Biomedical subjects

J C Evans

Publications and source records attributed to J C Evans.

At least 55 records · Page 3Linked to original sources

PubMed1999

The association of chronic cough with the risk of myocardial infarction: the Framingham Heart Study.

PURPOSE: A persistent inflammatory response accompanying chronic infections may contribute to the risk of coronary atherothrombosis. Recent studies have reported an association between chronic respiratory infections and an increased risk of coronary heart disease; however, these reports have not accounted for important confounders such as impaired lung function. METHODS: We considered chronic cough as an indicator of chronic lung infection or inflammation in the original Framingham Heart Study participants aged 47 to 89 years. Chronic cough was defined as a cough present for at least 3 months in the preceding year and was categorized as either nonproductive or productive. The association of chronic cough with myocardial infarction was examined for six consecutive examination cycles (1965 to 1979) among participants free of myocardial infarction at the baseline examination. In a secondary analysis, plasma fibrinogen levels were measured during examination cycle 10 (1965 to 1967) in a subgroup of the study sample (n = 1,288). Multivariable logistic regression analysis was performed adjusting for age, gender, smoking status, forced vital capacity, and other known risk factors. RESULTS: The cross-sectional pooling method yielded 15,656 person-examinations in 3,637 subjects. During follow-up, there were 291 incident myocardial infarctions. Chronic nonproductive cough (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1 to 2.8) and chronic productive cough (OR 1.6, CI 1.1 to 2.4) were independent predictors of myocardial infarction. Results were unchanged when we further adjusted for a history of heart failure. Adjusted plasma fibrinogen levels (mean +/- SD) were greater in those with chronic nonproductive cough than among those without cough (3.2 +/- 0.6 g/L versus 2.9 +/- 0.6 g/dL, P = 0.001). CONCLUSIONS: These findings provide evidence that chronic cough, a clinical manifestation of pulmonary infection or chronic inflammation, is associated with the risk of myocardial infarction. Acute phase reactants such as plasma fibrinogen may be implicated in this association. Prospective serologic studies of infections as predictors of coronary heart disease risk are warranted.

Aged↗

PubMed1999

Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort.

OBJECTIVES: The purpose of this study was to assess the relative proportions of normal versus impaired left ventricular (LV) systolic function among persons with congestive heart failure (CHF) in the community and to compare their long-term mortality during follow-up. BACKGROUND: Several hospital-based investigations have reported that a high proportion of subjects with CHF have normal LV systolic function. The prevalence and prognosis of CHF with normal LV systolic function in the community are not known. METHODS: We evaluated the echocardiograms of 73 Framingham Heart Study subjects with CHF (33 women, 40 men, mean age 73 years) and 146 age- and gender-matched control subjects (nested case-control study). Impaired LV systolic function was defined as an LV ejection fraction (LVEF) <0.50. RESULTS: Thirty-seven CHF cases (51%) had a normal LVEF; 36 (49%) had a reduced LVEF. Women predominated in the former group (65%), whereas men constituted 75% of the latter group. During a median follow-up of 6.2 years, CHF cases with normal LVEF experienced an annual mortality of 8.7% versus 3.0% for matched control subjects (adjusted hazards ratio = 4.06, 95% confidence interval 1.61 to 10.26). Congestive heart failure cases with reduced LVEF had an annual mortality of 18.9% versus 4.1% for matched control subjects (adjusted hazards ratio = 4.31, 95% confidence interval 1.98 to 9.36). CONCLUSIONS: Normal LV systolic function is often found in persons with CHF in the community and is more common in women than in men. Although CHF cases with normal LVEF have a lower mortality risk than cases with reduced LVEF, they have a fourfold mortality risk compared with control subjects who are free of CHF.

Adult↗

PubMed1999

Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency.

