distribution in relation to atherosclerosis. 5. HDL mediated inhibition of LDL oxidation was not found to be associated with carotid atherosclerosis nor did it appear to be related to major risk factors. Our interpretation for atherosclerosis is that HDL particles, which are very abundant in the circulation, might play a sacrificial role in that they are oxidized first and therefore have the capacity to prevent LDL oxidation in vivo

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

International Impact of COVID-19 on the Diagnosis of Heart Disease

Background: The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. Objectives: The study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices. Methods: The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. Results: Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p &lt; 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth. Conclusions: COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19–related changes in care delivery is warranted

Reduction of cardiac imaging tests during the COVID-19 pandemic: The case of Italy. Findings from the IAEA Non-invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID)

Background: In early 2020, COVID-19 massively hit Italy, earlier and harder than any other European country. This caused a series of strict containment measures, aimed at blocking the spread of the pandemic. Healthcare delivery was also affected when resources were diverted towards care of COVID-19 patients, including intensive care wards. Aim of the study: The aim is assessing the impact of COVID-19 on cardiac imaging in Italy, compare to the Rest of Europe (RoE) and the World (RoW). Methods: A global survey was conducted in May–June 2020 worldwide, through a questionnaire distributed online. The survey covered three periods: March and April 2020, and March 2019. Data from 52 Italian centres, a subset of the 909 participating centres from 108 countries, were analyzed. Results: In Italy, volumes decreased by 67% in March 2020, compared to March 2019, as opposed to a significantly lower decrease (p &lt; 0.001) in RoE and RoW (41% and 40%, respectively). A further decrease from March 2020 to April 2020 summed up to 76% for the North, 77% for the Centre and 86% for the South. When compared to the RoE and RoW, this further decrease from March 2020 to April 2020 in Italy was significantly less (p = 0.005), most likely reflecting the earlier effects of the containment measures in Italy, taken earlier than anywhere else in the West. Conclusions: The COVID-19 pandemic massively hit Italy and caused a disruption of healthcare services, including cardiac imaging studies. This raises concern about the medium- and long-term consequences for the high number of patients who were denied timely diagnoses and the subsequent lifesaving therapies and procedures

Impact of COVID-19 on Diagnostic Cardiac Procedural Volume in Oceania: The IAEA Non-Invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID)

Objectives: The INCAPS COVID Oceania study aimed to assess the impact caused by the COVID-19 pandemic on cardiac procedure volume provided in the Oceania region. Methods: A retrospective survey was performed comparing procedure volumes within March 2019 (pre-COVID-19) with April 2020 (during first wave of COVID-19 pandemic). Sixty-three (63) health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, and 846 facilities outside of Oceania. The percentage change in procedure volume was measured between March 2019 and April 2020, compared by test type and by facility. Results: In Oceania, the total cardiac diagnostic procedure volume was reduced by 52.2% from March 2019 to April 2020, compared to a reduction of 75.9% seen in the rest of the world (p&lt;0.001). Within Oceania sites, this reduction varied significantly between procedure types, but not between types of health care facility. All procedure types (other than stress cardiac magnetic resonance [CMR] and positron emission tomography [PET]) saw significant reductions in volume over this time period (p&lt;0.001). In Oceania, transthoracic echocardiography (TTE) decreased by 51.6%, transoesophageal echocardiography (TOE) by 74.0%, and stress tests by 65% overall, which was more pronounced for stress electrocardiograph (ECG) (81.8%) and stress echocardiography (76.7%) compared to stress single-photon emission computerised tomography (SPECT) (44.3%). Invasive coronary angiography decreased by 36.7% in Oceania. Conclusion: A significant reduction in cardiac diagnostic procedure volume was seen across all facility types in Oceania and was likely a function of recommendations from cardiac societies and directives from government to minimise spread of COVID-19 amongst patients and staff. Longer term evaluation is important to assess for negative patient outcomes which may relate to deferral of usual models of care within cardiology