Waqas T. Qureshi

Cardiorespiratory Fitness and Risk of Incident Atrial Fibrillation Results From the Henry Ford Exercise Testing (FIT) Project

Background— Poor cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between CRF and atrial fibrillation (AF) is less clear. The aim of this analysis was to investigate the association between CRF and incident AF in a large, multiracial cohort that underwent graded exercise treadmill testing. Methods and Results— From 1991 to 2009, a total of 64 561 adults (mean age, 54.5±12.7 years; 46% female; 64% white) without AF underwent exercise treadmill testing at a tertiary care center. Baseline demographic and clinical variables were collected. Incident AF was ascertained by use of International Classification of Diseases, Ninth Revision code 427.31 and confirmed by linkage to medical claim files. Nested, multivariable Cox proportional hazards models were used to estimate the independent association of CRF with incident AF. During a median follow-up of 5.4 years (interquartile range, 3–9 years), 4616 new cases of AF were diagnosed. After adjustment for potential confounders, 1 higher metabolic equivalent achieved during treadmill testing was associated with a 7% lower risk of incident AF (hazard ratio, 0.93; 95% confidence interval, 0.92–0.94; P<0.001). This relationship remained significant after adjustment for incident coronary artery disease (hazard ratio, 0.92; 95% confidence interval, 0.91–0.93; P<0.001). The magnitude of the inverse association between CRF and incident AF was greater among obese compared with nonobese individuals (P for interaction=0.02). Conclusions— There is a graded, inverse relationship between cardiorespiratory fitness and incident AF, especially among obese patients. Future studies should examine whether changes in fitness increase or decrease risk of atrial fibrillation. This association was stronger for obese compared with nonobese, especially among obese patients.

Cardiorespiratory Fitness and Incident Diabetes: The FIT (Henry Ford Exercise Testing) Project

OBJECTIVE Prior evidence has linked higher cardiorespiratory fitness with a lower risk of diabetes in ambulatory populations. Using a demographically diverse study sample, we examined the association of fitness with incident diabetes in 46,979 patients from The Henry Ford ExercIse Testing (FIT) Project without diabetes at baseline. RESEARCH DESIGN AND METHODS Fitness was measured during a clinician-referred treadmill stress test performed between 1991 and 2009. Incident diabetes was defined as a new diagnosis of diabetes on three separate consecutive encounters derived from electronic medical records or administrative claims files. Analyses were performed with Cox proportional hazards models and were adjusted for diabetes risk factors. RESULTS The mean age was 53 years with 48% women and 27% black patients. Mean metabolic equivalents (METs) achieved was 9.5 (SD 3.0). During a median follow-up period of 5.2 years (interquartile range 2.6–8.3 years), there were 6,851 new diabetes cases (14.6%). After adjustment, patients achieving ≥12 METs had a 54% lower risk of incident diabetes compared with patients achieving <6 METs (hazard ratio 0.46 [95% CI 0.41, 0.51]; P-trend < 0.001). This relationship was preserved across strata of age, sex, race, obesity, hypertension, and hyperlipidemia. CONCLUSIONS These data demonstrate that higher fitness is associated with a lower risk of incident diabetes regardless of demographic characteristics and baseline risk factors. Future studies should examine the association between change in fitness over time and incident diabetes.

Omega-6 fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

BACKGROUND The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. METHODS We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. FINDINGS Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). INTERPRETATION Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. FUNDING Funders are shown in the appendix.

Relation Between Cancer and Atrial Fibrillation (from the REasons for Geographic And Racial Differences in Stroke Study)

Atrial fibrillation (AF) is common in patients with life-threatening cancer and those undergoing active cancer treatment. However, data from subjects with a history of non-life-threatening cancer and those who do not require active cancer treatment are lacking. A total of 15,428 (mean age 66 ± 8.9 years; 47% women; 45% blacks) participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study with baseline data on previous cancer diagnosis and AF were included. Participants with life-threatening cancer and active cancer treatment within 2 years of study enrollment were excluded. History of cancer was identified using computer-assisted telephone interviews. AF cases were identified from baseline electrocardiogram data and by a self-reported history of a previous diagnosis. Logistic regression was used to examine the cross-sectional association between cancer diagnosis and AF. A total of 2,248 (15%) participants had a diagnosis of cancer and 1,295 (8.4%) had AF. In a multivariable logistic regression model adjusted for sociodemographic characteristics (age, gender, race, education, income, and region of residence) and cardiovascular risk factors (systolic blood pressure, high-density lipoprotein cholesterol, total cholesterol, C-reactive protein, body mass index, smoking, diabetes, antihypertensive and lipid-lowering agents, left ventricular hypertrophy, and cardiovascular disease), those with cancer were more likely to have prevalent AF than those without cancer (odds ratio 1.19, 95% confidence interval 1.02 to 1.38). Subgroup analyses by age, sex, race, cardiovascular disease, and C-reactive protein yielded similar results. In conclusion, AF was more prevalent in participants with a history of non-life-threatening cancer and those who did not require active cancer treatment in REGARDS.

