Secondary Risk Stratification Research Articles

Rationale and Design of the ACS-BP Study: Prognostic Value of In-Hospital Blood Pressure and Indices of Atherosclerosis in Acute Coronary Syndromes.

High blood pressure (BP) is a leading risk factor for coronary artery disease and other major cardiovascular events. Blood pressure variability (BPV), ambulatory arterial stiffness index (AASI) and ankle- brachial index (ABI) have been proposed as indices that can improve risk stratification for an adverse cardiac outcome. However, their utility in the setting of acute coronary syndromes (ACS) is unclear. The ACS-BP study is a single-centre observational cohort study designed to investigate the prognostic role of haemodynamic load and arterial stiffness indices for cardio-renal outcomes in patients with acute myocardial infarction (AMI). All consecutive patients admitted with a diagnosis of acute AMI with or without ST segment elevation were screened for inclusion in the study. The management of AMI will follow current guidelines. Data from baseline clinical and laboratory parameters during their hospitalization were collected. The haemodynamic load of each patient was determined by clinical BP values as well as 24-h ambulatory BP monitoring. The AASI was calculated from the raw 24-h BP data and ABI was measured after the third day of hospitalization using a certified device. Patients were followed-up for 12 months in order to collect data for hard cardiovascular and renal endpoints. The study results should clarify the role of these non-invasive tools in secondary risk stratification of such patients.

Routine Measurements of Cardiac Parasympathetic and Sympathetic Nervous Systems assists in Primary and Secondary Risk Stratification and Management of Cardiovascular Clinic Patients

Objective: To review our studies of the ease and importance of parasympathetic and sympathetic (P&S) measures in managing cardiovascular patients. Background: The autonomic nervous system is responsible for the development or progression of hypertension (HTN), orthostasis, coronary disease (CAD), heart failure (CHF), and arrhythmias. Finally, new technology provides us with rapid, accurate P and S measures critically needed to manage these patients much more successfully. Methods: Using the ANX 3.0 autonomic monitor, P&S activity was recorded in 4 studies: 163 heart failure patients in total, mean follow-up (f/u) 12-24.5 months; 109 orthostasis patients, f/u 2.28 years (yr), and 483 patients with risk factors or known HTN, CAD, or CHF, f/u 4.92 yrs. All were on guideline-driven therapy. Results: Fifty-nine percent (59%) of CHF patients had dangerously high sympathovagal balance(SB) or cardiac autonomic neuropathy (CAN), and Ranolazine markedly improved 90% of these, improved left ventricular ejection fraction in 70% of patients on average 11.3 units, and reduced MACE (acute coronary syndromes, death, acute CHF, ventricular tachycardia/fibrillation[VT/VF]) 40%. Sixty-six-percent (66%) of orthostatic patients corrected with (r) alpha lipoic acid ([r]ALA); non-responders had the lowest S-tone. In the 483 patient study, SB>2.5 best predicted MACE when compared to nuclear stress and echocardiography (sensitivity 0.59, OR 7.03 [CI 4.59-10.78], specificity 0.83, positive predictive value 0.64, and negative predictive value 0.80).

Routine Measurements of Cardiac Parasympathetic and Sympathetic Nervous Systems Assists in Primary and Secondary Risk Stratification and Management of Cardiovascular Clinic Patients

Objective: To review our studies of the ease and importance of Parasympathetic and Sympathetic (P&S) measures in managing cardiovascular patients. Background: The autonomic nervous system is responsible for the development or progression of Hypertension (HTN), orthostasis, Coronary Disease (CAD), Congestive Heart Failure (CHF) and arrhythmias. Finally, new technology provides us with rapid, accurate P and S measures critically needed to manage these patients much more successfully. Methods: Using the ANX 3.0 autonomic monitor, P&S activity was recorded in 4 studies: 163 heart failure patients in total, mean follow-up (f/u) 12-24.5 months; 109 orthostasis patients, f/u 2.28 years and 483 patients with risk factors or known HTN, CAD or CHF, f/u 4.92 yrs. All were on guideline-driven therapy. Results: 59% of CHF patients had dangerously high Sympathovagal Balance (SB) or Cardiac Autonomic Neuropathy (CAN) and Ranolazine markedly improved 90% of these, improved left ventricular ejection fraction in 70% of patients on average 11.3 units, and reduced Major Adverse Cardiac Event (MACE) [Acute Coronary Syndromes (ACS), death, acute CHF, Ventricular Tachycardia/Ventricular Fibrillation (VT/VF)] 40%. 66% of orthostatic patients corrected with (r) Alpha Lipoic Acid ([r]ALA); non-responders had the lowest S-tone. In the 483 patient study, SB>2.5 best predicted MACE when compared to nuclear stress and echocardiography (sensitivity 0.59 or 7.03 [CI (Confidence Interval) 4.59-10.78], specificity 0.83, positive predictive value 0.64 and negative predictive value 0.80). Conclusion: Parasympathetic and sympathetic measures significantly improve care of cardiovascular patients.

