Bioprosthetic Aortic Valve Thrombosis: Definitions, Clinical Impact, and Management: A State-of-the-Art Review.

Bioprosthetic aortic valve thrombosis is frequently detected after transcatheter and surgical aortic valve replacement due to advances in cardiac computed tomography angiography technology and standardized surveillance protocols in low-surgical-risk transcatheter aortic valve replacement trials. However, evidence is limited concerning whether subclinical leaflet thrombosis leads to clinical adverse events or premature structural valve deterioration. Furthermore, there may be net harm in the form of bleeding from aggressive antithrombotic treatment in patients with subclinical leaflet thrombosis. This review will discuss the incidence, mechanisms, diagnosis, and optimal management of bioprosthetic aortic valve thrombosis after transcatheter aortic valve replacement and bioprosthetic surgical aortic valve replacement.

Markedly elevated high-sensitivity troponin and in-hospital mortality after cardiac surgery.

BACKGROUND: High-sensitivity troponin (hsTnI) is correlated with cardiac mortality; however, studies on the relationship of markedly elevated hsTnI with in-hospital mortality after cardiac surgery are sparse. Therefore, we aimed to define this relationship in order to help guide in-hospital, acute management of post-surgical patients. METHODS: We retrospectively analyzed all cardiac surgeries completed at our institution between January 2020 and June 2022 in which a peak hsTnI was noted to be >35× upper limit of normal (ULN = 34 ng/L). The primary outcome was in-hospital death. Subgroup analysis was performed to assess differences between coronary artery bypass grafting (CABG) and other cardiac surgeries. RESULTS: A total of 1382 cases met inclusion criteria. The patients' mean age was 64.8 years and 68.2 % were male. Median peak hsTnI after surgery was 4202 ng/L (interquartile ratio: 2427-7654). Univariate analysis of troponin level with mortality found that for every 1000 ng/L increase in hsTnI, odds of in-hospital death increased by 3.8 % (odds ratio [OR]: 1.038; 95 % confidence interval [CI] 1.027-1.050; p < 0.0001). In a multivariate model, troponin (OR 1.02; 95 % CI 1.01-1.04; p = 0.004) maintained a significant association with in-hospital death. CABG was associated with a lower risk of in-hospital death for any given hsTnI level up to 60,000 ng/L compared to other cardiac surgeries. CONCLUSION: Increasing hsTnI level is associated with increasing probability of in-hospital mortality and, therefore, serves as an additional, objective measure of risk to help guide in-hospital clinical management.

Gender disparities related to clinical characteristics and outcomes of patients undergoing transseptal procedures.

PURPOSE: Explore gender disparities in patients undergoing transseptal puncture (TSP) for selected transcatheter cardiac intervention procedures. METHODS: Patients who underwent TSP from January 2015 through September 2021 were reviewed. Primary outcomes were procedural and in-hospital major adverse events. Secondary endpoints were procedural success and hospitalization length of stay (LOS) >1 day. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess gender differences for in-hospital adverse events. RESULTS: The study cohort comprised 510 patients (mean [SD] age, 74 [14.0] years); 246 women (48 %) underwent TSP for left atrial appendage occlusion (LAAO) or transcatheter edge-to-edge-repair (TEER). Compared with men, women were younger, had higher CHA2DS2-VASc scores, and were more likely to have had a prior ischemic stroke, but were less likely to have paroxysmal atrial fibrillation. After multivariable adjustment, there were no differences between genders in aborted or canceled procedures (odds ratio [OR]: 0.43; 95 % confidence interval [CI]: 0.10-1.96; p = 0.277), any adverse events (OR: 1.00; 95 % CI: 0.58-1.70; p = 0.98), major adverse events (OR: 1.60; 95 % CI: 0.90-2.80; p = 0.11), or death (OR: 1.00; 95 % CI: 0.20-5.00; p = 0.31). Subgroup analysis for LAAO procedures showed that at 30 days, women had higher rates of adverse events, major adverse cardiac events, and LOS >1 day. CONCLUSIONS: Men and women showed no differences in procedural success and in-hospital adverse outcomes in unadjusted analysis and after multivariable adjustment, despite women having a higher risk profile among patients undergoing TSP. However, compared with men, women undergoing LAAO experienced a higher rate of in-hospital adverse events irrespective of TSP.