UNLABELLED: Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. BACKGROUND: Little is known about the prevalence of cardiovascular disease (CVD) and associated risk factors in individuals with mild renal insufficiency (RI). Furthermore, the long-term outcomes associated with mild RI in the community have not been described. METHODS: Serum creatinine (SCr) was measured in 6233 adult participants of the Framingham Heart Study (mean age 54 years, 54% women). Mild RI was defined as SCr 136 to 265 micromol/liter (1.5 to 3.0 mg/dl) in men and 120 to 265 micromol/liter (1.4 to 3.0 mg/dl) in women. The lower limits for mild RI were defined by the sex-specific 95th percentile SCr values in a healthy subgroup of our sample. The upper limit for mild RI was chosen to exclude those subjects with more advanced renal failure. Cox proportional hazards analyses were used to determine the relationship of baseline RI to CVD and all-cause mortality. RESULTS: At baseline, 8.7% of men (N = 246) and 8.0% of women (N = 270) had mild RI. Nineteen percent of the subjects with mild RI had prevalent CVD. During 15 years of follow-up, there were 1000 CVD events and 1406 deaths. In women, mild RI was not associated with increased risk for CVD events [hazards ratio (HR) 1.04, 95% CI, 0.79 to 1.37] or all-cause mortality (HR 1.08, 95% CI, 0.87 to 1.34). In men, mild RI showed no significant associations with CVD events (HR 1.17, 95% CI, 0.88 to 1.57), but it was associated with all-cause mortality in age-adjusted (HR 1.42, 95% CI, 1.12 to 1.79) and multivariable adjusted (HR 1.31, 95% CI, 1.02 to 1.67) analyses. CONCLUSION: Mild RI in the community is common and is associated with a high prevalence of CVD. The association of RI with risk for adverse outcomes is strongly related to coexisting CVD and CVD risk factors.

Aged↗

PubMed1999

Differential impact of systolic and diastolic blood pressure level on JNC-VI staging. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

The sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classifies blood pressure into stages on the basis of both systolic (SBP) and diastolic (DBP) blood pressure levels. When a disparity exists between SBP and DBP stages, patients are classified into the higher stage ("up-staged"). We evaluated the effect of disparate levels of SBP and DBP on blood pressure staging and eligibility for therapy. We examined 4962 Framingham Heart Study subjects between 1990 and 1995 and determined blood pressure stages on the basis of SBP alone, DBP alone, or both. After the exclusion of subjects on antihypertensive therapy (n=1306), 3656 subjects (mean age 58+/-13 years; 55% women) were eligible. In this sample, 64.6% of subjects had congruent stages of SBP and DBP, 31.6% were up-staged on the basis of SBP, and 3.8% on the basis of DBP; thus, SBP alone correctly classified JNC-VI stage in approximately 96% (64.6%+31.6%) of the subjects. Among subjects >60 years of age, SBP alone correctly classified 99% of subjects; in those </=60 years old, SBP alone correctly classified 95%. Of 1488 subjects with high-normal blood pressure or hypertension, who were potentially eligible for drug therapy, 13.0% had congruent elevations of SBP and DBP, 77.7% were up-staged on the basis of SBP, and 9.3% were up-staged on the basis of DBP; SBP alone correctly classified 91%, whereas DBP alone correctly classified only 22%. SBP elevation out of proportion to DBP is common in middle-aged and older persons. SBP appears to play a greater role in the determination of JNC-VI blood pressure stage and eligibility for therapy. Given these results, combined with evidence from hypertension treatment trials, future guidelines might consider a greater role for SBP than for DBP in determining the presence of hypertension, risk of cardiovascular events, eligibility for therapy, and benefits of treatment.

Adult↗

PubMed1999

Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes.

The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic beta cell. A dominant-negative frameshift mutation in the IPF-l gene was identified in a single family and shown to cause pancreatic agenesis when homozygous and maturity-onset diabetes of the young (MODY) when heterozygous. We studied the role of IPF-1 in Caucasian diabetic and nondiabetic subjects from the United Kingdom. Three novel IPF-1 missense mutations (C18R, D76N, and R197H) were identified in patients with type 2 diabetes. Functional analyses of these mutations demonstrated decreased binding activity to the human insulin gene promoter and reduced activation of the insulin gene in response to hyperglycemia in the human beta-cell line Nes2y. These mutations are present in 1% of the population and predisposed the subject to type 2 diabetes with a relative risk of 3.0. They were not highly penetrant MODY mutations, as there were nondiabetic mutation carriers 25-53 years of age. We conclude that mutations in the IPF-1 gene may predispose to type 2 diabetes and are a rare cause of MODY and pancreatic agenesis, with the phenotype depending upon the severity of the mutation.

