Glyburide increases risk in patients with diabetes mellitus after emergent percutaneous intervention for myocardial infarction — A nationwide study

Background

Sulfonylureas have been linked to an increased cardiovascular risk by inhibition of myocardial preconditioning. Whether individual sulfonylureas affect outcomes in diabetic patients after emergent percutaneous coronary intervention for myocardial infarction is unknown.

Methods

All Danish patients receiving glucose-lowering drugs admitted with myocardial infarction between 1997 and 2006 who underwent emergent percutaneous coronary intervention were identified from national registers. Multivariable Cox proportional hazards models were used to analyze the risk of cardiovascular mortality and morbidity associated with sulfonylureas.

Results

A total of 926 patients were included and 163 (17.6%) patients died during the first year of which 155 (16.7%) were cardiovascular deaths. The most common treatment was sulfonylureas which were received by 271 (29.3%) patients, and 129 (13.9%) received metformin. Cox proportional hazard regression analyses adjusted for age, sex, calendar year, comorbidity and concomitant pharmacotherapy showed an increased risk of cardiovascular mortality (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.26-6.72 ; p = 0.012), cardiovascular mortality and nonfatal myocardial infarction (HR 2.69 , 95% CI 1.21-6.00; p = 0.016), and all-cause mortality (HR 2.46, 95% CI 1.11-5.47; p = 0.027), respectively, with glyburide compared to metformin.

Conclusions

Glyburide is associated with increased cardiovascular mortality and morbidity in patients with diabetes mellitus undergoing emergent percutaneous coronary intervention after myocardial infarction. Early reperfusion therapy is the mainstay in modern treatment of myocardial infarction and the time may have come to discard glyburide in favour of sulfonylureas that do not appear to confer increased cardiovascular risk.     

Left ventricular hypertrophy and cardiovascular mortality by race and ethnicity

Background

Left ventricular hypertrophy is a major independent risk factor for cardiovascular mortality. The contribution of left ventricular hypertrophy to racial and ethnic differences in cardiovascular mortality is poorly understood.

Methods

We used data from the Third National Health and Nutrition Examination Survey and from the National Death Index to compare mortality for those with an electrocardiographic (ECG) diagnosis of left ventricular hypertrophy to those without left ventricular hypertrophy separately for whites, African Americans, and Latinos. We used Cox proportional hazards regression to control for other known prognostic factors.

Results

ECG left ventricular hypertrophy was significantly associated with 10-year cardiovascular mortality in all 3 racial/ethnic groups, both unadjusted and adjusted for other known prognostic factors. The hazard ratio for this association was significantly greater for African Americans (2.31; 95% confidence interval [CI], 1.55-3.42) than for whites and Latinos (1.32; 95% CI, 1.14-1.76 and 2.11; 95% CI, 1.35-3.30, respectively), independent of systolic blood pressure.

Conclusions

ECG left ventricular hypertrophy contributes more to the risk of cardiovascular mortality in African Americans than it does in whites. Using regression of ECG left ventricular hypertrophy as a goal of therapy might be a means to reduce racial differences in cardiovascular mortality; prospective validation is required.     

Migraines, angiographic coronary artery disease and cardiovascular outcomes in women

Purpose

There are conflicting data regarding the association between migraines and cardiovascular events. We evaluated the relationship between migraine headaches, angiographic coronary artery disease, and cardiovascular events in women.

Subjects and Methods

The Women’s Ischemia Syndrome Evaluation (WISE) study is a National Heart, Lung and Blood Institute (NHLBI)-sponsored prospective, multicenter study aiming to improve ischemia evaluation in women. A total of 944 women presenting with chest pain or symptoms suggestive of myocardial ischemia were enrolled and underwent complete demographic, medical, and psychosocial history, physical examination, and coronary angiography testing. A smaller subset of 905 women, representing a mean age of 58 years, answered questions regarding a history of migraines. We prospectively followed 873 women for 4.4 years for cardiovascular events and all-cause mortality.

Results

Women reporting a history of migraines (n = 220) had lower angiographic coronary severity scores, and less severe (≥ 70% luminal stenosis) angiographic coronary artery disease compared to women without a history of migraines (n = 685). These differences remained statistically significant after adjustment for age and other important cardiac risk factors. On prospective follow-up of a median of 4.4 years, women with a history of migraines were not more likely to have a cardiovascular event (hazard ratio [HR] 1.2; 95% confidence interal [CI], 0.93-1.58) and migraines did not predict all-cause mortality (HR 0.96; 95% CI, 0.49-1.99).

