Assessing Glycosylated Hemoglobin Thresholds for Development of Cardiovascular Disease by Racial and Ethnic Groups.

BACKGROUND: Diabetes is the strongest risk factor for cardiovascular disease, and although glycosylated hemoglobin (HbA1c) levels are known to vary by race, no racial and ethnic-specific diagnostic thresholds exist for diabetes in prediction of cardiovascular disease events. The purpose of this study is to determine whether HbA1c thresholds for predicting major adverse cardiovascular events (MACEs) differ among racial and ethnic groups. METHODS AND RESULTS: This is a retrospective cohort study of Kaiser Permanente Northern California adult members (n=309 636) with no history of cardiovascular disease who had HbA1c values and race and ethnicity data available between 2014 and 2019. Multivariable logistic regression was used to evaluate the odds of MACEs by the following racial and ethnic groups: Filipino, South Asian, East Asian, Black, White, and Hispanic. A Youden index was used to calculate HbA1c thresholds for MACE prediction by each racial and ethnic group, stratified by sex. Among studied racial and ethnic groups, South Asian race was associated with the greatest odds of MACEs (1.641 [95% CI, 1.456-1.843]; P<0.0001). HbA1c was a positive predictor for MACEs, with an odds ratio of 1.024 (95% CI, 1.022-1.025) for each 0.1% increment increase in HbA1c. HbA1c values varied between 6.0% and 7.6% in MACE prediction by race and ethnicity and sex. White individuals, South Asian individuals, East Asian women, and Black men had HbA1c thresholds for MACE prediction in the prediabetic range, between 6.0% and 6.2%. Black women, Hispanic men, and East Asian men had HbA1c thresholds of 6.2% to 6.6%, less than the typical threshold of 7.0% that is used as a treatment goal. CONCLUSIONS: Findings suggest that the use of race and ethnic- and sex-specific HbA1c thresholds may need to be considered in treatment goals and cardiovascular disease risk estimation.

Heart health for South Asians: improved cardiovascular risk factors with a culturally tailored health education program.

BACKGROUND/AIM: The Kaiser Permanente (KP) Northern California Heart Health for South Asians (HHSA) Program is a two-hour educational class that provides culturally relevant lifestyle and dietary recommendations to South Asian (SA) patients, in an effort to reduce their known disproportionate burden of cardiovascular (CV) disease. We evaluated the impact of the HHSA Program on CV risk factors and major adverse CV events (MACE). METHODS: A retrospective cohort study identified 1517 participants of SA descent, ≥ 18 years old from 2006 to 2019. We evaluated the change in risk factors with program attendance (median follow up of 6.9 years) for systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), LDL, HDL, BMI, and HbA1c. We also performed a propensity matched analysis to evaluate differences in MACE including stroke, myocardial infarction (MI), coronary revascularization, and all-cause mortality. RESULTS: There were significant improvements in DBP, TG, LDL-c, HDL-c, BMI, and HbA1c at one year follow up and sustained improvements in DBP (-1.01mmHg, p = 0.01), TG (-13.74 mg/dL, p = 0.0001), LDL-c (-8.43 mg/dL, p = < 0.0001), and HDL-c (3.16 mg/dL, p = < 0.0001) levels at the end of follow up. In the propensity matched analysis, there was a significant reduction in revascularization (OR 0.33, 95% CI 0.14-0.78, p = 0.011) and mortality (OR 0.41, 95% CI 0.22-0.79, p = 0.008), and a trend towards reduction in stroke. CONCLUSIONS: Our study demonstrates the efficacy of a culturally tailored SA health education program in improving CV risk factors and reducing MACE. The program highlights the importance and value of providing culturally tailored health education in primary CV disease prevention.

Performance of the pooled cohort equation in South Asians: insights from a large integrated healthcare delivery system.