Prognostic implication of hemoglobin reduction with and without clinical bleeding after percutaneous coronary intervention in patients with acute coronary syndromes.

BACKGROUND: Bleeding events are associated with higher mortality rates in patients with cardiovascular diseases, including patients presenting with acute coronary syndrome (ACS) undergoing coronary revascularization. We aimed to determine whether a reduction in hemoglobin (Hgb) from pre- to postpercutaneous coronary intervention (PCI), with or without evidence of clinical bleeding, is a correlate of in-hospital mortality for patients presenting with ACS who underwent primary PCI. METHODS: We divided 33816 consecutive patients with ACS who underwent PCI into three categories: (1) target group (defined as Hgb reduction without overt bleeding [n = 112]); (2) Hgb reduction with overt bleeding (n = 48); and (3) control group (defined as no Hgb reduction and no overt bleeding [n = 3156]). Hgb reduction was defined as a drop of >3 g/dL in Hgb value from preprocedure and postprocedure during the index hospitalization. The primary outcome was in-hospital mortality. We used logistic regression to examine the relationship between Hgb reduction with and without bleeding and in-hospital mortality. RESULTS: In crude analysis, the Hgb reduction with overt bleed group had a higher in-hospital mortality rate (16.7%) than the target (9.8%) and control groups (0.6%). Adjusted logistic regression estimates a 0.393 (95% confidence interval [CI]: 0.137, 1.869) odds ratio for in-hospital death of the target group over the Hgb reduction with bleed group, and a 54.517 (95% CI: 2.07, >1000) odds ratio of the target group over the control group. CONCLUSIONS: In patients presenting with ACS undergoing PCI, Hgb reduction with and without overt bleeding were both independently associated with in-hospital mortality.

Impact of IVUS and OCT on physician decision-making during post-PCI optimization.

BACKGROUND: Intravascular imaging (IVI) has been available as a complementary diagnostic tool in addition to coronary angiography for more than two decades. Prior studies have suggested that IVI influences physician decision making in up to 27 % of cases during post-percutaneous coronary intervention (PCI) optimization. However, no studies have compared the two intracoronary imaging modalities (intravascular ultrasound [IVUS] vs. optical coherence tomography [OCT]) in shaping physician decisions post-PCI. METHODS: We retrospectively analyzed IVI studies performed during PCI at a tertiary care center. IVUS and OCT cases performed by a single operator with expertise in both imaging studies were selected. The primary endpoint was the physician reaction rate during post-PCI optimization comparing IVUS vs. OCT. RESULTS: A total of 142 patients underwent IVUS evaluation, and 146 underwent OCT evaluation, post-PCI. The primary endpoint did not differ between IVUS-guided vs OCT-guided PCI optimization (35.2 % vs. 31.5 %, p = 0.505). The predominant cause of abnormalities deemed unsatisfactory by the implanting physician warranting further intervention were stent under-expansion (26.1 % vs. 19.2 %, p = 0.163), followed by malapposition (2.1 % vs. 6.2 %, p = 0.085), and dissection (3.5 % vs 4.1 %, p = 0.794). Overall, IVI using either IVUS or OCT influenced the physician decision in 33.3 % of cases. CONCLUSION: In this first study comparing IVUS- and OCT-guided PCI to assess their impact on physician decision making during post-PCI optimization, the primary endpoint of physician reaction rate was similar for IVUS vs. OCT. The use of post-PCI IVI changed physician management in one third of cases.

Provisional Versus Dual Stenting of Left Main Coronary Artery Bifurcation Lesions (from a Comprehensive Meta-Analysis).