Adult↗

PubMed1999

Parent-offspring trios: a resource to facilitate the identification of type 2 diabetes genes.

The transmission disequilibrium test with use of trios (an affected proband with both parents) is a robust method for assessing the role of gene variants in disease that avoids the problem of population stratification that may confound conventional case/control studies and allows the detection of parent-of-origin effects. Trios have played a major role in defining genes in a number of polygenic conditions, including type 1 diabetes. We assessed the prevalence, clinical characteristics, and suitability for defining type 2 susceptibility genes of European type 2 diabetes trios. In a Caucasian population in the U.K., only 2.5% of type 2 patients had both parents alive. Using a nationwide strategy, we collected 182 trios defined by strict clinical criteria. Immunological and genetic testing resulted in the exclusion of 25 trios as a result of latent autoimmune diabetes (n = 13), inconsistent family relationships (n = 7), and maternally inherited diabetes and deafness (n = 5). The 157 remaining probands had similar treatment requirements to familial type 2 diabetic subjects but presented at a younger age, were more obese, and more frequently had affected parents. Using this resource, we have not found any evidence for linkage disequilibrium between type 2 diabetes and the glucokinase gene markers GCK1 and GCK2 and the chromosome 20 marker D20S197. We conclude that European type 2 diabetes trios are difficult to collect but provide an important additional approach to dissecting the genetics of type 2 diabetes.

Adult↗

PubMed1998

Calcium antagonists and mortality risk in men and women with hypertension in the Framingham Heart Study.

BACKGROUND: Several recent studies have suggested that calcium antagonist drugs, which are widely used for the treatment of hypertension, are associated with increased risk of cardiovascular disease. These studies have cast doubts on the long-term safety of calcium antagonists. OBJECTIVE: To examine the association of calcium antagonist use with mortality in subjects with hypertension followed up in the Framingham Heart Study. SUBJECTS AND METHODS: We stratified 3539 subjects (mean+/-SD age, 64+/-13 years) from the Framingham Heart Study who had hypertension at routine clinic examinations, according to the use of calcium antagonists and presence of coronary heart disease at the baseline examination. At each follow-up examination (every 2-4 years), subjects were reclassified with regard to the use of calcium antagonists. The end point of the study was all-cause mortality. Hazard ratios and 95% confidence intervals associated with the use of calcium antagonists were obtained using Cox proportional hazards regression models. RESULTS: There were 970 deaths during follow-up. Hazard ratios for mortality associated with the use of calcium antagonists were 0.93 (95% confidence interval, 0.72-1.21; P=.59) for subjects with hypertension without coronary heart disease, and 0.92 (95% confidence interval, 0.69-1.24; P=.58) for those with coronary heart disease at baseline. All models were adjusted for age, sex, current smoking, systolic and diastolic blood pressure, use of beta-blockers, and use of other antihypertensive medications. CONCLUSIONS: In this cohort of 3539 subjects with hypertension there were no differences in mortality among subjects with hypertension using a calcium antagonist compared with those who were not. Results were similar among subjects with hypertension with and without coronary heart disease. The results of ongoing long-term, randomized clinical trials will provide more definitive data on the safety of calcium antagonists.

Adult↗

PubMed1998

Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study.

