Improvement In Cardiovascular Mortality Research Articles

Stalling life expectancy trends in Europe and decomposition analysis of mortality data

Abstract Background Life expectancy (LE) is an important population health metric over the life course. LE has increased significantly, over the past two centuries but has showed signs of slowing recently in Europe, the United Kingdom, and the United States. Several drivers have been suggested to be causing the slowdown, including slowing improvements in cardiovascular mortality. We set out to investigate trends in LE across Europe from 1990-2019, and how deaths from different causes have contributed to annual average change in LE across two time periods: 2007-2009 to 2012-2014 and 2012-2014 to 2017-2019. Methods Data were obtained from the Global Burden of Disease (GBD) Study 2019, which are in public domain. The GBD Study is a comprehensive global epidemiologic data resource employing standardized methodology for comparability. Joinpoint regression analysis was utilised to identify trends. The Arriaga decomposition method was applied to produce estimates of the contribution of different age groups and underlying causes of death to changes in LE at birth for the two periods. Results Overall, LE in Europe was 72.6 years in 1990- increasing to 78.3 years in 2019, with significant variations within EU countries. However, LE showed a slower pace from 2012 onwards in Europe- much slower in Western Europe, and more pronounced among females. LE in females fell from an annual increase of 0.38% between 2003-2012 to 0.16% between 2012-2019, and LE in males showed a similar pattern (from 0.66% between 2004-2012 to 0.26% between 2012-1019). Overall, improvements in mortality from almost all causes of death slowed, with LE contributions from improvements in ischemic heart disease (IHD) reduced by half. Conclusions LE is slowing down in Europe, especially in the Western region. Females and the elderly are facing the brunt of the slowdown. Slowing improvements in IHD mortality are the primary driver of the LE slowdown. Key messages • Life expectancy has overall improved in Europe but has slowed down from 2012 onwards- more pronounced among females and in Western Europe. • The decomposition analyses showed that improvements in mortality from all causes of death slowed, life expectancy contributions from improvements in ischemic heart disease (IHD) reduced by half.

Percutaneous Coronary Interventions in Women.

Cardiovascular disease is the leading cause of morbidity and mortality among women globally. Numerous studies show ongoing disparities in diagnosis, management, and outcomes of ischemic heart disease in women compared to men. We aim to review the factors contributing to sex-based differential outcomes of percutaneous coronary interventions in women. Hormonal influence on coronary arteries and progression of atherosclerosis in women results in distinct coronary plaque characteristics and unique pathological process such as spontaneous coronary artery dissection and myocardial infarction with non-obstructive coronary arteries. During the presentation of acute coronary syndromes, women are older and have higher burden of comorbidities, with higher short- and long-term mortality. Awareness of differences in vascular biology and unique risk factors for cardiovascular disease in women is essential for sustained improvement in cardiovascular mortality. Better representation of women in trials is crucial to address the gaps in knowledge and allow for individualized treatment approaches in women.

Sacubitrilo-valsartán: 5 años de experiencia clínica en pacientes ambulatorios con insuficiencia cardiaca

Introduction and objectivesSacubitril/valsartan (SV) has been shown to reduce cardiovascular mortality and readmissions in patients with heart failure and reduced ejection fraction (HFrEF). Our goal is to analyze in a real-life outpatient cohort of patients with HFrEF the effect of replacing angiotensin-converting-enzyme inhibitors with SV. MethodsRetrospective registry that included outpatients treated with SV in a third-level center. ResultsBetween 2016 and 2020, 419 patients with a median follow-up of 34 months were included; 16% (95%CI, 12.49-19.51) discontinued the drug. Mortality was 7.17 per 100 patients/year; 15% (95%CI, 11.58-18.42) had a heart failure hospitalization; 28.2% (95%CI, 23.89-32.51) improved ejection fraction, being a group with lower cardiovascular mortality and heart failure hospitalization (P<.001); 63.3% abandoned the previous indication of devices in primary prevention after initiation of SV. The predictors of improvement were the non-ischemic etiology (OR=0,35; 95%CI, 0.22-0.55; P<001) and the shortest evolution of the disease (OR=4.17; 95%CI, 2.35-7.38; P<.001). Patients with long-term HFrEF also showed improvement in left ventricular ejection fraction. ConclusionsReplacing angiotensin-converting-enzyme inhibitors with SV in patients with HFrEF had a significative impact in left ventricular ejection fraction, which implies an improvement in cardiovascular mortality and morbidity, a benefit that also exists in patients with a longer chronology of the disease. This improvement also associated a reduction in the indication of devices, especially in non-ischemic patients.

