MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation: The ARIC Study.

BACKGROUND: MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease. METHODS: Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (<50%), AF, and coronary heart disease. Mediation of the association between MMP-2 and HF was assessed by censoring participants who developed AF or coronary heart disease before HF. Multivariable linear regression models were used to assess associations of MMP-2 with measures of left ventricular and left atrial structure and function. RESULTS: Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21-1.81]), incident HF with preserved ejection fraction (1.44 [95% CI, 1.07-1.94]), incident heart failure with reduced ejection fraction (1.48 [95% CI, 1.08-2.02]), and incident AF (1.44 [95% CI, 1.18-1.77]) but not incident coronary heart disease (0.97 [95% CI, 0.71-1.34]). Censoring AF attenuated the MMP-2 association with HF with preserved ejection fraction. Higher plasma MMP-2 levels were associated with larger left ventricular end-diastolic volume index, greater left ventricular mass index, higher E/e' ratio, larger left atrial volume index, and worse left atrial reservoir and contractile strains (all P<0.001). CONCLUSIONS: Higher plasma MMP-2 levels associate with diastolic dysfunction, left atrial dysfunction, and a higher risk of incident HF and AF. AF is a mediator of MMP-2-associated HF with preserved ejection fraction risk.

Dietary Effects on Monocyte Phenotypes in Subjects With Hypertriglyceridemia and Metabolic Syndrome.

In patients with hypertriglyceridemia, a short-term low-saturated fat vs high-saturated fat diet induced lower plasma lipids and improved monocyte phenotypes. These findings highlight the role of diet fat content and composition for monocyte phenotypes and possibly cardiovascular disease risk in these patients. (Effects of Dietary Interventions on Monocytes in Metabolic Syndrome; NCT03591588).

Utilization Rates of SGLT2 Inhibitors Among Patients With Type 2 Diabetes, Heart Failure, and Atherosclerotic Cardiovascular Disease: Insights From the Department of Veterans Affairs.

BACKGROUND: Multiple clinical trials have demonstrated significant cardiovascular benefit with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2DM) and heart failure (HF) irrespective of ejection fraction. There are limited data evaluating real-world prescription and practice patterns of SGLT2 inhibitors. OBJECTIVES: The authors sought to assess utilization rates and facility-level variation in the use among patients with established atherosclerotic cardiovascular disease (ASCVD), HF, and T2DM using data from the nationwide Veterans Affairs health care system. METHODS: The authors included patients with established ASCVD, HF, and T2DM seen by a primary care provider between January 1, 2020, and December 31, 2020. They assessed the use of SGLT2 inhibitors and the facility-level variation in their use. Facility-level variation was computed using median rate ratios, a measure of likelihood that 2 random facilities differ in use of SGLT2 inhibitors. RESULTS: Among 105,799 patients with ASCVD, HF, and T2DM across 130 Veterans Affairs facilities, 14.6% received SGLT2 inhibitors. Patients receiving SGLT2 inhibitors were younger men with higher hemoglobin A1c and estimated glomerular filtration rate and were more likely to have HF with reduced ejection fraction and ischemic heart disease. There was significant facility-level variation of SGLT2 inhibitor use, with an adjusted median rate ratio of 1.55 (95% CI: 1.46-1.64), indicating a 55% residual difference in SGLT2 inhibitor use among similar patients with ASCVD, HF, and T2DM receiving care at 2 random facilities. CONCLUSIONS: Utilization rates of SGLT2 inhibitors are low in patients with ASCVD, HF, and T2DM, with high residual facility-level variation. These findings suggest opportunities to optimize SGLT2 inhibitor use to prevent future adverse cardiovascular events.

What is really new in triglyceride guidelines?