Heart rate variability (HRV) is a useful noninvasive tool to assess cardiac autonomic function. The purpose of this study was to (1) compare measures of HRV between hypertensive and normotensive subjects and (2) examine the role of HRV as a predictor of new-onset hypertension. The first 2 hours of ambulatory ECG recordings obtained from 931 men and 1111 women attending a routine examination at the Framingham Heart Study were processed for HRV. Three time-domain and 5 frequency-domain variables were studied: standard deviation of normal RR intervals (SDNN), percentage of differences between adjacent normal RR intervals exceeding 50 milliseconds, square root of the mean of squared differences between adjacent normal RR intervals, total power (0.01 to 0.40 Hz), high frequency power (HF, 0.15 to 0.40 Hz), low frequency power (LF, 0.04 to 0.15 Hz), very low frequency power (0.01 to 0.04 Hz), and LF/HF ratio. On cross-sectional analysis, HRV was significantly lower in hypertensive men and women. Among 633 men and 801 women who were normotensive at baseline (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg and not receiving antihypertensive treatment), 119 men and 125 women were newly hypertensive at follow-up 4 years later. After adjustment for factors associated with hypertension, multiple logistic regression analysis revealed that LF was associated with incident hypertension in men (odds ratio per SD decrement [OR], 1.38; 95% confidence interval [CI], 1.04 to 1.83) but not in women (OR, 1.12; 95% CI, 0.86 to 1.46). SDNN, HF, and LF/HF were not associated with hypertension in either sex. HRV is reduced in men and women with systemic hypertension. Among normotensive men, lower HRV was associated with greater risk for developing hypertension. These findings are consistent with the hypothesis that autonomic dysregulation is present in the early stage of hypertension.

Adult↗

PubMed1998

Segregation analysis of pulmonary function among families in the Framingham Study.

Familial aggregation of cross-sectional pulmonary function was examined in 5,003 subjects from 1,408 families participating in the Framingham Study. Subjects, who were members of either the Original Cohort (recruited from 1948 to 1952) or the Offspring Cohort (recruited from 1971 to 1974), underwent spirometry at a mean age of 53 yr. The effects of age, height, weight, and smoking status on FEV1 were evaluated through linear-regression analysis, with separate models for men and women in each cohort. The gender- and cohort-specific standardized residual FEV1 from these models was used as the phenotypic variable in familial correlation and segregation analyses to assess inheritance patterns. In models that assumed no major gene determining FEV1, correlation of pulmonary function was greater for mothers and offspring than for fathers and offspring (p[mo] = 0.190, p[fo] = 0.112; p = 0.06), and sibling correlation exceeded parent-offspring correlation (p[sib] = 0.225; p < 0.01). By comparison with a general model, in which transmission probabilities and residual familial correlations are arbitrary, models that imposed a Mendelian gene were rejected (p < 0.001). A model with no parent-offspring transmission of a major factor, but with residual familial correlation, provided as good a fit as the general model, suggesting that environmental and/or polygenic genetic influences determine FEV1.

Body Height↗

PubMed1997

Distribution and categorization of echocardiographic measurements in relation to reference limits: the Framingham Heart Study: formulation of a height- and sex-specific classification and its prospective validation.

BACKGROUND: Despite widespread categorization of echocardiographic measurements, there are no standardized guidelines for partitioning values exceeding reference limits. METHODS AND RESULTS: We used regression analyses to develop sex- and height-specific reference limits for cardiac M-mode measurements (left ventricular [LV] mass, LV wall thickness, and LV and left atrial dimensions) in a healthy reference sample (n=1099) from the Framingham Heart Study. We then examined the distribution of measurements in a broad sample (n=4957) and classified the measurements according to increasing deviation from the height- and sex-specific reference limits and the 95th, 98th, and 99th percentile values for the broad sample (categories 0 through 4, respectively). To validate the categorization scheme, we used multivariable proportional-hazards regression to assess the relations of LV mass and LV wall thickness categories to risk of cardiovascular events and the relations of left atrial size to risk of atrial fibrillation. During a mean follow-up period of 7.7 years, 587 subjects developed new cardiovascular disease events, and 166 subjects developed new-onset atrial fibrillation. After adjustment for known risk factors, there was a 1.2- and 1.3-fold risk of cardiovascular disease events per category of LV wall thickness and LV mass, respectively, and a 1.6-fold risk of atrial fibrillation per category of left atrial size. CONCLUSIONS: Using a large community-based study sample, we propose a classification scheme that provides a standardized and validated framework for partitioning echocardiographic measurements. If adopted, the categorization scheme should promote uniformity in describing measurements among echocardiographic laboratories and enhance the comprehensibility of measurements to clinicians.