JIM Reading List.

JIM Reading List.

New Innovations in Treatment and Monitoring of Heart Failure With Guidelines on the Use of Sacubitril/Valsartan and Ivabradine

Background: Heart failure is a clinical syndrome that carries a significant burden of morbidity and is associated with poor long-term prognosis. Treatment of heart failure is constantly evolving, with large amounts of research going into the development of new medications, in the hopes of improving symptom management as well as reducing morbidity and mortality. Area of Uncertainty: One of the major areas of uncertainty regarding recent advances in heart failure management is the applicability of data from existing trials to the geriatric population. The majority of current research focuses on patients in a younger age group with a median age around 60, and there is a lack of randomized control trials assessing efficacy in the geriatric population specifically. Therapeutic Advances: Three new medications are examined in this review: sacubitril/valsartan, ivabradine, and nesiritide. Sacubitril/valsartan is a combination of neprilysin inhibitor and angiotensin receptor blocker that acts to increase natriuretic peptides and block the effect of angiotensin, leading to diuresis and vasodilation. The resultant reduction in systemic blood pressure and intravascular volume leads to decreased cardiac stress. This drug has Class 1B recommendation for the treatment of heart failure with reduced ejection fraction, with superior improvement in cardiovascular mortality and hospitalization rate compared with enalapril. Ivabradine is an If channel inhibitor that allows for selective reduction in heart rate without hindering cardiac contractility. This drug has Class IIa-B recommendation for heart failure with reduced ejection fraction with evidence of reduction in hospital admission rate. Nesiritide is a recombinant human brain natriuretic peptide that causes arterial and venous dilation and suppression of the renin–angiotensin–aldosterone system. Clinical trials have shown that this medication has some positive effect with patients in acute heart failure exacerbation; however, no benefit in long-term management has been shown. Conclusion: As the population of the United States continues to age, the number of patients with heart failure will continue to rise. Understanding the wide range of treatment options available to elderly patients is increasingly important for clinicians. Determining whether any of the new therapeutic options is appropriate for a patient will be a collaborative effort between a clinician and patient and will depend heavily on the patient's comorbidities, functional status, and goals of care.

Decreased Cardiovascular Mortality in Patients with Incident Rheumatoid Arthritis (RA) in Recent Years: Dawn of a New Era in Cardiovascular Disease in RA?

To assess trends in cardiovascular (CV) mortality in patients with incident rheumatoid arthritis (RA) in 2000-07 versus the previous decades, compared with non-RA subjects. The study population consisted of Olmsted County, Minnesota, USA residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria was met in 1980-2007) and non-RA subjects from the same underlying population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2014. Followup was truncated for comparability. Aalen-Johansen methods were used to estimate CV mortality rates, adjusting for competing risk of other causes. Cox proportional hazards models were used to compare CV mortality by decade. The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 yrs; 68% women for both groups). Patients with incident RA in 2000-07 had markedly lower 10-year overall CV mortality (2.7%, 95% CI 0.6-4.9%) and coronary heart disease (CHD) mortality (1.1%, 95% CI 0.0-2.7%) than patients diagnosed in 1990-99 (7.1%, 95% CI 3.9-10.1% and 4.5%, 95% CI 1.9-7.1%, respectively; HR for overall CV death: 0.43, 95% CI 0.19-0.94; CHD death: HR 0.21, 95% CI 0.05-0.95). This improvement in CV mortality persisted after accounting for CV risk factors. Ten-year overall CV mortality and CHD mortality in 2000-07 RA incidence cohort was similar to non-RA subjects (p = 0.95 and p = 0.79, respectively). Our findings suggest significantly improved overall CV mortality, particularly CHD mortality, in patients with RA in recent years. Further studies are needed to examine the reasons for this improvement.

Association between perceived lifetime risk of cardiovascular disease and calculated risk in a male population in Brazil.