The optimal technique for bifurcation of left main coronary artery (LMCA) stenting has been a subject of controversy since the inception of drug-eluting stents. We searched PubMed, Clinical Trials Registry, and the Cochrane Central Register of Controlled Trials from January 2002 through October 2021. A total of 13 studies comparing the use of provisional versus dual stenting in patients with LMCA bifurcation lesions were included. Any major adverse cardiac event (MACE) was considered the primary composite end point. The secondary end points included individual components of MACE, including death, myocardial infarction, and target lesion revascularization. The treatment effect was defined as the log odds ratio (OR) of provisional over dual stenting for cumulative event rate at 3 years. In 12 studies with 8,377 patients included for MACE, the use of a provisional-stenting strategy was associated with a significant reduction of 3-year MACE (OR 0.64, 95% confidence interval [CI] 0.46 to 0.88) compared with a dual-stenting strategy, primarily driven by target lesion revascularization (OR 0.51, 95% CI 0.36 to 0.73). No significant difference was found regarding death (OR 0.88; 95% CI 0.65 to 1.21) or myocardial infarction (OR 0.97, 95% Cl 0.61 to 1.54). In conclusion, our meta-analysis suggests that provisional stenting should be the preferred technique over dual stenting when treating LMCA bifurcation lesions with drug-eluting stents. Further randomized controlled studies compounded with intracoronary imaging comparing the 2 strategies are warranted.

Overview of FDA Circulatory System Devices Panel virtual meeting on TriGUARD 3 cerebral embolic protection.

Despite advances in transcatheter aortic valve replacement (TAVR) technology, periprocedural stroke remains a complication of TAVR procedures. The TriGUARD 3 device is designed to be positioned in the aortic arch to deflect debris away from the brachiocephalic, left common carotid, and left subclavian arteries during TAVR. The United States Food and Drug Administration (FDA) assembled the Circulatory System Devices Panel to review safety and effectiveness data for the TriGUARD 3 device. Because of the coronavirus disease 2019 pandemic, this meeting was held virtually. In this manuscript, we summarize the data presented by both the sponsor and FDA, as well as the panel discussion.

Alcohol Consumption and Systemic Hypertension (from the Third National Health and Nutrition Examination Survey).

Epidemiological studies have established the association between excessive alcohol consumption and systemic hypertension (SH). However, there are conflicting reports of the association of low to moderate alcohol consumption with SH. The objective of the study was to examine the associations of alcohol consumption and blood pressure categories using the 2017 American College of Cardiology/American Heart Association high blood pressure guidelines. This analysis included 17,059 participants from the Third National Health and Nutrition Examination Survey. Alcohol consumption was ascertained by way of a questionnaire. Blood pressure (mm Hg) was measured during the in-home interview and the participant's visit to the mobile examination center. We used multivariable logistic regression models to examine cross-sectional associations of alcohol consumption and blood pressure categories based on new American College of Cardiology/American Heart Association High Blood Pressure guidelines. Models were adjusted for age, gender, income, and cardiovascular risk factors. Compared with never drinkers, moderate drinkers (7 to 13 drinks/week) had increased odds of prevalent stage 1 and stage 2 SH (odds ratio [95% confidence interval] 1.51 [1.22 to 1.87] and 1.55 [1.20 to 2.00]). Similarly, there were significantly higher odds of prevalent stage 1 and stage 2 SH among heavy drinkers (≥14 drinks/week) (odds ratio [95% confidence interval] 1.65 [1.33 to 2.05] and 2.46 [1.93 to 3.14]). We did not find any association between alcohol consumption and elevated blood pressure category. Response bias must be considered because alcohol consumption was self-reported. Our study indicates the need for further research to understand the potential mechanisms by which alcohol consumption increases the risk of SH. In conclusion, this analysis from a population-based survey showed an association between moderate and heavy alcohol consumption and a higher prevalence of SH.

Relationship of physical function with quality of life in older patients with acute heart failure.