Conclusion

Among women undergoing coronary angiography for suspected ischemia, those reporting migraines had less severe angiographic coronary artery disease. We could not support an association between migraines and cardiovascular events or death. Further research studying the common pathophysiology underlying migraines and cardiovascular disease is warranted.     

Turning back the clock: adopting a healthy lifestyle in middle age

Purpose

To determine the frequency of adopting a healthy lifestyle (5 or more fruits and vegetables daily, regular exercise, BMI 18.5-29.9 kg/m², no current smoking) in a middle-aged cohort, and determine the subsequent rates of cardiovascular disease (CVD) and mortality among those who adopt a healthy lifestyle.

Methods

We conducted a cohort study in a diverse sample of adults age 45-64 in the Atherosclerosis Risk in Communities survey. Outcomes are all-cause mortality and fatal or non-fatal cardiovascular disease.

Results

Of 15,708 participants, 1344 (8.5%) had 4 healthy lifestyle habits at the first visit, and 970 (8.4%) of the remainder had newly adopted a healthy lifestyle 6 years later. Men, African Americans, individuals with lower socioeconomic status, or a history of hypertension or diabetes were less likely to newly adopt a healthy lifestyle (all P <.05). During the following 4 years, total mortality and cardiovascular disease events were lower for new adopters (2.5% vs 4.2%, χ²P <.01, and 11.7% vs 16.5%, χ²P <.01 respectively) compared to individuals who did not adopt a healthy lifestyle. After adjustment, new adopters had lower all-cause mortality (OR 0.60, 95% Confidence Interval [CI], 0.39-0.92) and fewer cardiovascular disease events (OR 0.65, 95% CI, 0.39-0.92) in the next 4 years.

Conclusions

People who newly adopt a healthy lifestyle in middle-age experience a prompt benefit of lower rates of cardiovascular disease and mortality. Strategies to encourage adopting healthy lifestyles should be implemented, especially among people with hypertension, diabetes, or low socioeconomic status.     

Sodium intake and mortality in the NHANES II follow-up study

Purpose

US Dietary Guidelines recommend a daily sodium intake <2300 mg, but evidence linking sodium intake to mortality outcomes is scant and inconsistent. To assess the association of sodium intake with cardiovascular disease (CVD) and all-cause mortality and the potential impact of dietary sodium intake <2300 mg, we examined data from the Second National Health and Nutrition Examination Survey (NHANES II).

Methods

Observational cohort study linking sodium, estimated by single 24-hour dietary recall and adjusted for calorie intake, in a community sample (n = 7154) representing 78.9 million non-institutionalized US adults (ages 30-74). Hazard ratios (HR) for CVD and all-cause mortality were calculated from multivariable adjusted Cox models accounting for the sampling design.

Results

Over mean 13.7 (range: 0.5-16.8) years follow-up, there were 1343 deaths (541 CVD). Sodium (adjusted for calories) and sodium/calorie ratio as continuous variables had independent inverse associations with CVD mortality (P = .03 and P = .008, respectively). Adjusted HR of CVD mortality for sodium <2300 mg was 1.37 (95% confidence interval [CI]: 1.03-1.81, P = .033), and 1.28 (95% CI: 1.10-1.50, P = .003) for all-cause mortality. Alternate sodium thresholds from 1900-2700 mg gave similar results. Results were consistent in the majority of subgroups examined, but no such associations were observed for those <55 years old, non-whites, or the obese.

Conclusion

The inverse association of sodium to CVD mortality seen here raises questions regarding the likelihood of a survival advantage accompanying a lower sodium diet. These findings highlight the need for further study of the relation of dietary sodium to mortality outcomes.     

Risk of mortality with vitamin E supplements: the Cache County study

Purpose

A recent meta-analysis reported increased mortality in clinical trial participants randomized to high-dose vitamin E. We sought to determine whether these mortality risks with vitamin E reflect adverse consequences of its use in the presence of cardiovascular disease.

Methods

In a defined population aged 65 years or older, baseline interviews captured self- or proxy-reported history of cardiovascular illness. A medicine cabinet inventory verified nutritional supplement and medication use. Three sources identified subsequent deaths. Cox proportional hazards methods examined the association between vitamin E use and mortality.

