Greater Risk Of Cardiovascular Death Research Articles

The Effect of Heat Exposure on Myocardial Blood Flow and Cardiovascular Function.

Heat extremes are associated with greater risk for cardiovascular death. The pathophysiologic mechanisms mediating this association are unknown. To quantify the myocardial blood flow (MBF) requirements of heat exposure. Experimental study. (ClinicalTrials.gov: NCT04549974). Laboratory-based. 61 participants, comprising 20 healthy young adults (mean age, 28 years), 21 healthy older adults (mean age, 67 years), and 20 older adults with coronary artery disease (CAD) (mean age, 70 years). Participants were heated until their core temperature increased 1.5 °C; MBF was measured before heat exposure and at every increase of 0.5 °C in core temperature. The primary outcome was MBF measured by positron emission tomography-computed tomography. Secondary outcomes included heart rate, blood pressure, and body weight change. At a core temperature increase of 1.5 °C, MBF increased in healthy young adults (change, 0.8 mL/min/g [95% CI, 0.5 to 1.0 mL/min/g]), healthy older adults (change, 0.7 mL/min/g [CI, 0.5 to 0.9 mL/min/g]), and older adults with CAD (change, 0.6 mL/min/g [CI, 0.3 to 0.8 mL/min/g]). This represented a 2.08-fold (CI, 1.75- to 2.41-fold), 1.79-fold (CI, 1.59- to 1.98-fold), and 1.64-fold (CI, 1.41- to 1.87-fold) change, respectively, from preexposure values. Imaging evidence of asymptomatic heat-induced myocardial ischemia was seen in 7 adults with CAD (35%) in post hoc analyses. In this laboratory-based study, heating was limited to about 100 minutes and participants were restricted in movement and fluid intake. Participants refrained from strenuous exercise and smoking; stopped alcohol and caffeine intake; and withheld β-blockers, calcium-channel blockers, and nitroglycerin before heating. Heat exposure that increases core temperature by 1.5 °C nearly doubles MBF. Changes in MBF did not differ by age or presence of CAD, but some older adults with CAD may experience asymptomatic myocardial ischemia. Canadian Institutes of Health Research.

Endothelial dysfunction predicts bleeding and cardiovascular death in acute coronary syndrome

BackgroundsRecently, there has been increasing awareness that bleeding may lead to adverse outcomes. Endothelial dysfunction is associated with increased risk of cardiovascular and bleeding events. This study aimed to investigate the association of endothelial dysfunction with major bleeding and specific causes of death in addition to major adverse cardiovascular events in patients with acute coronary syndrome. MethodsThis single-centre retrospective observational study was conducted at a tertiary-care hospital; patients with acute coronary syndrome were included between June 2010 and November 2014 (median follow-up, 6.1 years). The reactive hyperaemia index was assessed before their discharge; reactive hyperaemia index <1.67 was defined as endothelial dysfunction. The main outcomes were the incidence of major bleeding, all-cause death, cardiovascular death, non-cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. ResultsAmong the included 674 patients with acute coronary syndrome, 264 (39.2%) had endothelial dysfunction. Multivariable Cox-hazard analyses revealed an independent predictive value of endothelial dysfunction for major bleeding (hazard ratio 2.29, 95% confidence interval 1.17–4.48, P = 0.016) and major adverse cardiovascular events (hazard ratio 2.04, 95% confidence interval 1.43–2.89, P < 0.001). The endothelial dysfunction group patients had a 2.5-fold greater risk of cardiovascular death; however, no association was found with non-cardiovascular death. ConclusionEndothelial dysfunction assessed using reactive hyperaemia index predicted future major cardiovascular event as well as major bleeding and cardiovascular death in patients with acute coronary syndrome.