BACKGROUND: Older patients with acute decompensated heart failure (ADHF) have severely impaired physical function (PF) and quality of life (QOL). However, relationships between impairments in PF and QOL are unknown but are relevant to clinical practice and trial design. METHODS: We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. PF measures included Short Physical Performance Battery (SPPB) and 6-min walk distance (6MWD). Disease-specific QOL was assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). General QOL was assessed by the Short Form-12 (SF-12) and EuroQol-5D-5L. PF was evaluated as a predictor of QOL using stepwise regression adjusted for age, sex, race, and New York Heart Association class. RESULTS: Participants were 72 ± 8 years, 54% women, 55% minority race, 52% with reduced ejection fraction, and body mass index 33 ± 9 kg/m2 . Participants had severe impairments in PF (6MWD 185 ± 99 m, SPPB 6.0 ± 2.5 units) and disease-specific QOL (KCCQ Overall Score 41 ± 21 and Physical Score 47 ± 24) and general QOL (SF-12 Physical Score 28 ± 9 and EuroQol Visual Analog Scale 57 ± 23). There were modest, statistically significant correlations between 6MWD and KCCQ Overall, KCCQ Physical Limitation, and SF-12 Physical Scores (r = 0.23, p < 0.001; r = 0.30, p < 0.001; and r = 0.24, p = 0.001, respectively); and between SPPB and KCCQ Physical and SF-12 Physical Scores (r = 0.20, p = 0.004, and r = 0.19, p = 0.007, respectively). Both 6MWD and SPPB were correlated with multiple components of the EuroQol-5D-5L. 6MWD was a significant, weak predictor of KCCQ Overall Score and SF-12 Physical Score (estimate = 0.05 ± 0.01, p < 0.001 and estimate = 0.05 ± 0.02, p = 0.012, respectively). SPPB was a significant, weak predictor of KCCQ Physical Score and SF-12 Physical Score (estimate = 1.37 ± 0.66, p = 0.040 and estimate = 0.54 ± 0.25, p = 0.030, respectively). CONCLUSION: In older, hospitalized ADHF patients, PF and QOL are both severely impaired but are only modestly related, suggesting that PF and QOL provide complementary information and assessment of both should be considered to fully assess clinically meaningful patient-oriented outcomes.

Comparison of the Relation of Carotid Intima-Media Thickness With Incident Heart Failure With Reduced Versus Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Increased carotid intima-media thickness (cIMT) is associated with heart failure (HF) in previous studies, but it is not known whether the association of cIMT differs between HF with reduced (HFrEF) versus preserved ejection fraction (HFpEF). We studied 6699 participants (mean age 62 ± 10 years, 47% male, and 38% white) from the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline cIMT measurements. We classified HF events as HFrEF (EF <50%) or HFpEF (EF ≥ 50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios (HR), and 95% confidence intervals (CI) for the association between the IMT Z-score (measured maximum IMT of Internal Carotid (IC) and Common Carotid (CC) sites as the mean of the maximum IMT of the near and far walls of right and left sides), and incident HFrEF or HFpEF. Models were adjusted for covariates and interim coronary artery disease (CAD) events. A total of 191 HFrEF and 167 HFpEF events occurred during follow-up. In multivariable analysis, each 1 standard deviation increase in the measured maximum IMT (Z-score) was associated with both HFrEF and HFpEF in the unadjusted and demographically adjusted models [HR, 95% CI 1.57 (1.43 to 1.73)] and [HR, 95% CI 1.61 (1.47 to 1.77)] but not in the fully adjusted models [HR, 95% CI 1.11 (0.96 to 1.28)] and [HR, 95% CI 1.13 (0.98 to 1.30)]. In conclusion, cIMT was significantly associated with incident HF, but the association is partially attenuated with adjustment for demographic factors and becomes non-significant after adjustment for other traditional heart failure risk factors and interim CAD events. There was no difference in the association of IMT measures with HFrEF versus HFpEF.

Alcohol consumption and subclinical atherosclerosis among South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.