PURPOSE OF REVIEW: In this review, we will summarize some of the landmark clinical trials of triglyceride-lowering therapies and review updates in clinical guidelines with regards to treatment of elevated triglyceride levels. RECENT FINDINGS: Accumulating evidence from epidemiologic and Mendelian randomization studies has shown that triglyceride and are causally linked to atherosclerotic cardiovascular disease (ASCVD) and contribute to atherosclerosis. However, most clinical trials evaluating use of triglyceride-lowering therapies, including fibrates, niacin and fish oils [combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have not been able to demonstrate significant cardiovascular risk reduction. REDUCE-IT is the only randomized clinical trial that showed significant cardiovascular benefit with the use of icosapent ethyl esters (a purified EPA), in patients with ASCVD or diabetes with elevated risk on maximally tolerate statin. SUMMARY: Current guidelines and expert consensus documents from multiple societies strongly endorse therapeutic lifestyle interventions to effectively lower TG as the first-line therapy for treatment of hypertriglyceridemia. Evaluation and treatment of secondary causes of hypertriglyceridemia including optimal glycaemic control is crucial. Statins lower ASCVD risk in patients with elevated triglycerides and are first-line for treatment of elevated triglyceride. In a patient with residual mild to moderate hypertriglyceridemia on maximally tolerate statin and elevated cardiovascular risk icosapent, ethyl ester may be used for further ASCVD risk reduction.

South Asian ethnicity: What can we do to make this risk enhancer a risk equivalent?

South Asians account for around 25% of the global population and are the fastest-growing ethnicity in the US. This population has an increasing burden of atherosclerotic cardiovascular disease (ASCVD) which is also seen in the diaspora. Current risk prediction equations underestimate this risk and consider the South Asian ethnicity as a risk-enhancer among those with borderline-intermediate risk. In this review, we discuss why the South Asian population is at a higher risk of ASCVD and strategies to mitigate this increased risk.

Healthcare Access Among Individuals of Asian Descent in the U.S.

Introduction: Some groups of Asian Americans, especially Asian Indians, experience higher rates of atherosclerotic cardiovascular disease (ASCVD) compared with other groups in the U.S. Barriers in accessing medical care partly may explain this higher risk as a result of delayed screening for cardiovascular risk factors and timely initiation of preventive treatment. Methods: Cross-sectional data were utilized from the 2006 to 2015 National Health Interview Survey (NHIS). Barriers to accessing medical care included no place to seek medical care when needed, no healthcare coverage, no care due to cost, delayed care due to cost, inability to afford medication, or not seeing a doctor in the past 12 months. Results: The study sample consisted of 18,150 Asian individuals, of whom 20.5% were Asian Indian, 20.5% were Chinese, 23.4% were Filipino, and 35.6% were classified as "Other Asians". The mean (standard error) age was 43.8 (0.21) years and 53% were women. Among participants with history of hypertension, diabetes mellitus, or ASCVD (prevalence = 25%), Asian Indians were more likely to report delayed care due to cost (2.58 (1.14,5.85)), while Other Asians were more likely to report no care due to cost (2.43 (1.09,5.44)) or delayed care due to cost (2.35 (1.14,4.86)), compared with Chinese. Results among Filipinos were not statistically significant. Conclusions: Among Asians living in the U.S. with cardiovascular risk factors or ASCVD, Asian Indians and Other Asians are more likely to report delayed care or no care due to cost compared with Chinese.

Potential Impact of 2017 American College of Cardiology/American Heart Association Hypertension Guideline on Contemporary Practice: A Cross-Sectional Analysis From NCDR PINNACLE Registry.