790 LEFT VENTRICULAR OUTFLOW TRACT VELOCITY TIME INTEGRAL OUTPERFORMS LEFT VENTRICULAR EJECTION FRACTION IN HEART FAILURE PATIENTS WITH SIGNIFICANT MITRAL REGURGITATION

Abstract Background Reduced left ventricular ejection fraction (LVEF) has been used as a key criterion for the management of mitral regurgitation (MR) in patients with heart failure (HF), including the decision about mitral valve repair. However, LVEF, not taking into account mitral regurgitant volume, may be an imprecise predictor of outcome in HF patients with MR. Conversely, the estimation of the forward volume through the LV outflow tract (LVOT) may be a better metric in this setting. In this regard, LVOT velocity time integral (LVOT-VTI), not relying on geometrical assumptions, has been shown to be more reproducible than the calculated stroke volume (i.e., LVOT-VTI * LVOT cross sectional area), at least in the acute setting. Objective To assess the prognostic significance of LVOT-VTI in a contemporary cohort of patients with chronic HF and significant MR. Methods Consecutive patients with chronic HF with reduced (≤40%) or mildly reduced (41-49%) LVEF and moderate-to-severe or severe MR, according to the latest European Society of Cardiology criteria, were selected and followed-up for the endpoint of cardiovascular death. Results 203 patients were enrolled in the study (74±11 years, 66% men, 47% ischemic etiology, HFrEF 86%, LVEF 31±9%, mean LVOT-VTI 21±6 cm). Most patients showed a NYHA class II (40%) or III (31%) and received beta-blockers (95%), ACE-inhibitors/ARBs or ARNI (77%), and mineralocorticoid receptor antagonists (82%). Seventy-seven patients (38%) had permanent atrial fibrillation and 46 (23%) a cardiac resynchronization therapy device. Over a median follow-up of 18 (7-33) months, 30 patients died, 24 of whom for a cardiovascular cause, and 10 underwent mitral valve repair/replacement. When stratified according to the optimal prognostic cut-off of LVOT-VTI, patients with a LVOT-VTI &amp;lt;16 cm (n=36) showed the greater risk of cardiovascular death (Log Rank 18.2, p&amp;lt;0.001, Figure). Similarly, patients with a LVEF &amp;lt;33% (n=122) showed a higher risk of cardiovascular death (Log Rank 5.5, p=0.019). Nevertheless, at Cox regression analysis, a unit decrease in LVOT-VTI (hazard ratio, HR 0.87 [95%CI 0.79-0.95], p=0.002) but not in LVEF (p=0.729) was associated with a higher risk of cardiovascular death (Figure). Conclusion Left ventricular forward volume, noninvasively estimated through LVOT-VTI, but not LVEF, predicts the risk of cardiac death in patients with chronic HF and significant MR.

Association of heart rate with cardiovascular events and mortality in hypertensive and normotensive population: a nationwide prospective cohort study.

BackgroundCardiovascular disease is the leading cause of death worldwide. We assessed the association of baseline heart rate with cardiovascular events and mortality in hypertensive and normotensive populations using a prospective urban and rural epidemiology cohort study in China.MethodsA total of 29,554 individuals were involved in our analysis, distributed equally between groups of normotensive and hypertensive. The primary outcomes were myocardial infarction, stroke, major cardiovascular diseases, and cardiovascular mortality. Cox frailty models were utilized to estimate hazard ratios for cardiovascular outcomes, and restricted cubic splines were used to explore the shape of the association between baseline heart rate and cardiovascular mortality.ResultsDuring a total observational time of 230,813 person-years, 402 myocardial infarction events, 1,096 stroke events, 1,540 major cardiovascular events, and 356 cardiovascular deaths were documented. In adjusted analyses, normotensive subjects with baseline heart rate >82.5 beats per minute had a 3.30-fold greater risk of cardiovascular death and an increased 72% risk of myocardial infarction, compared with individuals whose baseline heart rate was 65.5–71 beats per minute. A similar trend was observed for cardiovascular mortality in the hypertensive population, but the association was attenuated. Multivariable-adjusted restricted cubic splines showed linear associations between baseline heart rate and cardiovascular mortality in two groups of people (all P<0.05 for linearity).ConclusionsElevated baseline heart rate is associated with an increased risk of cardiovascular mortality and myocardial infarction in the normotensive population. The association is attenuated for cardiovascular death in hypertensive patients.