South Asian ethnicity is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk and has been identified as a "risk enhancer" in the 2018 American College of Cardiology/American Heart Association Guidelines. Risk estimation and statin eligibility in South Asians is not well understood; we studied the accuracy of 10-years ASCVD risk prediction by the pooled cohort equation (PCE), based on statin use, in a South Asian cohort. This is a retrospective cohort study of Kaiser Permanente Northern California South Asian members without existing ASCVD, age range 30-70, and 10-years follow up. ASCVD events were defined as myocardial infarction, ischemic stroke, and cardiovascular death. The cohort was stratified by statin use during the study period: never; at baseline and during follow-up; and only during follow-up. Predicted probability of ASCVD, using the PCE was calculated and compared to observed ASCVD events for low < 5.0%, borderline 5.0 to < 7.5%, intermediate 7.5 to < 20.0%, and high ≥ 20.0% risk groups. A total of 1835 South Asian members were included: 773 never on statin, 374 on statins at baseline and follow-up, and 688 on statins during follow-up only. ASCVD risk was underestimated by the PCE in low-risk groups: entire cohort: 1.8 versus 4.9%, p < 0.0001; on statin at baseline and follow-up: 2.58 versus 8.43%, p < 0.0001; on statin during follow-up only: 2.18 versus 7.77%, p < 0.0001; and never on statin: 1.37 versus 2.09%, p = 0.12. In this South Asian cohort, the PCE underestimated risk in South Asians, regardless of statin use, in the low risk ASCVD risk category.

Left ventricular end-systolic volume response post-stress echocardiography: Dilation as a marker of multi-vessel coronary artery disease.

BACKGROUND: Transient ischemic dilation of the left ventricle (LV) during stress echocardiography indicates extensive myocardial ischemia. It remains unclear whether the change of LV end-systolic volume (ESV) or end-diastolic volume (EDV) better correlated with significant coronary artery disease (CAD). Meanwhile, the clinical significance of the extent of the volumetric change post-stress has not been investigated. METHODS: One hundred and five individuals (62 ± 12 years and 75% men) who underwent coronary angiography following exercise treadmill echocardiography were enrolled retrospectively. An additional 30 age- and sex-matched healthy subjects were included for comparison. LV dilation was defined as any increase in LV volume from rest to peak exercise. Patients who had at least two coronary arteries with significant stenosis were considered as having multi-vessel CAD. RESULTS: Thirty-four patients had ESV dilation during exercise echocardiography. On the contrary, ESV decreased at peak exercise in all healthy subjects. Forty-one patients had multi-vessel CAD, and its prevalence was higher in patients with ESV dilation (65% vs 27%, p = 0.001). The extent of ESV increase correlated with CAD severity. ESV dilation is associated with multi-vessel CAD (Odds ratio [OR] 5.02, 95% confidence interval [CI] 2.09 - 12.07, p < 0.001). After adjustment for EDV increase, clinical, electrocardiographic, and echocardiographic variables, the association remained significant (adjusted OR 5.57, 95% CI 1.37-22.64; p = 0.02). CONCLUSIONS: ESV dilation independently correlated with multi-vessel CAD, whereas EDV dilation did not. The amount of ESV increase correlated with the severity of CAD. Our findings provide a rationale for incorporating volume measurements into stress echocardiography practice.

South Asian ethnicity as a risk factor for coronary heart disease.

BACKGROUND AND AIMS: South Asian ethnicity has been associated with increased cardiovascular risk, in the context of a greater burden of traditional cardiovascular disease risk factors. We aimed to identify the 10-year incidence of coronary heart disease (CHD) in South Asians, as compared to other racial-ethnic groups, in a retrospective cohort study, using the Kaiser Permanente Northern California integrated health care system, and to understand whether traditional risk factors could explain differences in outcomes. METHODS AND RESULTS: A study cohort established in 2006, with 10-year follow-up, identified a total n = 341,309 patients, including 5149 South Asians, aged 30-70 years who underwent a screening lipid panel and had no prior history of CHD. There were a total of 460 (8.93%) patients with at least one cardiovascular event, including cardiovascular death, coronary artery revascularization, and myocardial infarction, in South Asians, as compared to 5.66% patients in the total population (p < 0.0001). In a multivariable logistic regression analysis, South Asian ethnicity, compared to White race, was associated with an adjusted odds ratio (aOR) = 2.04 (95%CI: 1.83, 2.28) in predicting the cardiovascular outcomes. CONCLUSIONS: South Asian ethnicity, even after adjustment for traditional risk factors, is associated with an increased risk of coronary heart disease outcomes. This risk was greater than other studied racial-ethnic groups and second only to diabetes in CHD risk prediction.

Image Diagnosis: Takotsubo Cardiomyopathy Mimicking an Acute ST Elevation Myocardial Infarction in the Setting of Anti-Depressant Therapy Withdrawal.

