Allegra Battistoni

Cardiovascular risk assessment beyond Systemic Coronary Risk Estimation: A role for organ damage markers

Background: Cardiovascular risk assessment in the clinical practice is mostly based on risk charts, such as Framingham risk score and Systemic Coronary Risk Estimation (SCORE). These enable clinicians to estimate the impact of cardiovascular risk factors and assess individual cardiovascular risk profile. Risk charts, however, do not take into account subclinical organ damage, which exerts independent influence on risk and may amplify the estimated risk profile. Inclusion of organ damage markers in the assessment may thus contribute to improve this process. Objective: Our aim was to evaluate the influence of implementation of SCORE charts with widely available indexes of organ damage, with the purpose to ameliorate individual risk assessment. Methodology: We searched www.Pubmed.gov for evidence about the predictive value of left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU) and metabolic syndrome on different risk profiles estimated by SCORE. Interventional and observational trials including at least 200 patients and published after 2000 were selected. Results: The presence of organ damage as well as the number of abnormal parameters indicating organ damage is associated with increased cardiovascular risk, independently of SCORE. In the area of high risk, the impact of different markers of organ damage is heterogeneous. Combined risk models of SCORE and subclinical organ damage have major impact on risk stratification and may impact on recommendation in primary prevention in all SCORE categories. Conclusion: Available evidence suggests a tangible clinical advantage of adding the evaluation of simple organ damage markers to risk charts in cardiovascular risk prediction.

Circulating biomarkers with preventive, diagnostic and prognostic implications in cardiovascular diseases

The search for molecules that may contribute to better identify patients at risk for cardiovascular diseases (CVD) represents today an active field in clinical research. Few biomarkers have already been identified as reliable and useful tools in medical decision making, such as cardiac troponin (cTn) and NT-proBNP. At the same time, evidence regarding the possible role of other molecules is piling up. Every new putative biomarker has demonstrated effectiveness in at least one clinical application: cardiovascular risk assessment, diagnosis or outcome prediction. On the other hand, combination of preventive, diagnostic and prognostic implications for the same molecule is expected to improve enormously the usefulness of a biomarker in medicine. We performed a search of the literature looking for circulating molecules found to exert discriminating abilities in all three mentioned clinical applications. The purpose of the present review is to bring to the attention of medical and research communities those biomarkers for which a relevant amount of evidence has been accumulated regarding their potential application in all clinical steps of the cardiovascular continuum. Furthermore, since simultaneous testing of different plasmatic molecules has been proposed as a suitable tool to improve medical decision making, we also discuss feasible associations of biomarkers that promise to be the most effective for cardiovascular risk assessment in the general population and for outcome prediction in patients affected by acute coronary syndrome (ACS) and by heart failure (HF).

NPR-C: a component of the natriuretic peptide family with implications in human diseases

The natriuretic peptide (NP) family includes atrial natriuretic peptide (ANP), B-type natriuretic peptide, C-type natriuretic peptide and their receptors NPR-A, NPR-B and NPR-C. The effects exerted by this hormonal system in the control of cardiovascular, renal and endocrine functions have been extensively investigated. Moreover, the involvement of NP in the pathogenesis of cardiovascular diseases has been demonstrated. Among the NP components, NPR-C has been described, at the time of its discovery, as the clearance receptor of NP devoid of any physiological functions. Emerging roles of NPR-C, however, have been highlighted over the last few years in relation to its effects on the cardiovascular system and other organs. These effects appear to be directly mediated through distinct cAMP-dependent intracellular mechanisms. Moreover, evidence has been accumulated on a potential pathophysiological role of NPR-C in human diseases. Ongoing studies from our group are revealing its involvement in the mediation of antiproliferative effects exerted on vascular cells by a molecular variant of human ANP. Thus, a new appraisal of NPR-C is overcoming the traditional view of a mere clearance receptor. This review focuses on the most important evidence supporting an involvement of NPR-C in mediating some of the actions of NP and its direct implication in cardiovascular diseases. The current state of knowledge highlights the need of further studies to better clarify the specific roles of NPR-C in pathophysiological processes.

Non-invasive diagnostic testing for coronary artery disease in the hypertensive patient: potential advantages of a risk estimation-based algorithm.