Abstract 14254: Pharmacodynamic Effects of a Single Dose of CK-3773274 in Cats With Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy in the absence of known causes. HCM can be due to genetic mutations that affect sarcomeric proteins, leading to myocardial hypercontractility. HCM is often complicated by left ventricular outflow tract obstruction (LVOTO) and patients may be at greater risk of cardiovascular death. Medications targeted to address the pathophysiology of HCM and ameliorate LVOTO are needed. CK-3773274 (CK-274) is a novel small molecule cardiac myosin inhibitor that reduces myocardial contractility in vitro and in vivo . Cats have naturally occurring HCM commonly complicated by LVOTO and are an excellent large animal model for investigation of HCM therapeutics. In this study, we aim to characterize the pharmacodynamic effect of a single oral dose of CK-274 on cardiac function in cats with hypertrophic cardiomyopathy and LVOTO. Methods: Eight purpose-bred cats with naturally occurring HCM and LVOTO due to the A31P mutation in cardiac myosin binding protein C (cMyBP-C) were included in a randomized, controlled, crossover study. Cats were randomized to receive vehicle, 0.3 mg/kg, or 1 mg/kg CK-274 treatment, and received echocardiograms at baseline, 6, 24, and 48 hours post-treatment. All cats were crossed over to all treatment groups. Results: CK-274 (1 mg/kg) reduced mean LV fractional shortening at 6, 24 and 48 hours post-treatment (mean reduction 13.6%, p=0.03; 15.4%, p=0.01; 11.6% p=0.02, respectively). CK-274 (1 mg/kg) increased LV systolic internal dimension at 6 and 24-hours post-treatment (mean increase 0.21 cm, p=0.046; 0.25 cm, p=0.03), and did not affect LV diastolic internal dimension. LVOT peak pressure gradient was reduced with CK-274 (0.3 mg/kg) treatment [median pressure gradient at baseline 27.1 mmHg (IQR 18.3-33.3) vs 24 hours post-drug, 7.3 mmHg (IQR 14.2-19.7) p=0.01]. Heart rate did not change for any treatment group over time. No differences were noted following vehicle administration at any time point. Conclusion: In HCM affected cats with the cMyBP-C A31P mutation, the cardiac myosin inhibitor CK-274 is well tolerated at the studied doses and caused dose-related changes in LV systolic function and reductions in LVOT peak pressure gradient.

Myocardial Infarction in Heart Failure With Preserved Ejection Fraction: Pooled Analysis of 3 Clinical Trials

ObjectivesThe authors investigated the relationship between past or incident myocardial infarction (MI) and cardiovascular (CV) events in heart failure with preserved ejection fraction (HFpEF). BackgroundMI and HFpEF share some common risk factors. The prognostic significance of MI in patients with HFpEF is uncertain. MethodsThe authors pooled data from 3 trials—CHARM Preserved (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity), I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function), and the Americas region of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) (N = 8,916)—and examined whether MI before or following enrollment independently predicted CV death and heart failure (HF) hospitalization. ResultsAt baseline, 2,668 patients (30%) had history of MI. Prior MI was independently associated with greater risk of CV death (4.7 vs. 3.5 events/100 patient-years [py], adjusted hazard ratio [HR]: 1.42 [95% confidence interval (CI): 1.23 to 1.64]; p < 0.001). Excess sudden death drove this difference (1.9 vs. 1.2 events/100 py, adjusted HR: 1.55 [95% CI: 1.23 to 1.97]; p < 0.001). There was no difference in HF hospitalization (5.9 vs. 5.5 events/100 py, adjusted HR: 1.05, 95% CI: 0.92 to 1.19) or HF death by prior MI. During follow-up, MI occurred in 336 patients (3.8%). Risk of CV death increased 31-fold in the first 30 days after first post-enrollment MI, and remained 58% higher beyond 1 year after MI. Risk of first or recurrent HF hospitalization increased 2.4-fold after MI. ConclusionsPrior MI in HFpEF is associated with greater CV and sudden death but similar risk of HF outcomes. Patients with HFpEF who experience MI are at high risk of subsequent CV death and HF hospitalization. These data highlight the importance of primary and secondary prevention of MI in patients with HFpEF. (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM Preserved]; NCT00634712; Irbesartan in Heart Failure With Preserved Systolic Function [I-Preserve]; NCT00095238; and Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)