Adolescent↗

PubMed1997

Left ventricular dilatation and the risk of congestive heart failure in people without myocardial infarction.

BACKGROUND: Left ventricular dilatation is a well-recognized precursor of ventricular dysfunction and congestive heart failure after myocardial infarction. The effect of left ventricular dilatation on the risk of heart failure in people initially free of myocardial infarction is not known. METHODS: We examined the relation of the left ventricular end-diastolic and end-systolic internal dimensions, as measured by M-mode echocardiography, to the risk of congestive heart failure in 4744 subjects (2083 men and 2661 women) who had not sustained a myocardial infarction and who were free of congestive heart failure. We used sex-stratified proportional-hazards regression to assess the association between base-line left ventricular internal dimensions and the subsequent risk of congestive heart failure, after adjusting for age, blood pressure, hypertension treatment, body-mass index, diabetes, valve disease, and interim myocardial infarction. RESULTS: Over an 11-year follow-up period, congestive heart failure developed in 74 subjects (38 men and 36 women). The risk-factor-adjusted hazard ratio for congestive heart failure was 1.47 (95 percent confidence interval, 1.25 to 1.73) for an increment of 1 SD in the left ventricular end-diastolic dimension, indexed for height. We obtained similar results using the left ventricular end-systolic dimension (hazard ratio, 1.43; 95 percent confidence interval, 1.24 to 1.65). CONCLUSIONS: An increase in left ventricular internal dimension is a risk factor for congestive heart failure in men and women who have not had a myocardial infarction. Knowledge of the left ventricular dimension improves predictions of the risk of congestive heart failure made on the basis of traditional risk factors, perhaps by aiding in the identification of subjects with subclinical left ventricular dysfunction.

Female↗

PubMed1997

Antecedent hypertension confers increased risk for adverse outcomes after initial myocardial infarction.

Several studies have examined the association of blood pressure (BP) after myocardial infarction (MI) with a risk for adverse outcome; however, few studies have investigated prognosis after MI as a function of BP before MI. Our goal was to examine the relation of antecedent hypertension to risk of adverse outcomes after initial MI. From 1967 to 1990, 404 subjects followed at the Framingham Heart Study developed an initial MI. These subjects were classified on the basis of preinfarction BP into normotensive (BP<140/90 mm Hg and not receiving antihypertensive treatment; n=118), stage I-untreated hypertension (BP 140 to 159/90 to 99 mm Hg; n=89), and stage II to IV or treated hypertension (BP > or =160/100 mm Hg or treated hypertension; n=197). Cox models were used to adjust for age, sex, smoking, glucose intolerance, total cholesterol, and prior cardiovascular disease. Antecedent hypertension was related to risk of adverse outcome after MI. Compared with normotensive individuals, stage II to IV hypertensives were at increased risk for reinfarction (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.20 to 4.04). A similar but nonsignificant association was seen in stage I hypertensives (HR, 1.91; 95% CI, 0.97 to 3.77). Stage II to IV hypertensives were at increased risk for all-cause mortality compared with normotensive persons (HR, 1.45; 95% CI, 1.07 to 1.98). Thus, even after MI, a history of antecedent hypertension remains predictive of adverse outcome. These findings are consistent with beneficial effects of BP control in primary and secondary prevention settings. Effective BP control may both reduce the risk for an initial MI and improve outcome in the event that an MI occurs.

Aged↗

PubMed1997

Pain behaviors in LBW infants accompany some "nonpainful" caregiving procedures.