Hypertension is a major risk factor for cardiovascular disease, including coronary atherosclerosis and its clinical manifestations. Non-invasive diagnosis of coronary artery disease in hypertension, however, remains a major clinical challenge. Chest pain frequently occurs in hypertensive patients with and without impairment of coronary blood flow supply. Electrocardiographic abnormalities are also common in these patients, thereby leading to further diagnostic difficulty. On the other hand, international guidelines are rather elusive on the recommended diagnostic pathway for coronary artery disease detection in hypertensive patients.In this article, we review the strengths and limitations of current diagnostic methods used to properly identifying coronary artery disease in hypertensive patients. Furthermore, we analyze the usefulness of adopting preliminary and comprehensive cardiovascular risk stratification, together with the evaluation of markers of organ damage, in order to improve the diagnostic efficacy.Despite the high prevalence of arterial hypertension, we still lack a strategy which would lead to validated and cost-effective clinical decision-making processes in hypertensive patients, which help clinicians to minimize useless, ineffective and expensive diagnostic steps. For this purpose, future guidelines should address the issue of diagnostic strategies for an early identification of hypertensive patients at risk of coronary artery disease. This may facilitate appropriate therapeutic choices to optimize the clinical management of coronary disease in hypertension.

Renin as a biomarker of cardiovascular disease in clinical practice

The search for novel circulating blood biomarkers as predictors of cardiovascular (CV) risk and prognosis is a continuing field of interest in clinical medicine. Biomarkers from several pathophysiological pathways, including markers of organ damage, of inflammation, of the atherosclerotic process and of the coagulation pathway, have been investigated in the last decades. A particular interest has been raised for neurohormonal factors. The role of the activation of the sympathetic system and the renin-angiotensin-aldosterone system (RAAS) in the development of CV diseases has been extensively explored. Renin is the first limiting step of the RAAS and its role as a biomarker to improve CV risk stratification still remains a topic of debate. Several studies have shown that elevated plasma renin activity is associated with increased morbidity and mortality in patients with CV disease. The aim of this paper is to critically evaluate the evidence on the role of renin as a biomarker of CV risk and prognosis. With the new advances of pharmacological treatment acting on the RAAS, the effect of elevated levels of renin on the prognosis of these patients becomes even more intriguing.

Reducing Cardiovascular and Cancer Risk: How to Address Global Primary Prevention in Clinical Practice

Emerging evidence suggesting the possibility that interventions able to prevent cardiovascular disease (CVD) may also be effective in the prevention of cancer have recently stimulated great interest in the medical community. In particular, data from both experimental and observational studies have demonstrated that aspirin may play a role in preventing different types of cancer. Although the use of aspirin in the secondary prevention of CVD is well established, aspirin in primary prevention is not systematically recommended because the absolute cardiovascular event reduction is similar to the absolute excess in major bleedings. By adding to its cardiovascular prevention benefits, the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in primary prevention in favor of the latter and broaden the indication for treatment with aspirin in populations at average risk. Prospective and randomized studies are currently investigating the effect of aspirin in prevention of both cancer and CVD; however, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention already could be made on the basis of a balanced evaluation of the benefit/risk ratio.

Calcium channel blockers and hypertension.

Effective treatment of high blood pressure (BP) represents a key strategy for reducing the burden of hypertension-related cardiovascular and renal diseases. In spite of these well-established concepts, hypertension remains poorly controlled worldwide. In order to improve BP control in patients with hypertension, several interventions have been proposed, among which (1) preferred use of more effective, sustained, and well-tolerated antihypertensive drug aimed to ensure adherence to prescribed medications and (2) extensive use of rational, integrated, and synergistic combination therapies, even as first-line strategy, aimed to achieve the recommended BP targets. Within the possible antihypertensive drug classes currently available for the clinical management of hypertension, both in monotherapy and in combination therapy, drugs inhibiting the renin–angiotensin system and calcium channel blockers (CCBs) have demonstrated to be effective and safe in lowering BP levels and achieving the recommended BP targets with a good tolerability profile. In particular, CCBs have been one of the most widely used classes of antihypertensive agents in the last 20 years, based on their effectiveness in reducing BP levels, good tolerability, and abundant evidence on reducing cardiovascular and renal consequences of hypertension. This article provides an updated overview of the evidence supporting the use of CCBs-based antihypertensive regimen, both in monotherapy and in combination therapies with different classes of antihypertensive drugs.