B-type natriuretic peptide molecular forms for risk stratification and prediction of outcome after acute myocardial infarction

BackgroundB-type natriuretic peptide (BNP) is known to be a risk marker following acute myocardial infarction (MI). More recently, truncated molecular forms of the BNP molecule have been identified, with the association of these forms and outcome in acute MI not known. The present study investigated their use as risk stratifying biomarkers of this condition. MethodsBNP molecular forms (BNP 5–32, BNP 4–32 and BNP 3–32) were measured in plasma from 1078 acute MI patients using immunocapture followed by MALDI-ToF-mass spectrometry. Associations of molecular forms with short-term and long-term adverse outcomes were assessed. ResultsBNP molecular forms were independent predictors of mortality/reinfarction, mortality/rehospitalization due to heart failure, and a composite of all events at 6 months, 1 year and 2 years and showed prognostic ability comparable with conventional BNP measurements (P<.001–0.026 vs. N-terminal [NT]-proBNP P<.001–0.020, respectively). Reclassification analyses showed BNP molecular forms successfully reclassified patient risk when used in addition to the GRACE clinical risk score (P≤.005). BNP 5–32 showed utility as a secondary risk stratification biomarker when used in combination with the GRACE score and NT-proBNP by successful down-classification of high-risk patients. ConclusionsBNP molecular forms were associated with poor prognosis at 6 months, 1 year and at 2 years in patients with acute MI. BNP 5–32 showed successful utility as a secondary marker in combination with NT-proBNP after GRACE scoring. This study suggests a potential role for BNP molecular forms in prognosis and risk stratification after acute MI.

Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction.

Risk stratification in acute myocardial infarction (MI) remains a clinical challenge. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, was investigated for its ability to assist in risk stratification for acute MI hospitalizations. TMAO was analyzed in 1079 acute MI patients. Associations with adverse outcome of all-cause mortality or reinfarction (death/MI) for shorter (6-month) and longer (2-year) terms were assessed and compared to other cohort-specific biomarkers. Added value in risk stratification by combined use with the Global Registry of Acute Coronary Events (GRACE) score was also investigated. TMAO independently predicted death/MI at 2 years [292 events, hazard ratio 1.21 (95% CI, 1.03-1.43), P = 0.023], but was not able to predict death/MI at 6 months (161 events, P = 0.119). For death/MI at 2 years, TMAO retained independent prediction of risk (P = 0.034) and improved stratification even after addition of multiple alternative and contemporary biomarkers previously shown to provide added prognostic value in this cohort. From these contemporary biomarkers, TMAO remained the only significant predictor of outcome. Further, TMAO improved risk stratification for death/MI at 6 months by down-classifying risk in patients with GRACE score >119 and plasma TMAO concentration ≤3.7 μmol/L. TMAO levels showed association with poor prognosis (death/MI) at 2 years and superiority over contemporary biomarkers for patients hospitalized due to acute MI. Furthermore, when used with the GRACE score for calculating risk at 6 months, TMAO reidentified patients at lower risk after initial categorization into a higher-risk group and showed usefulness as a secondary risk stratification biomarker.

How reliable is secondary risk stratification with stimulated thyroglobulin in patients with differentiated thyroid carcinoma?