Lowered anti-beta1 adrenergic receptor antibody concentrations may have prognostic significance in acute coronary syndrome

Although several risk factors exist for acute coronary syndrome (ACS) no biomarkers for survival or risk of re-infarction have been validated. Previously, reduced serum concentrations of anti-ß1AR Ab have been implicated in poorer ACS outcomes. This study further evaluates the prognostic implications of anti-ß1AR-Ab levels at the time of ACS onset. Serum anti-ß1AR Ab concentrations were measured in randomly selected patients from within the PLATO cohort. Stratification was performed according to ACS event: ST-elevation myocardial infarct (STEMI) vs. non-ST elevation myocardial infarct (NSTEMI). Antibody concentrations at ACS presentation were compared to 12-month all-cause and cardiovascular mortality, as well as 12-month re-infarction. Sub-analysis, stratifying for age and the correlation between antibody concentration and conventional cardiac risk-factors was subsequently performed. Serum anti-ß1AR Ab concentrations were measured in 400/799 (50%) STEMI patients and 399 NSTEMI patients. Increasing anti-ß1AR Ab concentrations were associated with STEMI (p = 0.001). Across all ACS patients, no associations between anti-ß1AR Ab concentration and either all-cause cardiovascular death or myocardial re-infarction (p = 0.14) were evident. However among STEMI patients ≤60 years with anti-ß1AR Ab concentration <median higher rates of re-infarction were observed, compared to those with anti-ß1AR Ab concentrations > median (14/198 (7.1%) vs. 2/190 (1.1%)); p = 0.01). Similarly, the same sub-group demonstrated greater risk of cardiovascular death in year 1, including re-infarction and stroke (22/198 (11.1%) vs. 10/190 (5.3%); p = 0.017). ACS Patients ≤60 years, exhibiting lower concentrations of ß1AR Ab carry a greater risk for early re-infarction and cardiovascular death. Large, prospective studies quantitatively assessing the prognostic relevance of Anti-ß1AR Ab levels should be considered.

Prior and Incident Myocardial Infarction in HFpEF: A Pooled, Patient-Level Analysis of 3 Contemporary Clinical Trials with 8,916 Patients

Background Myocardial infarction (MI) and heart failure with preserved ejection fraction (HFpEF) share common risk factors. Little is known about the prognostic significance of remote or recent MI in patients with HFpEF. Methods We pooled data from 3 trials: CHARM-Preserved, I-Preserve, and Americas region of TOPCAT (n=8,916), and examined whether prior (before randomization) and post randomization MI predicted cardiovascular (CV) death using multivariable Cox proportional hazards models accounting for 31 clinically relevant covariates. Results At baseline, 2,668 patients (30%) had a history of MI. Prior MI was independently associated with a greater risk of CV death (adj. HR 1.42, 95% CI 1.23-1.64) (Panel A). During follow-up, MI occurred in 338 patients (3.8%), 2 of whom died the same day. In the first 30 days after first post-randomization MI, risk of CV death increased 34-fold, and remained 58% higher 1 year after MI (Panel B). Conclusion In patients with HFpEF who experience MI, risk of CV death is very high in the early period and remains elevated at 1 year. Prevention of MI in HFpEF may represent an under-recognized therapeutic goal.

Cardiovascular impact of PM2.5 from the emissions of coal-fired power plants in Spain during 2014

Introduction and objectivesOne of the main sources of energy in Spain is still coal combustion. It releases multiple pollutants into the atmosphere, such as PM2.5, that has been linked to an increase in cardiovascular morbidity and mortality. The objectives of this paper are: (1) to determine the national distribution of these particles and their proximity to coal plants, (2) to estimate the cardiovascular impact of PM2.5 particles in Spain in 2014. MethodsIn order to complete the national pollutant dispersion study, we used the CALPUFF model. The epidemiologic and demographic data were obtained from the National Statistics Institute. The associations “pollutant-effect” were obtained by internationally validated methodologies. ResultsThe total number of deaths due to coal pollutants were 709, from which 586 (82.6%) were related to PM2.5 particles. Most of them were due to myocardial infarctions, fatal strokes and heart failure, adding up to 170 cases of mortality related to PM2.5 (29%). The greatest densities were found in the regions of Asturias and Castilla y León. ConclusionsThis study describes an increase in cardiovascular mortality and morbidity in Spain, due to coal combustion pollutants. It finds a greater impact in the provinces of Asturias and Castilla y León, where a higher presence of coal power plants can be found. This reflects that the people that live in those areas have a greater risk of cardiovascular death due to PM2.5 pollutant exposure from coal.