Painful procedures may lead to both long- and short-term complications in low birth weight (LBW) infants. This study investigated neonatal pain responses (grimace, slight cry expression, increased cry expression, and knee/leg flexion) during six painful and three nonpainful procedures. The 30 LBW infants studied were less than 48 hours of age and less than 34 weeks gestation, with a mean birth weight of 1,320 gm. The design was comparative; data analysis included repeated measures of analysis of variance, independent t-tests, and paired t-tests. The four pain responses were found to be present 75 to 100 percent of the time after painful procedures (suctioning, skin puncture, dressing change or removal, discontinuation of intravenous line, and insertion of a nasogastric tube). They were also found to be present 49 to 69 percent of the time after nonpainful procedures (total position change, addition/withdrawal of fluid from umbilical catheter, and IV administration of medication).

Humans↗

PubMed1996

Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study.

BACKGROUND: Although heart rate variability (HRV) is altered in a variety of pathological conditions, the association of reduced HRV with risk for new cardiac events has not been studied in a large community-based population. METHODS AND RESULTS: The first 2 hours of ambulatory ECG recordings obtained on subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease or congestive heart failure were reprocessed to assess HRV. Five frequency-domain measures and three time-domain measures were obtained. The associations between HRV measures and the incidence of new cardiac events (angina pectroris, myocardial infarction, coronary heart disease death, or congestive heart failure) were assessed with proportional hazards regression analyses. There were 2501 eligible subjects with a mean age of 53 years. During a mean follow-up of 3.5 years, cardiac events occurred in 58 subjects. After adjustment for age, sex, cigarette smoking, diabetes, left ventricular hypertrophy, and other relevant risk factors, all HRV measures except the ratio of low-frequency to high-frequency power were significantly associated with risk for a cardiac event (P = .0016 to .0496). A one-standard deviation decrement in the standard deviation of total normal RR intervals (natural log transformed) was associated with a hazard ratio of 1.47 for new cardiac events (95% confidence interval of 1.16 to 1.86). CONCLUSIONS: The estimation of HRV by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional cardiovascular disease risk factors.

Adult↗

PubMed1996

Determinants of heart rate variability.

OBJECTIVES: This study sought to examine clinical determinants of heart rate variability and to report normative reference values for eight heart rate variability measures. BACKGROUND: Although the clinical implications of heart rate variability have been described, clinical determinants and normative values of heart rate variability measures have not been studied systematically in a large community-based population. METHODS: The first 2 h of ambulatory electrocardiographic recordings obtained in Framingham Heart Study subjects attending a routine examination were reprocessed for heart rate variability. Recordings with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1-h recording time or processed time < 50% of recorded time were excluded; subjects receiving antiarrhythmic medications also were excluded. Among five frequency domain and three time domain measures that were obtained, low frequency power (0.04 to 0.15 Hz), high frequency power (0.15 to 0.40 Hz) and the standard deviation of total normal RR intervals based on 2-h recordings were selected for the principal analyses. Variables with potential physiologic effects or possible technical influences on heart rate variability measures were chosen for multiple linear regression analysis. Normative values, derived from a subset of healthy subjects, were adjusted for age and heart rate. RESULTS: There were 2,722 eligible subjects with a mean age (+/-SD) of 55 +/- 14 years. Three separate multiple linear regression analyses revealed that higher heart rate, older age, beta-adrenergic blocking agent use, history of myocardial infarction or congestive heart failure, diuretic use, diastolic blood pressure > or = 90 mm Hg, diabetes mellitus, consumption of three or more cups of coffee per day and smoking were associated with lower values of one or more heart rate variability measures, whereas longer processed time, start time in the morning, frequent supraventricular and ventricular premature beats, female gender and systolic blood pressure > or = 160 mm Hg were associated with higher values. Age and heart rate were the major determinants of all three selected heart rate variability measures (partial R2 values 0.125 to 0.389). Normative reference values for all eight heart rate variability measures are presented. CONCLUSIONS: Age and heart rate must be taken into account when assessing heart rate variability.

Adult↗

PubMed1996

Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study.