CASE PRESENTATION: A 77-year-old woman with a history of bipolar disorder, hypertension, hyperlipidemia, and previous tobacco use presented to the Emergency Department (ED) with acute shortness of breath and diaphoresis. The patient was initially anxious and tearful upon presentation to the ED. While she denied acute emotional or social stressors, she did note abruptly stopping her venlafaxine (brand name Effexor) approximately 3 weeks before. Results of an initial electrocardiogram (ECG) showed an ectopic atrial rhythm with marked diffuse ST-segment elevation most prominent in the anterolateral leads (Figure 1). Results of bedside echocardiography demonstrated a large territory of hypokinesis involving all apical segments with hypercontractile basal segments (Figure 2). Emergent invasive coronary angiography was performed, which demonstrated no obstructive coronary artery disease. Initial troponin I level was 1.26 ng/mL (normal < 0.04 ng/mL). Results of a subsequent ECG obtained at 4-week follow-up illustrated resolution of previously seen ST elevations, now with anterolateral T-wave inversions (Figure 3). Results of repeat echocardiography at 4-week follow-up demonstrated normalization of left ventricular systolic function and no segmental wall-motion abnormalities.

Who is young at heart and when? Diastolic Doppler data from the mind your heart study.

To further define the age-related distribution of diastolic function as defined by E/A ratio, in healthy male adults. The age-sensitive ratio of mitral inflow E-wave to A-wave (E/A) velocity is often considered in the evaluation of diastolic function. To appropriately direct a comprehensive evaluation of diastolic function, we sought to improve the characterization of the influence of age on E/A ratio. We analyzed echocardiographic data from the Mind Your heart Study, a cohort of outpatients recruited from two San Francisco Veterans centers to examine the effect of mental health on cardiovascular outcomes. Individuals with a history of heart disease or hypertension were excluded, leaving 313 veterans for analysis. We examined E/A by 5-year increments and performed linear and logistic regression analysis to predict trends in E/A and E dominance. Within the age ranges of population (54.9 ± 11.5), there is a steady gradual decline in absolute E/A ratio (beta coefficient/year- 0.018, P < .001) and the odds of E dominance similarly declines with age (odds ratio/year = 0.89, P < .001). Despite this decline, 90% of individuals below the age of 50 years maintain E dominance. Beyond age 50, 55% maintain E dominance, and beyond age 70, only 28% have E dominance. In this adequately healthy population, age-related progression of delayed relaxation appears to be a state of normality rather than diastolic dysfunction. Careful attention to specific cutoff points in age and E/A ratio could avoid misinterpretation or inappropriate management.

The effect of aging on the association between coronary heart disease risk factors and carotid intima media thickness: an analysis of the Atherosclerosis Risk in Communities (ARIC) cohort.

OBJECTIVE: Aging decreases the strength of association between established coronary heart disease (CHD) and its risk factors. Carotid intima media thickness (IMT) is a widely used surrogate for coronary artery disease, which we hypothesized has a similar diminishing age-mediated strength of association with CHD occurrence and prevalence of its risk factors. METHODS AND RESULTS: Data from the Atherosclerosis Risk in Communities (ARIC) cohort of 14,562 individuals aged 45 to 64 (mean follow up nine years) was stratified into two age groups, 45-54 and 55-64 years, within each of ARIC's four examination visits (n=14,562; 13,622; 7869; 6628 for visits 1 to 4, respectively). Cross-sectional and longitudinal analyses with multiple linear and logistic regression modeling were used to compare the relationships between carotid IMT (the mean of six far wall sites from the right and left carotid bifurcation, common and internal carotid arteries with imputation of missing data) and the risk factors of smoking, hypertension, hypercholesterolemia, diabetes, and obesity with age. The strength of the associations between carotid IMT and most risk factors were qualitatively stronger across successive visits and within each visit, these associations were stronger in the older, as compared to the younger, age group. CONCLUSIONS: In a large cohort followed for nearly one decade, our hypothesis that age attenuates the association of CHD risk factors and carotid IMT was not supported by ARIC data. Rather, we found that associations between carotid IMT and CHD risk factors remained stable with advancing age, contrary to the relationship between risk factors and CHD outcomes with age. These findings suggest that there is efficacy to continued risk factor management in the elderly.