Background Clinical implications of change in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the diagnosis and management of hypertension, compared with recommendations by 2014 expert panel and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), are not known. Methods and Results Using data from the NCDR (National Cardiovascular Data Registry) PINNACLE (Practice Innovation and Clinical Excellence) Registry (January 2013-Decemver 2016), we compared the proportion and clinical characteristics of patients seen in cardiology practices diagnosed with hypertension, recommended antihypertensive treatment, and achieving blood pressure (BP) goals per each guideline document. In addition, we evaluated the proportion of patients at the level of practices meeting BP targets defined by each guideline. Of 6 042 630 patients evaluated, 5 027 961 (83.2%) were diagnosed with hypertension per the 2017 ACC/AHA guideline, compared with 4 521 272 (74.8%) per the 2014 panel and 4 545 976 (75.2%) per JNC7. The largest increase in hypertension prevalence was seen in younger ages, women, and those with lower cardiovascular risk. Antihypertensive medication was recommended to 70.6% of patients per the ACC/AHA guideline compared with 61.8% and 65.9% per the 2014 panel and JNC7, respectively. Among those on antihypertensive agents, 41.2% achieved BP targets per the ACC/AHA guideline, compared with 79.4% per the 2014 panel and 64.3% per JNC7. Lower proportions of women, non-White (Black and "other") races, and those at higher cardiovascular risk achieved BP goals. Median practice-level proportion of patients meeting BP targets per the 2014 panel but not the ACC/AHA guideline was 37.8% (interquartile range, 34.8%-40.7%) and per JNC7 but not the ACC/AHA guideline was 22.9% (interquartile range, 19.8%-25.9%). Conclusions Following publication of the 2017 guideline, significantly more people, particularly younger people and those with lower cardiovascular risk, will be diagnosed with hypertension and need antihypertensive treatment compared with previous recommendations. Significant practice-level variation in BP control also exists. Efforts are needed to improve guideline-concordant hypertension management in an effort to improve outcomes.

Endpoints in Heart Failure Drug Development.

Heart failure (HF) is a major health problem worldwide. The development of effective drug and/or device therapy is crucial to mitigate the significant morbidity, mortality and healthcare costs associated with HF. The choice of endpoint in clinical trials has important practical and clinical implications. Outcomes of interest including mortality and HF hospitalisations provide robust evidence for regulatory approval granted there is sufficiency of safety data. At the same time, it is important to recognise that HF patients experience significant impairments in functional capacity and quality of life, underscoring the need to incorporate parameters of symptoms and patient-reported outcomes in clinical trials. In this review, the authors summarise the evolution and definition of cardiovascular endpoints used in clinical trials, discuss approaches to study design to allow the incorporation of mortality, morbidity and functional endpoints and, finally, examine the current challenges and suggest steps for the development of cardiovascular endpoints that are effective, meaningful and meet the needs of all relevant stakeholders, including patients, physicians regulators and sponsors.

Triglyceride-rich lipoproteins, apolipoprotein C-III, angiopoietin-like protein 3, and cardiovascular events in older adults: Atherosclerosis Risk in Communities (ARIC) study.

AIMS: Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: In 6359 participants (mean age 75.8 ± 5.3 years) followed for ASCVD events [coronary heart disease (CHD) or ischaemic stroke] up to 6 years, associations between LDL-TG, RLP-C, apoC-III, and ANGPTL3 and ASCVD events were assessed using Cox regression. With adjustment for age, sex, and race, RLP-C, LDL-TG, apoC-III, and ANGPTL3 (as continuous variables) were significantly associated with CHD. However, after adjustment for traditional risk factors and lipid-lowering medications, only LDL-TG and ANGPTL3 were significantly associated with ASCVD events [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.25-2.37 per log unit increase in LDL-TG; HR 1.63, 95% CI 1.17-2.28 per log unit increase in ANGPTL3]. CONCLUSIONS: In older adults, LDL-TG, RLP-C, apoC-III, and ANGPTL3 were associated with CHD events in minimally adjusted models; LDL-TG and ANGPTL3 remained independent predictors of ASCVD events with further adjustment. Future studies should assess potential benefit of lowering hepatic apoC-III or ANGPTL3 expression in patients with elevated triglyceride-rich lipoproteins.

Social Determinants of Health and Comorbidities Among Individuals with Atherosclerotic Cardiovascular Disease: The Behavioral Risk Factor Surveillance System Survey.

