Adam Hartley

Trends in Mortality From Ischemic Heart Disease and Cerebrovascular Disease in Europe: 1980 to 2009.

Background— Trends in cardiovascular mortality across Europe demonstrate significant geographical variation, and an understanding of these trends has a central role in global public health. Methods and Results— Ischemic heart disease and cerebrovascular disease age-standardized death rates (as per International Classification of Diseases, ninth and tenth revisions) were collated from the World Health Organization mortality database for member states of the European Union. Trends were characterized by using Joinpoint regression analysis. An overall trend for reduction in ischemic heart disease mortality was observed, most pronounced in Western Europe (>60% for the Netherlands, United Kingdom, and Ireland) for both sexes from 1980 to 2009. Eastern European states, Romania, Croatia, and Slovakia, had modest mortality reductions. Most recently (2009), Lithuania had the highest mortality for males and females (318.1/100 000 and 166.1/100 000, respectively), followed by Latvia and Slovakia. France had the lowest mortality: 39.8/100 000 for males and 14.7/100 000 for females. Analysis of cerebrovascular disease mortality revealed that Austria had the largest reduction for both sexes (76.8% males, 76.5% females) from 1980 to 2009. The smallest improvement over this period was seen in Lithuania, Poland, and Cyprus (–5% to +20% approximately). France has the lowest present-day cerebrovascular disease mortality for both males and females (23.9/100 000 and 17.3/100 000, respectively). Conclusions— There is a growing disparity in cardiovascular mortality between Western and Eastern Europe, for which diverse explanations are discussed. The need for population-wide health promotion and primary prevention policies is emphasized.

Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy,

We provide an up-to-date overview of current topics surrounding oxidized low-density lipoprotein (oxLDL) and its related antibodies in the quest to better identify the individuals at risk of cardiovascular disease and atherosclerotic plaques with unfavorable characteristics. We discuss the potential of oxLDL and anti-oxLDL antibodies as serum biomarkers of cardiovascular disease and emerging studies examining the targeting of arterial oxLDL for imaging and therapeutic delivery.

Markers of Apoptosis Predict Cardiovascular Outcomes and Point to ‘Response to Injury’ as a Common Pathway Leading to Diabetes and Cardiovascular Events

Metabolic stress, chronic vascular injury and cellular apoptosis are include either proteolytic cleavage or the budding off of membrane miconsidered as instrumentally connected in the pathogenesis of atherosclerosis and diabetes (Gistera and Hansson, 2017). The work from Mattisson et al. (Mattisson et al., 2017) sheds light on this potentially important pathway linking cell-mediated death and cardiovascular outcomes. The study spans translational science, fromdescribing an elegant laboratory technique using Fas ligand to induce apoptosis in peripheral blood mononuclear cells and demonstrating release of TNF receptor 1 (TNFR-1), TNF-related apoptosis-inducing ligand receptor 2 (TRAILR-2) and Fas, to studying the cell death receptor plasma levels in a large well-characterized prospective population. The initial experiment demonstrated the link between ligandinduced apoptosis in cells, and the release of soluble receptors for Fas, TNFR-1 and TRAILR-2 in vitro, thus justifying the future measurement of levels of soluble receptors as clinical biomarkers relating to apoptosis. The authors took the study forward in a subset of the Malmo Diet and Cancer Study (Berglund et al., 1993), with an impressive follow up period. This part of the study demonstrated that several cardiovascular classical risk factors (age, high body mass index, smoking and hypertension) as well as high triglycerides and low levels of high density lipoprotein, correlated with the studied markers of death receptor-activated apoptosis. Furthermore, the highest tertiles for all three soluble cellular death markers predicted which patients would go on to develop diabetes, with TRAILR-2 having an independent association after correction for other risk factors. In addition, patients with known diabetes exhibited raised levels of markers of receptoractivated apoptosis. Aside frompredicting incident diabetes, the highest levels of TRAILR-2 also independently predicted future cardiovascular death, incident myocardial infarction and stroke. It has become clear that metabolic risk factors and other exogenous causes of cellular stress lead to detrimental clinical events via multiple pathways (Ceriello and Motz, 2004). This paper shows that in vitro cellular stress on peripheral blood mononuclear cells and a pancreatic beta cell line leads to the release of soluble death receptors. The mechanism for death receptor release remains to be determined, but could

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

Background Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis. Objectives We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics. Methods NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386 days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively. Findings From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p = 0.012; p = 0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p = 0.027) and percentage of plaque occupied by necrotic core (p = 0.011), as well as lipid core burden index (p = 0.024) in the worst 4 mm segment. Interpretation Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.