BACKGROUND: South Asians are the second fastest growing ethnic group in the United States, and they have a high risk for cardiovascular disease (CVD). Moderate alcohol consumption has been associated with lower CVD risk in some race/ethnic groups, but the association of alcohol consumption and atherosclerosis in South Asians has not been investigated. METHODS AND RESULTS: We used data from 906 South Asian participants who participated in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort (2010-2012). Alcohol consumption was ascertained via questionnaire, coronary artery calcium (CAC) was measured with computed tomography, and common carotid artery intima-media thickness (cIMT) was measured using B-mode ultrasonography. We used multivariable regression models to examine cross-sectional associations of alcohol consumption with the presence and amount of CAC and cIMT. Compared with never drinkers, participants consuming 4-7 drinks/week had a 63% decreased odds of any CAC after adjusting for potential confounders and mediators. Participants consuming 4-7 drinks/week had significantly lower odds of CAC score between 1 and 300 [OR (95% CI): 0.34 (0.16-0.72)]. A similar inverse association was seen for the odds of CAC>300 [OR (95% CI): 0.28 (0.07-0.97)]. Alcohol consumption of >7 drinks/week was associated with a 0.096 mm increase in common-cIMT. CONCLUSION: There was an inverse association between the amount of alcohol intake and CAC among South Asians while a positive association was found between alcohol consumption and common-cIMT. Long-term follow-up of the MASALA cohort will examine prospective associations of alcohol intake with the progression of subclinical atherosclerosis, incident CVD events, and mortality.

Relation of Elevated Resting Heart Rate in Mid-Life to Cognitive Decline Over 20 Years (from the Atherosclerosis Risk in Communities [ARIC] Study).

Resting heart rate (RHR) is independently associated with cardiovascular disease (CVD) risk. We determined whether RHR, measured in mid-life, is also associated with cognitive decline. We studied 13,720 middle-aged white and black ARIC participants without a history of stroke or atrial fibrillation. RHR was obtained from a 12-lead resting electrocardiogram at the baseline visit (1990 to 1992) and categorized into groups as <60 (reference), 60 to 69, 70 to 79 and ≥80 beats/min. Cognitive scores were obtained at baseline and at up to 2 additional visits (1996 to 1998 and 2011 to 2013). The primary outcome was a global composite cognitive score (Z-score) derived from 3 tests: delayed word recall, digit symbol substitution, and word fluency. The associations of RHR with cognitive decline and incident dementia were examined using linear mixed-effects and Cox hazard models, respectively, adjusting for sociodemographics, CVD risk factors, and AV-nodal blockade use. Multiple imputation methods were used to account for attrition over follow-up. Participants had mean ± SD age of 58 ± 6 years; 56% were women, 24% black. Average RHR was 66 ± 10 beats/min. Over a mean follow-up of 20 years, those with RHR ≥80 beats/min had greater global cognitive decline (average adjusted Z-score difference -0.12 [95% confidence interval -0.21, -0.03]) and increased risk for incident dementia (hazard ratio 1.28 (1.04, 1.57), compared with those with RHR <60 beats/min. In conclusion, elevated RHR is independently associated with greater cognitive decline and incident dementia over 20 years. Further studies are needed to determine whether the associations are causal or secondary to another underlying process, and whether modification of RHR can affect cognitive decline.

Relation of Coronary Artery Calcium and Extra-Coronary Aortic Calcium to Incident Hypertension (from the Multi-Ethnic Study of Atherosclerosis).