Individuals with atherosclerotic cardiovascular disease (ASCVD) often have a high burden of comorbidities. Social determinants of health (SDOH) may complicate adherence to treatment in these patients. This study assessed the association of comorbidities and SDOH among individuals with ASCVD. Cross-sectional data from the 2016 to 2019 Behavioral Risk Factor Surveillance System, a nationally representative US telephone-based survey of adults ages ≥18 years, were used. Cardiovascular comorbidities included hypertension, hyperlipidemia, diabetes mellitus, current cigarette smoking, and chronic kidney disease. Non-cardiovascular comorbidities included chronic obstructive pulmonary disease, asthma, arthritis, cancer, and depression. SDOH associated with being at or above the 75th percentile of comorbidity burden were analyzed using multivariable adjusted logistic regression models. The study population included 387,044 individuals, 9% of whom had ASCVD. The mean (SD) numbers of total, cardiovascular, and non-cardiovascular comorbidities were 1.97 (1.27), 1.28 (0.74), 0.69 (0.91) among those without ASCVD and 3.28 (1.62), 1.73 (0.91), and 1.54 (1.22) among those with ASCVD, respectively (P < 0.001 for all comparisons). Female gender, household income ≤$75,000, being unemployed, and difficulty accessing health care were significantly associated with a higher burden of comorbidities among those with ASCVD. The mean (SD) numbers of comorbidities for those with 0, 1, 2, and ≥3 of the aforementioned SDOH were 2.89 (1.45), 2.86 (1.47), 3.39 (1.58), and 4.01 (1.73), respectively (P < 0.001). Among persons with ASCVD, the burden of cardiovascular and non-cardiovascular comorbidities is directly proportional to SDOH in any given individual. Clinicians should address SDOH when managing high-risk individuals.

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. METHODS: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. RESULTS: Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. CONCLUSION: Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.

Epidemiology and risk factors for stroke in young individuals: implications for prevention.

PURPOSE OF REVIEW: Summarize and examine the epidemiology, etiologies, risk factors, and treatment of stroke among young adults and highlight the importance of early recognition, treatment, and primordial prevention of risk factors that lead to stroke. RECENT FINDINGS: Incidence of stroke, predominantly ischemic, among young adults has increased over the past two decades. This parallels an increase in traditional risk factors such as hypertension, diabetes, and use of tobacco, and use of illicit substances among young stroke patients. Compared to older patients, there is a much higher proportion of intracerebral and subarachnoid hemorrhage in young adults. The cause of ischemic stroke in young adults is also more diverse compared to older adults with 1/3rd classified as stroke of undetermined etiology due to inadequate effort or time spent on investigating these diverse and rare etiologies. Young premature Atherosclerotic Cardiovascular Disease patients have suboptimal secondary prevention care compared to older patients with lower use of antiplatelets and statin therapy and lower adherence to statins. SUMMARY: Among young patients, time-critical diagnosis and management remain challenging, due to atypical stroke presentations, vast etiologies, statin hesitancy, and provider clinical inertia. Early recognition and aggressive risk profile modification along with primary and secondary prevention therapy optimization are imperative to reduce the burden of stroke among young adults and save potential disability-adjusted life years.

Racial Disparities in Modifiable Risk Factors and Statin Usage in Black Patients With Familial Hypercholesterolemia.

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P=0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m2 versus 29±6 kg/m2; P<0.001), hypertension (82% versus 50%; P<0.001), diabetes (39% versus 15%; P<0.001), and current smoking (16% versus 8%; P=0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P=0.004) and other lipid-lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60-1.49; P=0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid-lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

Highlights from Studies Presented at the Virtual American College of Cardiology Scientific Sessions 2021: Staying Updated with the Latest Advancements in Prevention.