Risk factors for and outcomes of detention of patients with TB in New York City: an update: 2002-2009.

BACKGROUND: One of the most controversial aspects of New York City's highly effective TB control program is the use of public health law and court-ordered detention to treat persistently recalcitrant patients with active TB. We now report on characteristics and outcomes of patients undergoing detention for completion of TB treatment due to nonadherence in New York City from 2002 through 2009. METHODS: A retrospective cohort study was designed to compare patients undergoing court-ordered detention (n = 79) and time-matched control subjects undergoing TB treatment in outpatient directly observed therapy (DOT) at Bellevue Hospital in New York City. RESULTS: From January 1, 2002, through December 31, 2009, 79 patients underwent court-ordered detention for TB treatment. Compared with patients completing treatment in DOT, univariate analysis found that detainees were younger; more likely to be of minority race/ethnicity; to have a history of substance abuse, tobacco use, homelessness, incarceration, HIV infection; and to be born in the United States. Multivariate analysis adjusting for other variables found smear positivity (OR = 3.93; 95% CI, 1.05-14.75; P = .04), mental illness (OR = 5.80; 95% CI, 1.18-28.51; P = .03), and substance abuse (OR = 9.25; 95% CI, 2.81-30.39; P < .01) to be the strongest independent predictors of likelihood of detention. Of those initially detained, 46 (58%) completed treatment during inpatient detention, 29(37%) completed treatment under outpatient court-ordered DOT, and four died during their hospitalization. CONCLUSIONS: The majority of patients undergoing court-ordered detention for TB treatment (95%) successfully completed therapy. Likelihood of detention was most strongly associated with factors expected to be associated with poor adherence, including mental illness and substance abuse.

Percutaneous coronary intervention versus optimal medical therapy for prevention of spontaneous myocardial infarction in subjects with stable ischemic heart disease.

BACKGROUND: Contemporary studies have shown that spontaneous but not procedural myocardial infarction (MI) is related to subsequent mortality. Whether percutaneous coronary intervention (PCI) reduces spontaneous (nonprocedural) MI is unknown. METHODS AND RESULTS: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials until October 2012 comparing PCI with optimal medical therapy (OMT) for stable ischemic heart disease and reporting MI outcomes: spontaneous nonprocedural MI, procedural MI, and all MI, including procedure-related MI. Given the varying length of follow-up between trials, a mixed-effect Poisson regression meta-analysis was used. From 12 randomized clinical trials with 37 548 patient-years of follow-up, PCI compared with OMT alone was associated with a significantly lower incident rate ratio (IRR) for spontaneous nonprocedural MI (IRR=0.76; 95% confidence interval [CI], 0.58-0.99) at the risk of a higher rate of procedural MI (IRR=4.11; 95% CI, 2.53-6.88) without any difference in the risk of all MI (IRR=0.96; 95% CI, 0.74-1.21). The point estimate for PCI versus OMT for all-cause mortality (IRR=0.88; 95% CI, 0.75-1.03) and cardiovascular mortality (IRR=0.70; 95% CI, 0.44-1.09) paralleled that for spontaneous nonprocedural MI (but not procedural or all nonfatal MI), although these were not statistically significant. CONCLUSIONS: PCI compared with OMT reduced spontaneous MI at the risk of procedural MI without any difference in all MI. Consistent with prior studies showing that spontaneous MI but not procedural MI is related to subsequent mortality, in the present report the point estimate for reduced mortality with PCI compared with OMT paralleled the prevention of spontaneous MI with PCI. Further studies are needed to determine whether these associations are causal.