SummaryObjective: Primary risk factors in patients with differentiated thyroid carcinoma (DTC) are well established. In our institution, secondary risk stratification has been performed with stimulated Thyroglobulin (sTg; TSH &gt; 30 mIU/l) within six months after primary therapy since 2001. In this study, we evaluated the predictive value of sTg for long-term disease- free survival (DFS). Patients, methods: Data of 202 consecutive patients with DTC were analyzed retrospectively. Median follow-up time was 6.4 years (12 months to 16.2 years). Patients were staged according to Union International Contre le Cancer (UICC) criteria. Primary risk stratification was carried out according to European Thyroid Association criteria. Initially, 134 patients (66%) were classified as low-risk and 68 patients (34%) as high-risk. The influence of established risk factors and sTg on DFS was analyzed at three different time points, up to 36 months after initial therapy. Results: In total, 169 (84%) of all patients remained in complete remission after surgery followed by radioiodine-therapy. Six patients (3%) developed tumour recurrence after initial complete remission. Primary risk factors for persistent disease were male sex, follicular or oncocytic tumour, primary tumour &gt; 4 cm in diameter, initial lymph node involvement, initial metastatic disease and microscopic or macroscopic residual tumor. sTg ≤ 0.3 ng/ml measured within six months after initial therapy was a highly significant predictor (p ≤ 0.001) for lasting DFS, 99% of patients with sTg ≤ 0.3 ng/ml were in complete remission 36 months after initial therapy. Conclusions: A stimulated Tg ≤ 0.3 ng/ml within six months after initial therapy is a reliable predictor for long-term disease- free survival independent of primary risk stratification.

New directions in cardiovascular risk assessment: the role of secondary risk stratification markers

Cardiovascular disease (CVD) risk screening is performed by multivariate methods relying on calculators derived from the Framingham study, other epidemiological studies or primary care records. However, it only identifies 70% of individuals at risk for CVD events and there has been interest in adding other risk factors to improve its predictive capacity. The addition of a family history of premature CVD is well established and there is evidence for adding lipoprotein (a) in some populations and possibly C-reactive protein may be suitable for general use in CVD risk assessment. Most new biochemical and imaging markers have been assessed in the context of improving risk classification in intermediate-risk groups rather than in the general population. There is evidence that N-terminal pro-B-type natriuretic peptide and coronary artery calcium score add significantly to risk prediction. The data for carotid intima-media thickness, ankle-brachial index are less strong and high sensitivity troponins look promising, but have had only limited data to date. Large scale meta-analyses ideally of pooled primary patient data will be required to determine the best additional markers to add to conventional risk prediction and in what groups to apply them.

Midregional Proadrenomedullin for Prediction of Cardiovascular Events in Coronary Artery Disease: Results from the AtheroGene Study

Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR-proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation. We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years. The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individuals presenting with SAP had only slightly lower plasma MR-proADM concentrations than those with ACS (0.53 vs 0.55 nmol/L, P=0.006). MR-proADM showed a moderate association with age, serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, serum C-reactive protein, hypertension, diabetes, and prevalent multivessel disease (all P<0.0005). Individuals suffering from a cardiovascular event had higher MR-proADM concentrations at baseline in both groups (SAP 0.63 vs 0.53 nmol/L and ACS 0.65 nmol/L vs 0.55 nmol/L, both P<0.0005). Cox regression analysis incorporating various variables of cardiovascular risk and NT-proBNP revealed a hazard ratio of 1.4 (95% CI 1.2-1.6; P<0.0005) per increment of MR-proADM by 1SD. In risk models for secondary prevention, MR-proADM provided information comparable to that of NT-proBNP. MR-proADM is an independent predictor for future cardiovascular events in patients with symptomatic coronary artery disease, providing information comparable to NT-proBNP for secondary risk stratification.

Medical management of thyroid cancer: a risk adapted approach

Risk adapted treatment recommendations are dependent on accurate predictions of the risk of recurrence, risk of death, and likely sites of recurrence. When combined with response to therapy assessments and secondary risk stratification during follow-up, this risk adapted approach will allow the clinician to tailor the aggressiveness of therapy and follow up to the risk of recurrence and death in individual patients.

Risk assessment in the patient with established peripheral arterial disease

Office-based cardiovascular risk prediction continues to challenge practitioners in primary and secondary risk stratification settings. In patients with established peripheral arterial disease (PAD), the risk of cardiovascular events (i.e. death or morbidity due to coronary heart disease and/or cerebrovascular disease) is high, yet traditional risk factors and the ankle-brachial index (ABI) do not provide a complete secondary risk prediction. In this population, office-based cardiovascular risk stratification may be improved by surrogate markers of the systemic atherosclerotic burden, as well as markers of systemic inflammation. This review will evaluate the utility of the ABI, clinical stage of disease, and the emerging role of C-reactive protein (CRP) and other inflammatory markers in secondary risk prediction in PAD. Defining which patients are in the highest category of risk may direct health care providers to emphasize secondary preventive measures, and facilitate patient adherence to recommended medical therapies and smoking cessation.