Arterial calcification reflects an atherosclerotic process associated with vascular stiffness. Whether baseline coronary artery calcium (CAC) and extra-coronary calcium (ECC), measured using noncontrast computed tomography imaging, are associated with incident hypertension is poorly understood. We studied participants from the Multi-Ethnic Study of Atherosclerosis without measured or self-reported hypertension at baseline. Incident hypertension was defined by blood pressure criteria (BP, ≥140/90 mmHg), BP medication use, or both, and was assessed at in-person visits. We analyzed incident hypertension using multivariable-adjusted discrete-time proportional hazards models. Net reclassification improvement (NRI) assessed whether CAC reclassified hypertension risk when added to the Framingham hypertension risk score. Among 3,304 subjects analyzed, mean age was 59 ± 10 years; 48% were male and 42% were white. There were 1,283 incident hypertension cases over a median (interquartile range) follow-up time of 10.6 (4.5, 11.5) years. Each 1-unit increase in ln(CAC+1) was independently associated with a 12% higher risk of hypertension (95% confidence interval [CI] 9% to 16%). Relative to CAC = 0, patients with CAC >400 had a hazard ratio for incident hypertension of 2.2 (95% CI 1.8 to 2.9). There was no interaction by age, gender, or baseline BP (p = 0.43, 0.19, 0.09, respectively). Continuous NRI analyses demonstrated that CAC can reclassify risk of incident hypertension; NRI = 0.19 (95% CI 0.10 to 0.26). Furthermore, all measurements of ECC were significantly associated with incident hypertension, even after adjustment for CAC (hazard ratios ranging from 1.36 to 1.38). In conclusion, patients with CAC and ECC are at markedly higher risk of incident hypertension and may benefit from more intensified prevention efforts.

Electrocardiographic subclinical myocardial injury and alcohol consumption: a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Cardiac Infarction/Injury Score (CIIS), an electrocardiographic based scoring system, is a surrogate marker of subclinical myocardial injury (SC-MI) and has shown excellent prognostic value in predicting future cardiovascular mortality. As an association of mild to moderate alcohol consumption with cardiovascular disease (CVD) is conflicting, using an electrocardiographic based scoring system such as CIIS is a simple and cost-effective way to investigate this controversial relationship. METHODS: This analysis included 6090 participants (58.42±13.12 years, 54.2% women) free of CVD from the Third National Health and Nutrition Examination Survey (NHANES III). We used multivariable linear regression analysis to examine the cross-sectional association between each alcohol category (non-drinker (reference), 1-6 drinks/week, 7-13 drinks/week, ≥14 drinks/week, and CIIS. SC-MI was defined as CIIS ≥10 units. RESULTS: The prevalence of SC-MI was high among heavy drinkers (≥14 drinks/week) and was lower in participants who were moderate drinkers (7-13 drinks/week). There was a statistically significant and inverse association between moderate alcohol consumption and CIIS (ß (95% CI): -0.64 (-1.27, -0.007), P = 0.04) using multivariable linear regression analysis. This inverse association between moderate alcohol consumption and CIIS was more striking among whites compared to non-whites (ß (95% CI): -1.06 (-1.93, -0.19) vs. 0.05 (-0.91, 1.00) respectively; interaction p-value = 0.08). Also, the association was stronger among women and older participants, however interaction p-value did not reach statistical significance. CONCLUSION: There is an inverse association between moderate alcohol consumption and CIIS in participants without manifestations of CVD. As lower CIIS has been associated with low risk of poor outcomes including CVD mortality, these findings further support the existing evidence of the potential benefits of moderate alcohol consumption on cardiovascular health.

Relation of Resting Heart Rate to Incident Atrial Fibrillation (from the Henry Ford Hospital Exercise Testing Project).

Autonomic nervous system (ANS) dysfunction plays a role in atrial fibrillation (AF) initiation. Cardiorespiratory fitness modulates ANS function and is inversely associated with resting heart rate (RHR) and risk of AF. Thus, we sought to study the association between RHR, as a surrogate for ANS function, and incident AF independent of exercise capacity (EC). We analyzed 51,436 subjects without previous AF who underwent a clinically indicated exercise stress test. Incident AF was ascertained through claims files. RHR was measured before stress testing, and EC was estimated by peak metabolic equivalents of task. We studied the association between RHR categories (<70, 70 to 85 [reference], and >85 beats/min) and incident AF using Cox models adjusted for risk factors and for EC. We tested for interaction between RHR and age, gender, smoking, and EC. Mean (SD) age was 53 (13) years, 53% were men, and 28% were black. Participants with RHR <70 beats/min were older, more likely to be men, have higher EC, and more likely to smoke but less likely to have diabetes and hypertension. Over a median of 5.5 years, RHR <70 beats/min was associated with 14% increased risk of AF (95 CI 6% to 25%) in fully adjusted models, whereas RHR >85 beats/min was not associated with AF risk after adjusting for EC. Results for RHR analyzed continuously and by quartile were similar. No interaction was seen. In conclusion, subjects with low RHR at all levels of EC are at increased risk of AF and may benefit from heart rhythm surveillance, particularly in the presence of other AF risk factors.