AimCardiovascular disease is the major cause of morbidity and mortality across the world. Despite health campaigns to improve awareness of cardiovascular risk factors, there has been little improvement in cardiovascular mortality. In this study, we sought to examine the association between cardiovascular risk factors and people’s perception on cardiovascular risk.MethodsThis was an epidemiological, cross-sectional, descriptive, prospective study of Masonic men aged >40 years in Boa Vista, Brazil. Participants completed a health survey, which included three questions about perception of their stress level, overall health status, and risk of a heart attack. In addition, demographic and biological data were collected.ResultsA total of 101 Masonic men took part in the study; their mean age (± standard deviation) was 55.35±9.17 years and mean body mass index was 28.77±4.51 kg/m2. Answers to the lifestyle questionnaire suggested an overall healthy lifestyle, including good diet and moderate exercise, although despite this ~80% were classified as overweight or obese. The majority of participants felt that they had a low stress level (66.3%), good overall general health (63.4%), and were at low risk of having a heart attack (71.3%). Masons who were overweight were significantly more likely to perceive themselves to be at risk of a heart attack (P=0.025).ConclusionDespite over half of participants having a moderate to high risk of cardiovascular disease according to traditional risk factors, less than a third perceived themselves to be at high risk. Public health campaigns need to better communicate the significance of traditional cardiovascular risk in order to improve awareness of risk among the general population.

Incidence and trends of cardiovascular mortality after common cancers in young adults: Analysis of surveillance, epidemiology and end-results program.

To describe the incidence of cardiovascular mortality (CVM) in survivors of major cancers and identify its trends over the past two decades. We used the surveillance, epidemiology and end-results 19 registry to identify young adults (20-49 years), diagnosed with the following major primary cancers: Lung, breast, liver/intrahepatic bile duct, pancreas, prostate, colorectal, and ovarian from 1990 through 2012 and identified the cumulative incidence of CVM after adjusting for confounding factors. We identified a total of 301923 cancers (breast 173748, lung 38938, colorectal 31722, prostate 22848, ovary 16065, liver 9444, pancreas 9158). A total of 2297 (0.8%) of patients had incident CVM. Lung (10-year cumulative CVM 2.4%) and liver (1.73%) cancers had the highest incidence of CVM, while breast (0.6%) and prostate (1.2%) had the lowest CVM mortality, even after multiple adjustments (P < 0.001). Overall, there was a significant improvement in CVM since 1990 [2005-2012 vs 1990-1994, adjusted HR 0.63 (0.54-0.72), P < 0.001]. This was driven by improvements in CVM in lung cancers (P = 0.02), breast (P < 0.001), and a trend in ovarian cancer (P = 0.097). There was no statistically significant improvement in CVM among survivors of colorectal, pancreatic, liver, or prostate cancers. The risk of CVM differs among different cancers, and is highest among survivors of lung and liver cancers. The incidence of CVM has decreased over the past 2 decades mainly among survivors of lung and breast cancers.

Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs.

Since their introduction, statin (HMG-CoA reductase inhibitor) drugs have advanced the practice of cardiology to unparalleled levels. Even so, coronary heart disease (CHD) still remains the leading cause of death in developed countries, and is predicted to soon dominate the causes of global mortality and disability as well. The currently available non-statin drugs have had limited success in reversing the burden of heart disease, but new information suggests they have roles in sizeable subpopulations of those affected. In this review, the status of approved non-statin drugs and the significant potential of newer drugs are discussed. Several different ways to raise plasma high-density lipoprotein (HDL) cholesterol (HDL-C) levels have been proposed, but disappointments are now in large part attributed to a preoccupation with HDL quantity, rather than quality, which is more important in cardiovascular (CV) protection. Niacin, an old drug with many antiatherogenic properties, was re-evaluated in two imperfect randomized controlled trials (RCTs), and failed to demonstrate clear effectiveness or safety. Fibrates, also with an attractive antiatherosclerotic profile and classically used for hypertriglyceridemia, lacks evidence-based proof of efficacy, save for a subgroup of diabetic patients with atherogenic dyslipidemia. Omega-3 fatty acids fall into this category as well, even with an impressive epidemiological evidence base. Omega-3 research has been plagued with methodological difficulties yielding tepid, uncertain, and conflicting results; well-designed studies over longer periods of time are needed. Addition of ezetimibe to statin therapy has now been shown to decrease levels of low-density lipoprotein (LDL) cholesterol (LDL-C), accompanied by a modest decrease in the number of CV events, though without any improvement in CV mortality. Importantly, the latest data provide crucial evidence that LDL lowering is central to the management of CV disease. Of drugs that inhibit cholesteryl ester transfer protein (CETP) tested thus far, two have failed and two remain under investigation and may yet prove to be valuable therapeutic agents. Monoclonal antibodies to proprotein convertase subtilisin/kexin type 9, now in phase III trials, lower LDL-C by over 50% and are most promising. These drugs offer new ability to lower LDL-C in patients in whom statin drug use is, for one reason or another, limited or insufficient. Mipomersen and lomitapide have been approved for use in patients with familial hypercholesterolemia, a more common disease than appreciated. Anti-inflammatory drugs are finally receiving due attention in trials to elucidate potential clinical usefulness. All told, even though statins remain the standard of care, non-statin drugs are poised to assume a new, vital role in managing dyslipidemia.