FEMALE GENDER AND CORONARY INTERVENTION ARE SIGNIFICANT RISK FACTORS FOR CARDIAC CATHETERISATION-RELATED STROKE IN A TERTIARY CENTRE EXPERIENCE OVER A THREE YEAR PERIOD

Peri-procedural stroke is a serious complication of cardiac catheterisation, with varying incidence and uncertain management. This study determines the incidence and management of cardiac catheterisation-related stroke in a large single centre retrospective cohort. Data was acquired retrospectively

Trends in Mortality From Ischemic Heart Disease and Cerebrovascular Disease in EuropeClinical PERSPECTIVE

Background— Trends in cardiovascular mortality across Europe demonstrate significant geographical variation, and an understanding of these trends has a central role in global public health. Methods and Results— Ischemic heart disease and cerebrovascular disease age-standardized death rates (as per International Classification of Diseases, ninth and tenth revisions) were collated from the World Health Organization mortality database for member states of the European Union. Trends were characterized by using Joinpoint regression analysis. An overall trend for reduction in ischemic heart disease mortality was observed, most pronounced in Western Europe (>60% for the Netherlands, United Kingdom, and Ireland) for both sexes from 1980 to 2009. Eastern European states, Romania, Croatia, and Slovakia, had modest mortality reductions. Most recently (2009), Lithuania had the highest mortality for males and females (318.1/100 000 and 166.1/100 000, respectively), followed by Latvia and Slovakia. France had the lowest mortality: 39.8/100 000 for males and 14.7/100 000 for females. Analysis of cerebrovascular disease mortality revealed that Austria had the largest reduction for both sexes (76.8% males, 76.5% females) from 1980 to 2009. The smallest improvement over this period was seen in Lithuania, Poland, and Cyprus (–5% to +20% approximately). France has the lowest present-day cerebrovascular disease mortality for both males and females (23.9/100 000 and 17.3/100 000, respectively). Conclusions— There is a growing disparity in cardiovascular mortality between Western and Eastern Europe, for which diverse explanations are discussed. The need for population-wide health promotion and primary prevention policies is emphasized.

Trends in Mortality From Ischemic Heart Disease and Cerebrovascular Disease in EuropeClinical PERSPECTIVE: 1980 to 2009

Background— Trends in cardiovascular mortality across Europe demonstrate significant geographical variation, and an understanding of these trends has a central role in global public health. Methods and Results— Ischemic heart disease and cerebrovascular disease age-standardized death rates (as per International Classification of Diseases, ninth and tenth revisions) were collated from the World Health Organization mortality database for member states of the European Union. Trends were characterized by using Joinpoint regression analysis. An overall trend for reduction in ischemic heart disease mortality was observed, most pronounced in Western Europe (>60% for the Netherlands, United Kingdom, and Ireland) for both sexes from 1980 to 2009. Eastern European states, Romania, Croatia, and Slovakia, had modest mortality reductions. Most recently (2009), Lithuania had the highest mortality for males and females (318.1/100 000 and 166.1/100 000, respectively), followed by Latvia and Slovakia. France had the lowest mortality: 39.8/100 000 for males and 14.7/100 000 for females. Analysis of cerebrovascular disease mortality revealed that Austria had the largest reduction for both sexes (76.8% males, 76.5% females) from 1980 to 2009. The smallest improvement over this period was seen in Lithuania, Poland, and Cyprus (–5% to +20% approximately). France has the lowest present-day cerebrovascular disease mortality for both males and females (23.9/100 000 and 17.3/100 000, respectively). Conclusions— There is a growing disparity in cardiovascular mortality between Western and Eastern Europe, for which diverse explanations are discussed. The need for population-wide health promotion and primary prevention policies is emphasized.