The Association of Resting Heart Rate and Incident Hypertension: The Henry Ford Hospital Exercise Testing (FIT) Project.

BACKGROUND: Given that sympathetic tone is associated with hypertension, we sought to determine whether resting heart rate (RHR), as a surrogate for cardiac autonomic function, was associated with incident hypertension. METHODS: We analyzed 21,873 individuals without a history of hypertension who underwent a clinically indicated exercise stress test. Baseline RHR was assessed prior to testing and was categorized as <70, 70-85, and >85 beats-per-minute (bpm). Incident hypertension was defined by subsequent diagnosis codes for new-onset hypertension from three or more encounters. We tested for effect modification by age (<60 vs. ≥60 years), sex, race, and history of coronary heart disease (CHD). RESULTS: Mean (±SD) age was 49 (±12) years, 55% were men and 21% were Black. Compared to the lowest RHR (<70 bpm) category, patients in the highest category (>85 bpm) were younger, more likely to be female, heavier, diabetic, and achieve lower metabolic equivalents (METS). Over a median of 4 years follow-up, there were 8,179 cases of incident hypertension. Compared to RHR <70 bpm, persons with RHR >85 bpm had increased risk of hypertension after adjustment for CHD risk factors, baseline blood pressure (BP), and METS (hazard ratio = 1.15 (95% confidence interval 1.08-1.23)). Age was an effect modifier (interaction P = 0.02), whereas sex, race, and CHD were not. In age-stratified analyses the relationship remained significant only in those younger than 60 years. CONCLUSION: Elevated RHR is an independent risk factor for incident hypertension, particularly in younger persons. Whether lifestyle modification or other strategies to reduce RHR can prevent incident hypertension in high-risk individuals warrants further study.

Relation of resting heart rate to risk for all-cause mortality by gender after considering exercise capacity (the Henry Ford exercise testing project).

Whether resting heart rate (RHR) predicts mortality independent of fitness is not well established, particularly among women. We analyzed data from 56,634 subjects (49% women) without known coronary artery disease or atrial fibrillation who underwent a clinically indicated exercise stress test. Baseline RHR was divided into 5 groups with <60 beats/min as reference. The Social Security Death Index was used to ascertain vital status. Cox hazard models were performed to determine the association of RHR with all-cause mortality, major adverse cardiovascular events, myocardial infarction, or revascularization after sequential adjustment for demographics, cardiovascular disease risk factors, medications, and fitness (metabolic equivalents). The mean age was 53 ± 12 years and mean RHR was 73 ± 12 beats/min. More than half of the participants were referred for chest pain; 81% completed an adequate stress test and mean metabolic equivalents achieved was 9.2 ± 3. There were 6,255 deaths over 11.0-year mean follow-up. There was an increased risk of all-cause mortality with increasing RHR (p trend <0.001). Compared with the lowest RHR group, participants with an RHR ≥90 beats/min had a significantly increased risk of mortality even after adjustment for fitness (hazard ratio 1.22, 95% confidence interval 1.10 to 1.35). This relationship remained significant for men, but not significant for women after adjustment for fitness (p interaction <0.001). No significant associations were seen for men or women with major adverse cardiovascular events, myocardial infarction, or revascularization after accounting for fitness. In conclusion, after adjustment for fitness, elevated RHR was an independent risk factor for all-cause mortality in men but not women, suggesting gender differences in the utility of RHR for risk stratification.