Impacto cardiovascular del PM2,5 procedente de las emisiones de las centrales térmicas de carbón en España durante el año 2014

Introduction and objectivesOne of the main sources of energy in Spain is still coal combustion. It releases multiple pollutants into the atmosphere, such as PM2.5, that has been linked to an increase in cardiovascular morbidity and mortality. The objectives of this paper are: 1) to determine the national distribution of these particles and their proximity to coal plants, 2) to estimate the cardiovascular impact of PM2.5 particles in Spain in 2014. MethodsIn order to complete the national pollutant dispersion study, we used the CALPUFF model. The epidemiologic and demographic data were obtained from the National Statistics Institute. The associations «pollutant-effect» were obtained by internationally validated methodologies. ResultsThe total number of deaths due to coal pollutants were 709, from which 586 (82.6%) were related to PM2.5 particles. Most of them were due to myocardial infarctions, fatal strokes and heart failure, adding up to 170 cases of mortality related to PM2.5 (29%). The greatest densities were found in the regions of Asturias and Castilla y León. ConclusionsThis study describes an increase in cardiovascular mortality and morbidity in Spain, due to coal combustion pollutants. It finds a greater impact in the provinces of Asturias and Castilla León, where a higher presence of coal power plants can be found. This reflects that the people that live in those areas have a greater risk of cardiovascular death due to PM2.5 pollutant exposure from coal.

Temporal Biomarker Profiling Reveals Longitudinal Changes in Risk of Death or Myocardial Infarction in Non-ST-Segment Elevation Acute Coronary Syndrome.

There are conflicting data on whether changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are associated with a change in prognosis. We measured NT-proBNP and hs-CRP at 3 time points in 1665 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Cox proportional hazards was applied to the delta between temporal measurements to determine the continuous association with cardiovascular events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40% increase as the basic unit of temporal change. Median NT-proBNP was 370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0 (111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and 1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas between baseline and 6 months were the most prognostically informative. Every +40% increase of delta NT-proBNP (baseline to 6 months) was associated with a 14% greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI, 1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95% CI, 1.04-1.26), while every +40% increase of delta hs-CRP (baseline to 6 months) was associated with a 9% greater risk of the composite end point (adjusted HR 1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction (adjusted HR 1.10, 95%, CI 1.00-1.20). Temporal changes in NT-proBNP and hs-CRP are quantitatively associated with future cardiovascular events, supporting their role in dynamic risk stratification of NSTEACS. ClinicalTrials.gov identifier NCT00699998.

L'utilizzo del Test di Screening Nutrizionale Malnutrition Inflammation Score (MIS) in Dialisi

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The use of the Nutritional Screening Test Malnutrition Inflammation Score (MIS) in Dialysis

Protein-energy malnutrition is one of the most common complications in chronic renal failure patients who are treated with hemodialysis, especially in the elderly and in patients who have a long dialysis history. Protein-energy malnutrition is associated with higher rates of mortality and morbidity, and also with a greater risk of cardiovascular death in dialysis patients. The importance of nutritional status evaluation and treatment is underlined by some guidelines, such as Kidney Disease Outcomes Quality Initiative. Nutritional screening should be an easy and fast tool that should be undertaken during the first meeting with the patient and when the patient is hospitalized or registered in other institutions. Scientific literature (see for example Kalantar-Zadeh et al) shows that Malnutrition Inflammation Score (MIS) seems to have a high capability in discriminating malnutrition, inflammatory status and anemia and that it seems to be highly predictive for morbidity (number of hospitalizations) and mortality. The objectives of these studies were the perspective of the administration of the MIS to a group of patients treated with hemodialysis in the SCUD (Departmental and University Complex Structure) of Dialysis and Nephrology of Saint Giovanni Bosco Hospital in Turin and the evaluation of the nutritional intervention effects. One of the goal of this study was the involvement of registered nurses, under the coordination of the registered dietitian, in order to have an integrated approach to the problem. In our experience, the monitoring of patients treated with hemodialysis who have been screened to evaluate their nutritional status with an easy and repeatable procedure allows to express some considerations. If we keep in mind the common shortage of registered dietitians in dialysis units, being able to engage registered nurses trained and sensible to the problem of malnutrition, it represents a useful tool to improve the quality of dialysis patients life. Being aware of the MIS is an added value to the professional knowledge of the registered nurses in dialysis units and even more when a professional relation is created between the registered dietitian and the medical doctor involved. Focusing on malnutrition becomes essential because of the changing of the population in dialysis we are observing and for this reason it is important to have and use low-cost screening procedures. The experience of the Dietetic and Clinical Nutrition Unit and of the Dialysis Unit is a very positive one, thanks to the sharing of this project that highlights a multidisciplinary and multiprofessional approach.