Hypoglycemia and cardiovascular risk

Intensive glycemic control and aggressive glycated hemoglobin targets <7.0% have failed to show an improvement in cardiovascular mortality. Repetitive and severe hypoglycemic episodes with intensive glucose-lowering therapy may be a major factor in the failure to show cardiovascular benefit in diabetic patients. In this article, the cardiovascular effects of hypoglycemia, and the trials with an intensive glucose-lowering strategy that have studied microvascular and macrovascular complications are discussed. The current non-insulin drugs, which do not induce hypoglycemia, available for the treatment of diabetes and their cardiovascular impacts are clarified.

SEX AND GENDER IN HEART DISEASE PREVENTION: CONSIDERING THE IMPACT OF POLYCYSTIC OVARY SYNDROME

Despite overall improvements in cardiovascular mortality, young women who experience ischemic heart disease (IHD) continue to have high mortality rates. Furthermore, young women often do not benefit from IHD primary prevention initiatives because they are younger than the age at which risk factor screening typically commences. Unique to women may be a predisposition to early onset of IHD because of endocrine and metabolic conditions such as polycystic ovary syndrome (PCOS). PCOS typically consists of menstrual irregularities, subfertility, and hyperandrogenism and affects 7-18% of women of reproductive age.

FRI0117 Analysis of risk for cardiovascular events and assessment of diagnostic and therapeutic management of patients with rheumatoid arthritis in clinical practice: the epidauro registry.

BackgroundA number of studies have clearly documented a higher mortality rate in patients with rheumatoid arthritis (RA) than in general population, comparable to that found in patients with type 2...

Vasopressin V1 receptor‐mediated aldosterone production as a result of selective V2 receptor antagonism: a potential explanation for the failure of tolvaptan to reduce cardiovascular outcomes in the EVEREST trial