Implications of the new American College of Cardiology/American Heart Association cholesterol guidelines for primary atherosclerotic cardiovascular disease event prevention in a multi ethnic cohort: Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND The impact of replacing the National Cholesterol Education Program (NCEP)/Adult Treatment Program (ATP) III cholesterol guidelines with the new 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for primary prevention of cardiovascular disease is unclear. METHODS We used risk factor and 10-year clinical event rate data from MESA, combined with estimates of efficacy of moderate and high-intensity statin therapy from meta-analyses of statin primary prevention trials to estimate (a) the change in number of subjects eligible for drug therapy and (2) the anticipated reduction in atherosclerotic cardiovascular disease (ASCVD) events and increment in type 2 diabetes mellitus (T2DM) associated with the change in cholesterol guidelines. RESULTS Of the 6,814 MESA participants, 5,437 were not on statins at baseline and had complete data for analysis (mean age 61.4±10.3). Using the NCEP/ATP III guidelines, 1,334 (24.5%) would have been eligible for statin therapy compared with 3,015 (55.5%) under the new ACC/AHA guidelines. Among the subset of newly eligible, 127/1,742 (7.3%) had an ASCVD event during 10years of follow-up. Assuming 10years of moderate-intensity statin therapy, the estimated absolute reduction in ASCVD events for the newly eligible group was 2.06% (number needed to treat [NNT] 48.6) and the estimated absolute increase in T2DM was 0.90% (number needed to harm [NNH] 110.7). Assuming 10years of high-intensity statin therapy, the corresponding estimates for reductions in ASCVD and increases in T2DM were as follows: ASCVD 2.70% (NNT 37.5) and T2DM 2.60% (NNH 38.6). The estimated effects of moderate-intensity statins on 10-year risk for ASCVD and T2DM in participants eligible for statins under the NCEP/ATP III were as follows: 3.20% (NNT 31.5) and 1.06% (NNH 94.2), respectively. CONCLUSION Substituting the NCEP/ATP III cholesterol guidelines with the 2013 ACC/AHA cholesterol guidelines in MESA more than doubled the number of participants eligible for statin therapy. If the new ACC/AHA cholesterol guidelines are adopted and extend the primary prevention population eligible for treatment, the risk-benefit profile is much better for moderate-intensity than high-intensity statin treatment.

Implications of the new American College of Cardiology/American Heart Association cholesterol guidelines for primary atherosclerotic cardiovascular disease event prevention in a multi ethnic cohort

BACKGROUND The impact of replacing the National Cholesterol Education Program (NCEP)/Adult Treatment Program (ATP) III cholesterol guidelines with the new 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for primary prevention of cardiovascular disease is unclear. METHODS We used risk factor and 10-year clinical event rate data from MESA, combined with estimates of efficacy of moderate and high-intensity statin therapy from meta-analyses of statin primary prevention trials to estimate (a) the change in number of subjects eligible for drug therapy and (2) the anticipated reduction in atherosclerotic cardiovascular disease (ASCVD) events and increment in type 2 diabetes mellitus (T2DM) associated with the change in cholesterol guidelines. RESULTS Of the 6,814 MESA participants, 5,437 were not on statins at baseline and had complete data for analysis (mean age 61.4±10.3). Using the NCEP/ATP III guidelines, 1,334 (24.5%) would have been eligible for statin therapy compared with 3,015 (55.5%) under the new ACC/AHA guidelines. Among the subset of newly eligible, 127/1,742 (7.3%) had an ASCVD event during 10years of follow-up. Assuming 10years of moderate-intensity statin therapy, the estimated absolute reduction in ASCVD events for the newly eligible group was 2.06% (number needed to treat [NNT] 48.6) and the estimated absolute increase in T2DM was 0.90% (number needed to harm [NNH] 110.7). Assuming 10years of high-intensity statin therapy, the corresponding estimates for reductions in ASCVD and increases in T2DM were as follows: ASCVD 2.70% (NNT 37.5) and T2DM 2.60% (NNH 38.6). The estimated effects of moderate-intensity statins on 10-year risk for ASCVD and T2DM in participants eligible for statins under the NCEP/ATP III were as follows: 3.20% (NNT 31.5) and 1.06% (NNH 94.2), respectively. CONCLUSION Substituting the NCEP/ATP III cholesterol guidelines with the 2013 ACC/AHA cholesterol guidelines in MESA more than doubled the number of participants eligible for statin therapy. If the new ACC/AHA cholesterol guidelines are adopted and extend the primary prevention population eligible for treatment, the risk-benefit profile is much better for moderate-intensity than high-intensity statin treatment.