Impact of low preprocedural transvalvular gradient on cardiovascular mortality following TAVI: an analysis from the FRANCE 2 registry.

To assess the relationship between a low preprocedural (<40 mmHg) mean transaortic gradient (MTG) and cardiovascular mortality following transcatheter aortic valve implantation (TAVI). We studied highly symptomatic patients at high surgical risk who underwent TAVI, included in the FRANCE 2 multicentre registry. The primary endpoint was the incidence of any cardiovascular death in the year following the procedure. N=3,933 patients (age=82.8±7.2 years; EuroSCORE=21.8±14.1; left ventricular ejection fraction [LVEF]=55.5±12.6%) were enrolled. Low MTG was present in 23.5% of the cases. The one-year cardiovascular mortality was 13.3%. Cardiovascular survival was significantly lower in low MTG patients compared to the others. Multivariable Cox regression analysis revealed that a low MTG independently predicted cardiovascular death (HR=1.53 [1.15-2.04], p=0.004). Other independent predictors of cardiovascular mortality included preprocedural angina (HR=3.12 [1.64-5.96], p=0.0006); NYHA functional Class III-IV (HR=1.57 [1.07-2.29], p=0.02); severe renal failure (HR=1.50 [1.01-2.24], p=0.04); EuroSCORE (HR=1.01 [1.00-1.02], p=0.01); transapical access (HR=1.59 [1.14-2.22], p=0.006); impaired LVEF (HR=1.66 [1.23-2.27], p=0.0007) and post-procedural moderate to severe periprosthetic regurgitation (HR=2.13 [1.56-2.92], p<0.0001). Presence of a low MTG prior to TAVI was associated with a greater risk of cardiovascular death up to one year following the procedure and could be used to identify patients at high risk for adverse cardiovascular outcomes following TAVI.

Added Predictive Value of Night-Time Blood Pressure Variability for Cardiovascular Events and Mortality

The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median follow-up was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P &lt;0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P &lt;0.001/diastolic, P &lt;0.0001), cardiovascular mortality ( P =0.008/&lt;0.0001), and cardiovascular events ( P &lt;0.001/&lt;0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of &lt;12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P &lt;0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables.

A Reverse Dipping Pattern Predicts Cardiovascular Mortality In a Clinical Cohort

An abnormal dipping pattern in ambulatory blood pressure monitoring (ABPM) is a cardiovascular (CV) risk factor. However, its impact on CV mortality has not been investigated sufficiently in clinical practice to be considered a standard parameter. We assessed the association between abnormal dipping patterns and increased CV mortality in a tertiary hospital in Korea. Our retrospective cohort study included 401 patients who underwent ABPM between 1994 and 1996 in Hanyang University Hospital, Seoul, Korea. The patients were classified as risers (<0% drop in systolic BP; n=107), and others included dippers and non-dippers (≥0% drop, n=294). The follow-up period was 120 months. The frequency of CV mortality was 14.0% in risers and 5.8% in others. A Cox regression analysis found a significant association between dipping pattern and CV mortality, after adjusting for age, gender, body mass index, hypertension, diabetes mellitus, smoking and hypercholesterolemia. Risers were at greater risk of CV death than others (RR, 3.02, P=0.022), but there was no difference in event rates between dippers and non-dippers. The reverse dipping pattern may be more frequent in clinical settings than in the population at large, and it is strongly associated with increased risk of CV mortality in Korea.