BACKGROUND: Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality. These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome. This investigation was designed to look at the prognostic implications of exercise heart rate response in a population-based sample. METHODS AND RESULTS: In this prospective cohort investigation, 1575 male participants (mean age, 43 years) in the Framingham Offspring Study who were free of coronary heart disease, who were not taking beta-blockers, and who underwent submaximal treadmill exercise testing (Bruce protocol) were studied. Heart rate response was assessed in three ways: (1) failure to achieve 85% of the age-predicted maximum heart rate, which has been the traditional definition of chronotropic incompetence; (2) the actual increase in heart rate from rest to peak exercise; and (3) the ratio of heart rate to metabolic reserve used by stage 2 of exercise ("chronotropic response index"). Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up. Failure to achieve target heart rate occurred in 327 (21%) subjects. During follow-up there were 55 deaths (14 caused by coronary heart disease) and 95 cases of incident coronary heart disease. Failure to achieve target heart rate, a smaller increase in heart rate with exercise, and the chronotropic response index were predictive of total mortality and incident coronary heart disease (P <.01). Failure to achieve target heart rate remained predictive of incident coronary heart disease even after adjusting for age, ST-segment response, physical activity, and traditional coronary disease risk factors (adjusted hazard ratio, 1.75; 95% confidence interval, 1.11 to 2.74; P=.02). After adjusting for the same factors, the increase in exercise heart rate remained inversely predictive of total mortality (P=.04) and coronary heart disease incidence (P=.0003). The chronotropic response index also was predictive of total mortality (P=.05) and incident coronary heart disease (P=.001) after adjusting for age and other risk factors. CONCLUSIONS: An attenuated heart rate response to exercise, a manifestation of chronotropic incompetence, is predictive of increased mortality and coronary heart disease incidence.

Adult↗

PubMed1996

Doppler diastolic filling indexes in relation to disease states.

This study compares mean Doppler-derived diastolic filling indexes in a variety of disease states in a large, population-based sample. Pulse-wave Doppler was used to examine 880 eligible participants of the Framingham Heart Study. Peak velocity of early flow and late flow, ratio of early to late peak velocities, atrial filling fraction, and early filling wave acceleration and deceleration times were obtained. Multiple linear regression analyses were performed comparing mean values for individuals with hypertension, diabetes, coronary disease, cardiovascular disease, and pulmonary disease. Hypertension was associated with a greater peak velocity late flow (0.027 m/sec; 95% confidence interval, 0.006, 0.047; p = 0.011), and diabetes was associated with a larger mean deceleration time (0.12 sec, confidence interval, 0.002, 0.021; p = 0.016). In multivariate analyses, hypertension continued to show a strong association with altered Doppler diastolic filling patterns, p value 0.009, whereas in diabetes, the multivariate p value was 0.28.

Adult↗

PubMed1995

Unexplained gradual-onset Q wave patterns. A case series from the Framingham Study.

Original cohort members of the Framingham Study were studied to determine prognosis associated with unexplained (gradual-onset) Q wave patterns detected on routine electrocardiograms (ECGs). Biennial ECGs were obtained on subjects beginning in 1948. The index ECG was read independently and then serially in relation to all previous tracings for evidence of myocardial infarction. Proportional hazards modeling was used to assess the risk for outcomes in those with unexplained (gradual-onset) Q wave patterns compared with subjects with unrecognized myocardial infarcts (abrupt-onset Q waves) and compared with referent subjects. Unexplained Q wave patterns developed in 53 men and 39 women. Subjects with unexplained Q wave patterns had less than 40% of the risk for myocardial infarction or coronary death as compared with those with unrecognized myocardial infarction after adjusting for risk factors (hazard ratio, 0.38; 95% confidence interval, 0.19, 0.78; P = .008) and a trend toward a lower risk for overall mortality (adjusted hazard ratio, 0.73; 95% confidence interval, 0.46, 1.16; P = .18). Risks for myocardial infarction or coronary death and overall mortality were similar in subjects with unexplained Q wave patterns and referent subjects in the fully adjusted models. Detection of prominent Q waves on an ECG requires comparison with prior tracings to differentiate the unexplained Q wave pattern from the unrecognized infarct, conditions that have significantly different prognostic implications.

Aged↗