Plasma volume expansion in patients with heart failure (HF) is associated with neurohumeral activation; symptom and signs of pulmonary congestion and peripheral oedema; an increase in hospitalizations for HF; and cardiovascular mortality. A reduction in plasma volume, as evidenced by haemoconcentration, has recently been suggested to be associated with an improvement in cardiovascular mortality. However, while loop diuretics reduce plasma volume and relieve the symptoms and signs of pulmonary congestion, they activate the renin–angiotensin–aldosterone system (RAAS) and, in experimental studies and some, although not all, retrospective clinical studies have been associated with an increase in cardiovascular mortality. Due to the controversy associated with the use of high-dose loop diuretics and their effect on cardiovascular mortality in patients with HF and a reduced left ventricular ejection fraction (REF) there has been increasing interest in alternative and or supplemental diuretic strategies to reduce plasma volume and to improve cardiovascular outcomes in patients with HFREF. Tolvaptan, a selective V2 vasopressin antagonist, has been shown in pre-clinical and short-term studies in patients with HF to be a potent aquaretic with a resultant increase in urine output; a decrease in body weight; a decrease in pulmonary capillary wedge pressure; an increase in serum sodium concentration; without activation of the RAAS. However when studied over the longer term in patients with HFREF, it has not been shown to reduce natriuretic peptide levels or left ventricular remodelling, and did not improve cardiovascular outcomes despite an early improvement in symptoms of dyspnoea, a prolonged reduction in body weight, and normalization of serum sodium in hyponatraemic patients. The finding that tolvaptan failed to reduce natriuretic peptide levels and cardiovascular outcomes despite a reduction in body weight is especially notable since an increase in body weight post-discharge is the single most important predictor for readmission in patients with heart failure and a major predictor of mortality. The explanation for the failure of tolvaptan to improve ventricular remodelling, natriuretic peptide levels, and cardiovascular outcomes despite a reduction in body weight remains uncertain. Several explanations have, however, been proposed, including the suggestion that the dose of tolvaptan (30 mg/day) may have been inadequate; that patients selected for study did not have hyponatraemia; and the possibility that a reactive increase in vasopressin levels might over the long term stimulate the V1a receptor with a resultant increase in vasoconstriction, which might negate the beneficial effects associated with aquareses. Without further prospective mechanistic studies it is difficult to confirm or refute these explanations. Recently, however, it has been shown that a deficiency of the V1a receptor causes hyporeninaemic hypoaldsteronism, and stimulation of the V1a receptor causes the adrenal production of aldosterone. The V1a receptor also affects the renal tubular effects of aldosterone. We postulate that these findings may explain the paradox of a persistent reduction in body weight despite the lack of an improvement in natriuretic peptide levels and cardiovascular outcomes associated with the use of tolvaptan in EVEREST. This hypotheses and its implications for the therapy of patients with HF will be briefly discussed below. As noted above, V2 receptor antagonism results in a sustained reduction in body weight along with an early transient decrease in pulmonary capillary wedge pressure without activation of the RAAS. However, over the long term there is a reactive increase in vasopressin levels, with a resultant increased activation of the unprotected V1a receptor in the myocardium and vascular wall. This increase in vasopressin levels in patients receiving tolvaptan has recently been associated with an increase in aldosterone levels.

Home hemodialysis: Present state of the evidence

disappointing results suggested that the high mortality associated with hemodialysis could not be impacted upon with relatively small increases in solute clearance. It also further questioned the rationale of focusing on Kt/V as a measure of dialysis adequacy. The mortality rate for hemodialysis patients in the U.S. is high at approximately 24.4 deaths/100 patient-years.4 The high mortality rate has persisted despite progressive increases in Kt/V over the past two decades, from 1.11 in 1991 to 1.52 in 2002.5 In addition, despite this increase in Kt/V, the complications of hypertension,6 malnutrition,7 congestive heart failure,8 and bone and mineral disorders9 have remained unacceptably high. These outcome data clearly indicate that dialysis adequacy cannot be simply measured in terms of Kt/V. Given these persistently poor outcomes

The diagnosis and treatment of growth hormone deficiency in adults

This review summarizes the recent published information regarding efficacy and complications of growth hormone replacement therapy. Several recent reports have monitored patients for periods of up to 10 years. Additionally, a consensus conference has been held regarding needed improvements in diagnostic testing and the recommendations of consensus panels regarding diagnostic criteria and laboratory test utilization are summarized. Long-term studies show growth hormone can be administered safely and that muscle strength and function as well as lipoprotein abnormalities and low-bone mineral density show sustained improvement over extended periods of time. The complications that occur are generally dose-dependent and once attenuated do not tend to recur. Long-term safety studies regarding improvement in cardiovascular mortality and/or worsening prognosis for patients who develop malignancies are available only in the form of observational studies and randomized controlled long-term trial information is not yet available. The studies reported provide a means for clinicians to ascertain the patients who are likely to derive the greatest benefit from growth hormone when the appropriate diagnostic testing and treatment paradigms are utilized. The studies that are summarized provide useful information for assessing the response to treatment, selecting patients who are candidates for long-term replacement therapy and for selecting those in whom the need for therapy may need to be reassessed.

A Cardiologist’s View of Hypoglycemia

Recent studies have failed to show an improvement in cardiovascular mortality with intensive glycemic control and aggressive glycated hemoglobin (A(1c)) targets less than 7.0%. Excessive hypoglycemic episodes with intensive glucose-lowering therapy are thought to be a major factor in the failure to show cardiovascular benefit in these trials. In this article, we review the physiology of glucose metabolism, the cardiovascular pathophysiology of hypoglycemia, and the trials with an intensive glucose-lowering strategy that have studied microvascular and macrovascular complications. We also review the current non-insulin drugs available for the treatment of diabetes and their potential hypoglycemic and cardiovascular impacts.