Association Between Chronic Kidney Disease Detected Using Creatinine and Cystatin C and Death and Cardiovascular Events in Elderly Mexican Americans: The Sacramento Area Latino Study on Aging

Creatinine, the current clinical standard to detect chronic kidney disease (CKD), is biased by muscle mass, age and race. The authors sought to determine whether cystatin C, an alternative marker of kidney function less biased by these factors, can identify elderly Mexican Americans with CKD who are at high risk for death and cardiovascular disease. Longitudinal, with mean follow-up of 6.8 years. Sacramento Area Latino Study of Aging (SALSA). One thousand four hundred and thirty five Mexican Americans aged 60 to 101. Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was determined according to creatinine (eGFRcreat) and cystatin C (eGFRcys), and participants were classified into four mutually exclusive categories: CKD neither (eGFRcreat ≥60 mL/min per 1.73 m(2); eGFRcys ≥60 mL/min per 1.73 m(2)), CKD creatinine only (eGFRcreat <60 mL/min per 1.73 m(2); eGFRcys ≥60 mL/min per 1.73 m(2)), CKD cystatin only (eGFRcreat ≥60 mL/min per 1.73 m(2); eGFRcys <60), and CKD both (eGFRcreat <60 mL/min per 1.73 m(2); GFRcys <60 mL/min per 1.73 m(2)). The associations between each CKD classification and all-cause death and cardiovascular (CV) death were studied using Cox regression. At baseline, mean age was 71 ± 7; 481 (34%) had diabetes mellitus, and 980 (68%) had hypertension. Persons with CKD both had higher risk for all-cause (HR = 2.30, 95% confidence interval (CI) = 1.78-2.98) and CV disease (CVD) (HR = 2.75, 95% CI = 1.96-3.86) death than CKD neither after full adjustment. Persons with CKD cystatin C only were also at greater risk of all-cause (HR = 1.91, 95% CI = 1.37-2.67) and CV (HR = 2.56, 95% CI = 1.64-3.99) death than CKD neither. In contrast, persons with CKD creatinine only were not at greater risk for CV death (HR = 1.39, 95% CI = 0.71-2.72) but were at higher risk for all-cause death (HR = 1.95, 95% CI = 1.27-2.98). Cystatin C may be a useful alternative to creatinine for detecting high risk of death and CVD in elderly Mexican Americans with CKD.

Determinants of Cardiovascular and All-Cause Mortality in Northwest Russia: A 10-Year Follow-Up Study

To study conventional and novel risk factors associated with high cardiovascular disease (CVD) and all-cause mortality in Russia. A prospective cohort study of 3704 adults was performed in Arkhangelsk. The baseline examination was conducted in 1999-2000. The average follow-up was 10.2 years. Information on lifestyle and marital, educational, and psychosocial status was self-reported in a questionnaire. Data on risk factors were collected in a medical examination that included the drawing of blood samples. By October 2010 a total of 147 male and 95 female deaths had occurred. In 59 male and 20 female deaths in which a diagnosis was made by a forensic pathologist, the autopsy data were studied to extract information on post-mortem blood alcohol concentration. A positive blood alcohol concentration was found in 21 (36%) male and 6 (30%) female forensic autopsies. Women reporting consumption of at least 80 g of alcohol monthly and consumption of 5 or more alcohol units during one drinking episode had a greater risk of cardiovascular death than abstainers; relative risk (RR) was 5.06 (95% confidence interval [95% CI], 1.54-16.7) and 3.21 (95% CI, 1.07-9.58), respectively. ApoB/ApoA1-ratio was the strongest predictor of CVD and all-cause death in men (RR, 7.62; 95% CI, 3.15-18.4; and RR, 4.39; 95% CI, 2.22-8.68, respectively) and CVD death in women (RR 3.12; 95% CI, 1.08-8.98). Men who were obese and had obtained a university education had a 40% lower risk of all-cause death. Low serum albumin was associated with high mortality in both genders. Hazardous alcohol consumption is an independent risk factor of CVD mortality in women. The mechanisms behind its damaging effect are not yet clear. Nutritional factors such as serum albumin are important predictors of all-cause mortality in both genders.