Results

After adjustment for age and sex, there was no association in this population between vitamin E use and mortality (adjusted hazard ratio [aHR] 0.93; 95% confidence interval [CI], 0.74-1.15). Predictably, deaths were more frequent with a history of diabetes, stroke, coronary artery bypass graft surgery, or myocardial infarction, and with the use of warfarin, nitrates, or diuretics. None of these conditions or treatments altered the null main effect with vitamin E, but mortality was increased in vitamin E users who had a history of stroke (aHR 3.64; CI, 1.73-7.68), coronary bypass graft surgery (aHR 4.40; CI, 2.83-6.83), or myocardial infarction (aHR 1.95; CI, 1.29-2.95) and, independently, in those taking nitrates (aHR 3.95; CI, 2.04-7.65), warfarin (aHR 3.71; CI, 2.22-6.21), or diuretics (aHR 1.83; CI, 1.35-2.49). Although not definitive, a consistent trend toward reduced mortality was seen in vitamin E users without these conditions or treatments.

Conclusions

In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without.     

Prognostic Significance of Quantitative QRS Duration

Background

Although QRS duration is known to be a predictor of mortality in patients with left ventricular dysfunction, our purpose was to evaluate the prognostic power of computer-measured QRS duration in a general medical population.

Methods

Analyses were performed on the first electrocardiogram digitally recorded on 46,933 consecutive patients at the Palo Alto Veterans Affairs Medical Center between 1987 and 2000. Patients with electrocardiograms exhibiting Wolff-Parkinson-White were excluded (n = 44), and those with bundle branch block or electronic pacing were considered separately, leaving 44,280 patients for analysis (mean age 56 ± 15 years; 90% were males). There were 3659 (8.3%) cardiovascular deaths (mean follow-up of 6.0 ± 3.8 years).

Results

A survival plot showed significant separation according to a QRS duration score. After adjustment in the Cox model for age, gender, and heart rate, the QRS duration score was a strong independent predictor of cardiovascular mortality. For every 10-ms increase in QRS duration, there was an 18% increase in cardiovascular risk. The results were similar in patients with an abnormal electrocardiogram, a bundle branch block, and a paced rhythm.

Conclusion

Quantitative QRS duration was a significant and independent predictor of cardiovascular mortality in a general medical population.     

Time-dependent impact of diabetes on the mortality of patients on renal replacement therapy: a population-based study in Germany (2002-2009)

Aims

To estimate the impact of diabetes on the mortality of patients with incident renal replacement therapy (RRT).

Methods

We assessed the mortality of 544 incident RRT patients aged ≥30 years between 2002 and 2009 (57.9% men, mean age 70.3 years, 49.6% patients with diabetes) by analyzing the data of all dialysis centers covering a German region. We compared the estimated time-dependent hazard ratios of patients with and without diabetes by using the Cox proportional-hazards regression model.

Results

Overall, 319 patients had died (158 diabetic), approximately 50% after 3 years. Up to about 3 years, the mortality rate was lower in diabetic than in nondiabetic patients. Thereafter, the survival curves crossed (interaction diabetes × time, p = 0.002; adjusted hazard ratios for diabetes: baseline, 0.66; year 1, 0.84; year 2, 1.05; year 3, 1.33; year 4, 1.68). The results were similar in men and women; however, the interaction of diabetes and time was significant only in men (p = 0.004). Further significant risk factors of mortality were age, sex, initial central venous catheter, cardiovascular disease, and malignancy.

Conclusions

In this population-based study, the influence of diabetes was time-dependent, with a lower mortality in diabetic versus non-diabetic patients in the first three years but a higher mortality in these patients after 3 years. Results were similar in men and women.     

Higher Cardiovascular Disease Prevalence and Mortality among Younger Blacks Compared to Whites

Background

Blacks have higher rates of cardiovascular disease than whites. The age at which these differential rates emerge has not been fully examined.

Objective

We examined cardiovascular disease prevalence and mortality among black and white adults across the adult age spectrum and explored potential mediators of these differential disease prevalence rates.

Methods

We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey data from 1999-2006. We estimated age-adjusted and age-specific prevalence ratios (PR) for cardiovascular disease (heart failure, stroke, or myocardial infarction) for blacks versus whites in adults aged 35 years and older and examined potential explanatory factors. From the National Compressed Mortality File 5-year aggregate file of 1999-2003, we determined age-specific cardiovascular disease mortality rates.

Results

In young adulthood, cardiovascular disease prevalence was higher in blacks than whites (35-44 years PR 1.9; 95% confidence interval [CI], 1.1-3.4). The black-white PR decreased with each decade of advancing age (P for trend = .04), leading to a narrowing of the racial gap at older ages (65-74 years PR 1.2; 95% CI, 0.8-1.6; ≥75 years PR 1.0; 95% CI, 0.7-1.4). Clinical and socioeconomic factors mediated some, but not all, of the excess cardiovascular disease prevalence among young to middle-aged blacks. Over a quarter (28%) of all cardiovascular disease deaths among blacks occurred in those aged <65 years, compared with 13% among whites.