Hypertension in Young People: Epidemiology, Diagnostic Assessment and Therapeutic Approach

AbstractHigh blood pressure (BP) still remains one of the most relevant cardiovascular risk factors, also due to its persistently high prevalence and growing incidence in the general adult and elderly population. Since almost all hypertension-related cardiovascular complications, mostly including coronary artery disease, myocardial infarction, ischemic stroke, and congestive heart failure, occurred in adult and elderly individuals, evidence on both prevalence and clinical management of hypertension in young individuals are lacking. Therefore, the clinical impact of high BP levels in young populations remains to be explored. In the recent years, the attitude of the scientific community has changed and more attention was devoted to young individuals with hypertension, also in view of the fact that early identification of these subjects may prevent developing of established hypertension in adulthood. In addition, unhealthy lifestyle habits have progressively involved children and adolescents worldwide, thus contributing to further increase the risk of developing hypertension in young individuals. On the basis of these considerations, the present review is aimed at providing a brief reappraisal of the major aspects of hypertension in the young age, as well as at promoting interest and discussion on this important issue.

Aminoterminal natriuretic peptides and cardiovascular risk in an Italian male adult cohort

adult cohort☆,☆☆ Antonio Barbato , Sebastiano Sciarretta , Simona Marchitti , Roberto Iacone , Sara Di Castro , Rosita Stanzione , Maria Cotugno , Renato Ippolito , Luigi Palmieri , Camilla Calvieri , Allegra Battistoni , Massimo Volpe , Pasquale Strazzullo , Speranza Rubattu b,c,⁎ and On behalf of the Olivetti Heart Study Research Group a Department of Clinical and Experimental Medicine, Federico II University of Naples Medical School, Naples, Italy b IRCCS Neuromed, Pozzilli (Is) Italy c Department of Cardiology, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome, Italy d Department of Cerebro and Cardiovascular Diseases Epidemiology, Istituto Superiore di Sanita, Rome, Italy

T2238C ANP gene variant and risk of recurrent acute coronary syndromes in an Italian cohort of ischemic heart disease patients

Background The role of C2238/atrial natriuretic peptide (ANP) minor allele, at the T2238C ANP gene variant, as a predisposing risk factor for acute cardiovascular events, has been previously reported. We aimed at evaluating, by a retrospective approach, the long-term impact of C2238/ANP-minor allele carrier status toward the risk of recurrent acute coronary syndromes (re-ACS) in an Italian cohort of ischemic heart disease patients. Methods A total of 379 patients (males = 80.5%; mean age = 62.5 ± 9.2 years) presenting with ACS were retrospectively analyzed. Mean follow-up was 5.1 ± 3.5 years (range 1–26 years). Occurrence of new episodes of unstable angina, non-ST-segment elevation myocardial infarction and STE myocardial infarction over the years was recorded and compared between subjects not carrying and carrying C2238/ANP-minor allele. Results At univariate analysis, C2238/ANP-minor allele carrier status and treatment with beta-blocker, aspirin and statin were associated with risk of re-ACS. Multivariate analysis confirmed that hypercholesterolemia (P < 0.0001) and C2238/ANP-minor allele carrier status (P < 0.05) were both significantly and independently associated with increased risk of re-ACS. Both treatments with beta-blocker and with statin were significantly associated with reduced risk of re-ACS (P = 0.01 and P < 0.01, respectively). Age above 55 years was associated with recurrence of ACS in C2238/ANP-minor allele carriers (hazard ratio 1.427, 95% confidence interval 1.066–1.911, P = 0.017). Kaplan–Meier curves confirmed highest risk of new events occurrence in C2238/ANP-minor allele carriers (P = 0.035). Conclusions The present results demonstrate that C2238/ANP-minor allele carrier status is an independent risk factor for ACS recurrence in an Italian cohort of ischemic heart disease patients over the long term, and they support the role of C2238/ANP-minor allele as a negative prognostic factor in coronary artery disease patients.