PURPOSE OF REVIEW: This review highlights late-breaking science presented at the Virtual American College of Cardiology Scientific Sessions 2021 that demonstrated advancements in preventative cardiology and introduced novel therapeutic modalities for the management of chronic kidney disease, heart failure, and COVID-19. RECENT FINDINGS: The studies reviewed include clinical trials that assessed the use of dapagliflozin in patients with respiratory failure due to COVID-19 (DARE-19 trial); evinacumab for patients with severe hypertriglyceridemia and pancreatitis; effect of genotype-guided oral P2y12 inhibitors vs conventional clopidogrel on long-term ischemic outcomes after percutaneous coronary intervention (TAILOR-PCI trial); anticoagulation in patients hospitalized with COVID-19 (ACTION trial); atorvastatin vs placebo in patients with COVID-19 admitted to the ICU (INSPIRATION-S trial); rehabilitation therapy in older acute heart failure patients (REHAB-HF trial); and aspirin dosing: a patient-centric trial assessing benefits and long-term effectiveness (ADAPTABLE trial). In addition, we review the results of the American College of Cardiology Global Heart Attack Initiative (GHATI). Finally, we discuss the secondary analysis of the STRENGTH trial assessing the association of achieved levels of omega-3 fatty acid levels and major cardiovascular outcomes. The studies presented at the virtual American College of Cardiology Scientific Session 2021 represent remarkable contributions in the field of cardiovascular disease and prevention.

Ten things to know about ten cardiovascular disease risk factors.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The "American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update" is a summary document (updated yearly) regarding CVD risk factors. This "ASPC Top Ten CVD Risk Factors 2021 Update" summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the "ASPC Top Ten CVD Risk Factors 2021 Update" to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.

Premature Atherosclerotic Cardiovascular Disease Risk Among Patients with Inflammatory Bowel Disease.

BACKGROUND: Recent literature has shown an association between atherosclerotic cardiovascular disease and inflammatory bowel disease, potentially mediated through chronic inflammatory pathways. However, there is a paucity of data demonstrating this relationship among young patients with premature atherosclerotic cardiovascular disease. METHODS: Using data from the nationwide Veterans wIth premaTure AtheroscLerosis (VITAL) registry, we assessed the association between extremely premature and premature atherosclerotic cardiovascular disease (age at diagnosis: ≤40 years and ≤55 years, respectively) and inflammatory bowel disease. Patients were compared with age-matched controls without atherosclerotic cardiovascular disease. Multivariable regression models adjusted for traditional risk factors. RESULTS: We identified 147,600 patients and 9485 patients with premature and extremely premature atherosclerotic cardiovascular disease, respectively. Compared with controls, there was a higher prevalence of overall inflammatory bowel disease among premature (0.96% vs 0.84%; odds ratio [OR] 1.14; 95% confidence interval [CI], 1.08-1.21) and extremely premature (1.36% vs 0.75%; OR 1.82; 95% CI, 1.52-2.17) patients. After adjustment, these associations attenuated in both premature and extremely premature groups (OR 1.07; 95% CI, 1.00-1.14 and OR 1.61; 95% CI, 1.34-1.94, respectively). CONCLUSION: Inflammatory bowel disease is associated with higher odds of extremely premature atherosclerotic cardiovascular disease, especially for those age ≤40 years. With increasing age, this risk is attenuated by traditional cardiometabolic factors such as obesity, hypertension, diabetes, smoking, and dyslipidemia. Prospective studies are needed to assess the role of early intervention to decrease cardiovascular risk among young patients with inflammatory bowel disease.

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, and Function, and Cardiovascular Events (from the Atherosclerosis Risk in Communities Study).

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels were associated with significantly higher biomarkers of cardiac injury (high-sensitivity cardiac troponin I and T, N-terminal pro-B-type natriuretic peptide), greater left ventricular mass index, and impaired diastolic function in linear regression analyses, and with increased risk for heart failure hospitalization (adjusted hazard ratio per natural log unit increase [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.58), CVD events (HR 1.34, 95% CI 1.13 to 1.60), and all-cause death (HR 1.26, 95% CI 1.01 to 1.57). In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, left ventricular mass index, impaired diastolic function, CVD, events and all-cause death.

Association of NT-ProBNP, Blood Pressure, and Cardiovascular Events: The ARIC Study.

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk. OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories. METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors. RESULTS: There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg. CONCLUSIONS: Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.