Electrocardiographic and Echocardiographic Left Ventricular Hypertrophy in the Prediction of Stroke in the Elderly.

INTRODUCTION It is unclear whether left ventricular hypertrophy (LVH) detected by electrocardiography (ECG-LVH) is equally predictive of heart failure as LVH detected by echocardiography (echo-LVH). METHODS This analysis included 4,008 white participants (41% men) aged 65 years or older from the Cardiovascular Health Study who were free of stroke and major intraventricular conduction defects. ECG-LVH was defined by the Cornell criteria from baseline ECG data and echo-LVH was calculated from baseline echocardiography measurements. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ECG-LVH and echo-LVH and adjudicated incident stroke events, separately. Harrells concordance indices (C-index) were calculated for the Framingham Stroke Risk Score with inclusion of ECG-LVH and echo-LVH, separately. RESULTS ECG-LVH was detected in 136 (3.4%) participants and echo-LVH was present in 208 (5.2%) participants. Over a median follow-up of 13 years, a total of 769 (19%; incidence rate = 15.4 per 1000 person-years) strokes occurred. In a multivariable Cox regression analysis adjusted for stroke risk factors and potential confounders, ECG-LVH (HR = 1.68; 95% CI = 1.23, 2.28) and echo-LVH (HR = 1.58; 95% CI = 1.17, 2.14) were associated with an increased risk of stroke. Similar values were obtained for the C-index when either ECG-LVH (C-index = .786) or echo-LVH (C-index = .786) were included in the Framingham Stroke Risk Score. CONCLUSION ECG-LVH and echo-LVH are able to be used interchangeably in stroke risk scores.

Sex Differences in Cardiorespiratory Fitness and All-Cause Mortality: The Henry Ford ExercIse Testing (FIT) Project

OBJECTIVE To determine whether sex modifies the relationship between fitness and mortality. PATIENTS AND METHODS We included 57,284 patients without coronary artery disease or heart failure who completed a routine treadmill exercise test between 1991 and 2009. We determined metabolic equivalent tasks (METs) and linked patient records with mortality data via the Social Security Death Index. Multivariable Cox regression was used to determine the association between sex, fitness, and all-cause mortality. RESULTS There were 29,470 men (51.4%) and 27,814 women (48.6%) with mean ages of 53 and 54 years, respectively. Overall, men achieved 1.7 METs higher than women (P<.001). During median follow-up of 10 years, there were 6402 deaths. The mortality rate for men in each MET group was similar to that for women, who achieved an average of 2.6 METs lower (P=.004). Fitness was inversely associated with mortality in both men (hazard ratio [HR], 0.84 per 1 MET; 95% CI, 0.83-0.85) and women (HR, 0.83 per 1 MET; 95% CI, 0.81-0.84). This relationship did not plateau at high or low MET values. CONCLUSION Although men demonstrated 1.7 METs higher than women, their survival was equivalent to that of women demonstrating 2.6 METs lower. Furthermore, higher MET values were associated with lower mortality for both men and women across the range of MET values. These findings are useful for tailoring prognostic information and lifestyle guidance to men and women undergoing stress testing.

Electrocardiographic Versus Echocardiographic Left Ventricular Hypertrophy in Prediction of Congestive Heart Failure in the Elderly.

Left ventricular hypertrophy (LVH) is an established risk factor for heart failure (HF) and is a component of the Framingham Heart Failure Risk Score (FHFRS). Whether LVH detected by electrocardiogram (ECG‐LVH) is equally predictive of HF as LVH detected by echocardiography (echo‐LVH) is unclear.

Sustained pre-hypertensive blood pressure and incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis

The association between sustained pre-hypertension and atrial fibrillation (AF) has not been thoroughly examined. This study included 5311 participants (mean age 62 ± 10 years; 47% male; 42.9% non-whites) from the Multi-Ethnic Study of Atherosclerosis. Sustained exposure was based on 2 or more visits within the same blood pressure category (optimal, <120/80 mm Hg; pre-hypertension, 120-139/80-89 mm Hg; hypertension, ≥140/90 mm Hg or antihypertensive medication use) during visits 1, 2, and 3. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between blood pressure category and AF. Over a median follow-up of 5.3 years, 182 (3.4%) participants developed AF. Pre-hypertension and hypertension were associated with an increased risk of AF compared with participants who had optimal blood pressure (optimal: HR, 1.0; referent; pre-hypertension: HR, 1.8; 95% CI, 1.004-3.2; hypertension: HR, 2.6; 95% CI, 1.6-4.4). Sustained pre-hypertension is associated with an increased risk of AF.