Percutaneous coronary intervention versus optimal medical therapy in stable coronary artery disease: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The role of percutaneous coronary intervention (PCI) in the management of stable coronary artery disease remains controversial. Given advancements in medical therapies and stent technology over the last decade, we sought to evaluate whether PCI, when added to medical therapy, improves outcomes when compared with medical therapy alone. METHODS AND RESULTS: We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and CENTRAL databases, until January 2012, for randomized clinical trials comparing revascularization with PCI to optimal medical therapy (OMT) in patients with stable coronary artery disease. The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular death, nonfatal myocardial infarction, subsequent revascularization, and freedom from angina. Primary analyses were based on longest available follow-up with secondary analyses stratified by trial duration, with short-term (≤1 year), intermediate (1-5 years), and long-term (≥5 years) time points. We identified 12 randomized clinical trials enrolling 7182 participants who fulfilled our inclusion criteria. For the primary analyses, when compared with OMT, PCI was associated with no significant improvement in mortality (risk ratio [RR], 0.85; 95% CI, 0.71-1.01), cardiac death (RR, 0.71; 95% CI, 0.47-1.06), nonfatal myocardial infarction (RR, 0.93; 95% CI, 0.70-1.24), or repeat revascularization (RR, 0.93; 95% CI, 0.76-1.14), with consistent results over all follow-up time points. Sensitivity analysis restricted to studies in which there was >50% stent use showed attenuation in the effect size for all-cause mortality (RR, 0.93; 95% CI, 0.78-1.11) with PCI. However, for freedom from angina, there was a significant improved outcome with PCI, as compared with the OMT group (RR, 1.20; 95% CI, 1.06-1.37), evident at all of the follow-up time points. CONCLUSIONS: In this most rigorous and comprehensive analysis in patients with stable coronary artery disease, PCI, as compared with OMT, did not reduce the risk of mortality, cardiovascular death, nonfatal myocardial infarction, or revascularization. PCI, however, provided a greater angina relief compared with OMT alone, larger studies with sufficient power are required to prove this conclusively.

Reactive nitrogen species contribute to innate host defense against Campylobacter jejuni.

Campylobacter jejuni, a gram-negative, invasive organism, is a common cause of food-borne bacterial diarrheal disease. However, the relationship between C. jejuni and the innate immune system is not well described. To better characterize host defense against C. jejuni, we investigated the ability of nitric oxide/reactive nitrogen species to kill two strains of C. jejuni. C. jejuni viability was measured after exposure to reactive nitrogen species produced biochemically as acidified nitrite and by bone marrow-derived macrophages. We report that acidified nitrite caused a 3-log-increased kill of C. jejuni (P < 0.05) at doses that did not affect the viability of Salmonella enterica serovar Typhimurium. Expression of NOS2, the gene responsible for the production of inducible nitric oxide, was increased >100-fold in murine macrophages after incubation with C. jejuni (P < 0.001). These macrophages effected a 2-log-increased kill of C. jejuni over 24 h compared to that by NOS2-/- macrophages unable to produce nitric oxide (P < 0.05). These findings suggest that the mammalian host upregulates the production of nitric oxide in response to exposure to C. jejuni and that nitric oxide and reactive nitrogen species comprise part of the innate defense mechanisms that contribute to the resolution of C. jejuni infection.

Combined use of preoperative methylene blue dye and microcoil localization facilitates thoracoscopic wedge resection of indeterminate pulmonary nodules in children.

The ability to biopsy indeterminate pulmonary lesions in children has evolved with advances in minimal access surgery. Recent advances in preoperative localization including image-guided dye injection or wire implantation have expanded the types of lesions that are accessible via minimal access surgery. We present a case of a 13-year-old boy who underwent preoperative localization using both methylene blue dye and microcoil labeling, and a subsequent thoracoscopic pulmonary wedge resection under the same anesthesia. The combined use of both dye and microcoil localization provides the advantage of superior intraoperative visualization of the lesion and the ability to use fluoroscopy to confirm the presence of the nodule in the surgical specimen. We recommend this technique for the biopsy of indeterminate pulmonary lesions that would not otherwise be accessible via a minimally invasive approach.

Localized persistent interstitial pulmonary emphysema presenting as a spontaneous tension pneumothorax in a full term infant.

Persistent interstitial pulmonary emphysema (PIPE) is a syndrome characterized by air-leakage in the perivascular tissues of the lung, primarily affecting mechanically ventilated neonates. Reports in the literature of infants developing PIPE with no history of respiratory distress syndrome (RDS) or mechanical ventilation are scarce. Here, we present a case of a 3-month-old former full term male infant with no history of RDS or mechanical ventilation who presented with focal cystic lung disease associated with spontaneous tension pneumothorax. He was ultimately found to have PIPE based on pathologic evaluation of the resected cystic region. We believe that focal PIPE should be included in the differential diagnosis of cystic lung disease in a full term, unventilated infant, even when spontaneous pneumothorax is the presenting entity.