Beyond Established and Novel Risk Factors

Dyslipidemia, hypertension, and diabetes mellitus have been appropriately highlighted as established predictors of cardiovascular disease. These risk factors have become preeminent targets for influencing cardiovascular risk; their assessment, treatment, and monitoring are major emphases of clinical care, research investigation, treatment guidelines, organization position papers, and measures of physician and hospital performance. Notably, lifestyle risk factors, including dietary habits, physical inactivity, smoking, and adiposity, strongly influence the established cardiovascular risk factors and also affect novel pathways of risk such as inflammation/oxidative stress, endothelial function, thrombosis/coagulation, and arrhythmia. Furthermore, modest alterations of these lifestyle risk factors are achievable and have substantial effects on cardiovascular risk. Thus, basic lifestyle habits should be considered fundamental risk factors for cardiovascular disease. Although efforts to combat established and novel risk factors with pharmacological treatments are important and should continue, we call for a systematic rebalancing of current research, clinical care, and policy efforts to focus more on lifestyle. The rising costs of healthcare and the epidemics of overweight and obesity highlight the inadequacies of our current strategy. Substantially more resources should be directed toward research on lifestyle risk factors, their determinants, and effective interventions to change them. The clinical evaluation and treatment of dietary, physical activity, and smoking habits must become as routine and familiar as assessment of blood pressure, cholesterol, and glucose levels. Major policy initiatives and reimbursement guidelines must also be rebalanced to emphasize lifestyle risk factors. Cardiovascular diseases are leading causes of death and disability among men and women in nearly all nations.1 Identification of persons at higher or lower risk for cardiovascular events is important to facilitate effective use of resources and interventions to reduce disease burden among individuals and in society. Each of the established risk factors for cardiovascular disease—age, gender, dyslipidemia, hypertension, diabetes mellitus, and smoking—have been appropriately highlighted …

Cardiovascular and Tuberculosis Mortality: The Contrasting Effects of Changes in Two Causes of Death

Tuberculosis was the largest source of deaths among younger adults, and cardiovascular disease among older adults, in the America of 1900. Decreases in deaths from tuberculosis since 1900 and cardiovascular disease since 1940 explain most of the mortality drops in those age groups over the century. This article, building on previous work by White and Preston, shows the results of increased survival from these two causes on the US population structure. Standard demographic cause-specific mortality calculations are used to generate life tables without deaths from cardiovascular disease or tuberculosis. Then fixed rates for these diseases from early in the century are assumed while all other causes of death are allowed to change as they did historically. Improvements in cardiovascular mortality and tuberculosis produce some seemingly illogical contrasts. More people are alive today because of the decrease in tuberculosis. Yet more deaths from cardiovascular disease have been prevented, and cardiovascular improvements have raised life expectancy more. Lower tuberculosis mortality had virtually no effect on the average age of the population. Lower cardiovascular mortality alone has raised that average more than all twentieth-century causes of improved mortality combined.

Trends in mortality from cerebrovascular diseases in the United States, 1960 to 1975.

A long-term decline in death rates from cerebrovascular diseases in the United States accelerated in 1969, with a further increase in the rate of decline after 1972. This break in the pattern of the mortality curve for stroke was observed in all 4 major sex-color groups, and affected all age groups in which a significant number of stroke deaths occur. The decline for non-whites was relatively and absolutely greater than for the comparable white sex. If the 1960 rates had persisted in 1975, 87,600 more lives would have been lost to cerebrovascular diseases. Although there are no data documenting a declining prevalence of hypertension in the population, detection, treatment and control of hypertension have improved markedly over recent years. A concomitant decrease in the severity of epidemic respiratory infection may have contributed to the improvement in recorded death rates from stroke. Mortality from all major cardiovascular diseases has demonstrated a parallel downward trend. Continued emphasis on public health efforts to detect and treat hypertension and other known cardiovascular risk factors can be expected to result in further improvement in cardiovascular mortality.