Role of Elevated Heart Rate in the Development of Cardiovascular Disease in Hypertension

That elevated heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in healthy people as well as in patients with cardiac diseases is supported by numerous epidemiological association studies.1–4 Increased HR has been recognized as a negative prognostic factor independent of many other clinical parameters that can influence the HR, including physical activity scores, left ventricular function, or use of β-blockers. Thus, HR appears to satisfy all epidemiological criteria for being considered as a true risk factor, and its predictive value for cardiovascular disease appeared to be as strong as that of most important cardiovascular risk factors. This is particularly true for the results obtained in hypertensive patients. Elevated HR is a common feature among hypertensive individuals.1 Among the young hypertensive subjects participating in the HARVEST study, >15% had a baseline resting HR ≥85 bpm and 27% had a HR ≥80 bpm.5 According to the Tensiopulse study, which evaluated 38 145 patients cared for by 2000 general practitioners all across Italy, >30% of the hypertensive patients had a resting HR ≥80 bpm.6 In a large French population, untreated hypertensive subjects had approximately a 6-bpm faster HR than normotensive individuals.7 Elevated HR is frequently associated with high blood pressure (BP) and metabolic disturbances and increases the risk of new onset hypertension and diabetes.1 Many experimental data obtained both in animals and in human beings support the importance of HR as a true risk factor for atherosclerosis and cardiovascular disease, providing convincing evidence for this pathogenetic mechanism.1–3 The pathogenetic connection between HR and cardiovascular disease has been discussed in several reports1–3,8,9 and is beyond the scope of this review. ### High HR as a Precursor of Hypertension, Obesity, and Diabetes Numerous studies have demonstrated that tachycardia is frequently associated with hypertension in …

All-cause and cardiovascular mortality in relation to changing heart rate during treatment of hypertensive patients with electrocardiographic left ventricular hypertrophy

Although higher heart rate (HR) at baseline has been associated with an increased risk of cardiovascular (CV) and all-cause mortality, the relationship of in-treatment HR over time to mortality in hypertensive patients with ECG left ventricular hypertrophy (LVH) has not been examined. Heart rate was evaluated over time in 9190 hypertensive patients treated with losartan- or atenolol-based regimens and followed with annual ECGs. During a mean follow-up of 4.8 ± 0.9 years, 814 patients (8.9%) died, 438 (4.8%) from CV causes. In univariate Cox analyses, every 10 bpm higher HR on in-treatment ECGs was associated with a 25% increased risk of CV death [95% confidence interval (CI): 14-32%] and a 27% greater risk of all-cause mortality (95% CI: 21-34%). In an alternative analysis, persistence or development of a HR ≥ 84 bpm (upper quintile of baseline HR) was associated with an 89% greater risk of CV death (95% CI: 49-141%) and a 97% increased risk of all-cause mortality (95% CI: 65-135%). After adjusting for treatment with losartan vs. atenolol, baseline risk factors for death, baseline HR, baseline and in-treatment systolic and diastolic pressure, incident myocardial infarction, and the known predictive value of baseline and in-treatment QRS duration and ECG LVH, higher in-treatment HR in time-varying multivariable Cox models remained strongly predictive of mortality: every 10 bpm higher HR was associated with a 16% increased adjusted risk of CV mortality (95% CI: 6-27%) and a 25% greater risk of all-cause mortality (95% CI: 17-33%), with persistence or development of a HR ≥ 84 associated with a 55% greater risk of CV death (95% CI: 16-105%) and a 79% greater adjusted risk of all-cause mortality (95% CI: 46-121%). Higher in-treatment HR on serial ECGs predicts greater likelihood of subsequent CV or all-cause mortality, independent of treatment modality, blood pressure lowering, regression of ECG LVH and changing QRS duration in hypertensive patients with ECG LVH. These findings support the value of serial assessment of HR for improved risk stratification in hypertensive patients. http://clinicaltrials.gov/ct/show/NCT00338260?order=1cp.