Conclusions

Reducing black/white disparities in cardiovascular disease will require a focus on young and middle-aged blacks.     

Mortality, incidence of cardiovascular diseases, and educational level among the diabetic and non-diabetic populations in two large Italian cities

Aims

We investigated if diabetes modifies the effect of the association of education with mortality and incidence of cardiovascular diseases.

Methods

We identified 44,889 diabetics using multiple data sources. They were followed up from January 2002 up to December 2005, and their mortality, incidence of myocardial infarction and stroke, by educational level were analysed, and compared with those of the local non-diabetic population.

Results

The all-cause Standardized Mortality Ratios among diabetics, compared with non-diabetics, were 170 for men and 175 for women. Standardized Incidence Ratios were 199 for myocardial infarction, and 183 for stroke in men and, respectively, 281, and 179 in women. Among non-diabetics there was a clear inverse relation with educational level for all outcomes, whereas among diabetics no significant social difference in incidence was found; slight social differences in mortality were present among men, but not among women. The effect of diabetes on social differences was enhanced in the youngest population.

Conclusions

Diabetes increases the risk of death and the incidence of vascular diseases, but reduces their inverse association with education. This is likely related to the high accessibility and good quality of health care provided by the local networks of diabetic centres and primary care.     

Diabetes and Coronary Heart Disease as Risk Factors for Mortality in Older Adults

Background

Type 2 diabetes has been described as a coronary heart disease (CHD) “risk equivalent.” We tested whether cardiovascular and all-cause mortality rates were similar between participants with prevalent CHD vs diabetes in an older adult population in whom both glucose disorders and preexisting atherosclerosis are common.

Methods

The Cardiovascular Health Study is a longitudinal study of men and women (n = 5784) aged ≥65 years at baseline who were followed from baseline (1989/1992-1993) through 2005 for mortality. Diabetes was defined by fasting plasma glucose ≥7.0 mmol/L or use of diabetes control medications. Prevalent CHD was determined by confirmed history of myocardial infarction, angina, or coronary revascularization.

Results

Following multivariable adjustment for other cardiovascular disease risk factors and subclinical atherosclerosis, CHD mortality risk was similar between participants with CHD alone vs diabetes alone (hazard ratio [HR] 1.04, 95% confidence interval [CI], 0.83-1.30). The proportion of mortality attributable to prevalent diabetes (population-attributable risk percent = 8.4%) and prevalent CHD (6.7%) was similar in women, but the proportion of mortality attributable to CHD (16.5%) as compared with diabetes (6.4%) was markedly higher in men. Patterns were similar for cardiovascular disease mortality. By contrast, the adjusted relative hazard of total mortality was lower among participants with CHD alone (HR 0.85, 95% CI, 0.75-0.96) as compared with those who had diabetes alone.

Conclusions

Among older adults, diabetes alone confers a risk for cardiovascular mortality similar to that from established clinical CHD. The public health burden of both diabetes and CHD is substantial, particularly among women.     

Adopting moderate alcohol consumption in middle age: subsequent cardiovascular events

Purpose

Moderate alcohol use is part of a healthy lifestyle, yet current guidelines caution nondrinkers against starting to drink alcohol in middle age. The purpose of this study was to evaluate whether adopting moderate alcohol consumption in middle age would result in subsequent lower cardiovascular risk.

Methods

This study examined a cohort of adults aged 45-64 years participating in the Atherosclerosis Risk in Communities study over a 10-year period. The primary outcome was fatal or nonfatal cardiovascular events.

Results

Of 7697 participants who had no history of cardiovascular disease and were nondrinkers at baseline, within a 6-year follow-up period, 6.0% began moderate alcohol consumption (2 drinks per day or fewer for men, 1 drink per day or fewer for women) and 0.4% began heavier drinking. After 4 years of follow-up, new moderate drinkers had a 38% lower chance of developing cardiovascular disease than did their persistently nondrinking counterparts. This difference persisted after adjustment for demographic and cardiovascular risk factors (odds ratio 0.62, 95% confidence interval, 0.40-0.95). There was no difference in all-cause mortality between the new drinkers and persistent nondrinkers (odds ratio 0.71, 95% confidence interval, 0.31-1.64).

Conclusion

People who newly begin consuming alcohol in middle age rarely do so beyond recommended amounts. Those who begin drinking moderately experience a relatively prompt benefit of lower rates of cardiovascular disease morbidity with no change in mortality rates after 4 years.     

Bupropion for smokers hospitalized with acute cardiovascular disease

Purpose

Smoking cessation after myocardial infarction reduces cardiovascular mortality, but many smokers cannot quit despite state-of-the-art counseling intervention. Bupropion is effective for smoking cessation, but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown.

Methods

A five-hospital randomized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion (300 mg) or placebo in 248 smokers admitted for acute cardiovascular disease, primarily myocardial infarction and unstable angina. All subjects had smoking counseling in the hospital and for 12 weeks after discharge. Cotinine-validated 7-day tobacco abstinence, cardiovascular mortality, and new cardiovascular events were assessed at 3 months (end-of-treatment) and 1 year.

Results

Validated tobacco abstinence rates in bupropion and placebo groups were 37.1% vs 26.8% (OR 1.61, 95% CI, 0.94-2.76; P=.08) at 3 months and 25.0% vs 21.3% (OR, 1.23, 95% CI, 0.68-2.23, P=.49) at 1 year. The adjusted odds ratio, after controlling for cigarettes per day, depression symptoms, prior bupropion use, hypertension, and length of stay, was 1.91 (95% CI, 1.06-3.40, P=.03) at 3 months and 1.51 (95% CI, 0.81-2.83) at 1 year. Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year (0% vs 2%), in blood pressure at follow-up, or in cardiovascular events at end-of-treatment (16% vs 14%, incidence rate ratio [IRR]1.22 (95% CI: 0.64-2.33) or 1 year (26% vs 18%, IRR 1.56, 95% CI 0.91-2.69).

Conclusions

Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease.     

Influence of Obesity on Outcomes in Atrial Fibrillation: Yet Another Obesity Paradox

Background

Obese patients have favorable outcomes in congestive heart failure, hypertension, peripheral vascular disease, and coronary artery disease. Obesity also has been linked with increased incidence of atrial fibrillation, but its influence on outcomes in atrial fibrillation patients has not been investigated. The objective of this research is to investigate the effect of obesity on outcomes in atrial fibrillation.

Methods

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study was one of the largest multicenter trials of atrial fibrillation, with 4060 patients. Subjects were randomized to rate versus rhythm-control strategy. We performed a post hoc analysis of the National Heart, Lung and Blood Institute limited access dataset of atrial fibrillation patients who had body mass index (BMI) data available in the AFFIRM study. BMI data were not available on 1542 patients. Patients with BMI ≥18.5 were split into normal (18.5-25), overweight (25-30), and obese (>30) categories as per BMI (kg/m²). Multivariate Cox proportional hazards regression was used on the eligible 2492 patients. End points were all-cause mortality and cardiovascular mortality.

Results

Over three fourths of all patients in our cohort were overweight or obese. There were 304 deaths (103 among normal weight, 108 among overweight, and 93 among obese) and 148 cardiovascular deaths (54 among normal weight, 41 among overweight, and 53 among obese) over a mean period of 3 years of patient follow-up. On multivariate analysis, overweight (hazard ratio [HR] 0.64; 95% confidence interval [CI], 0.48-0.84; P = .001) and obese (HR 0.80; 95% CI, 0.68-0.93; P = .005) categories were associated with lower all-cause mortality as compared with normal weight. Overweight (HR 0.40; 95% CI, 0.26-0.60; P <.001) and obese patients (HR 0.77; 95% CI, 0.62-0.95; P = .01) also had lower cardiovascular mortality as compared with the normal weight patients.

Conclusions

Although in prior studies, obesity has been associated with increased risk of atrial fibrillation, an obesity paradox exists for outcomes in atrial fibrillation. Obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients.     

Mortality after Hospitalization with Mild, Moderate, and Severe Hyponatremia

Background

Hyponatremia is the most common electrolyte abnormality in hospitalized individuals.

Methods

To investigate the association between serum sodium concentration and mortality, we conducted a prospective cohort study of 98,411 adults hospitalized between 2000 and 2003 at 2 teaching hospitals in Boston, Massachusetts. The main outcome measures were in-hospital, 1-year, and 5-year mortality. Multivariable logistic regression and Cox proportional hazards models were used to compare outcomes in patients with varying degrees of hyponatremia against those with normal serum sodium concentration.

Results

Hyponatremia (serum sodium concentration <135 mEq/L) was observed in 14.5% of patients on initial measurement. Compared with patients with normonatremia (135-144 mEq/L), those with hyponatremia were older (67.0 vs 63.1 years, P <.001) and had more comorbid conditions (mean Deyo-Charlson Index 1.9 vs 1.4, P <.001). In multivariable-adjusted models, patients with hyponatremia had an increased risk of death in hospital (odds ratio 1.47, 95% confidence interval [CI], 1.33-1.62), at 1 year (hazard ratio 1.38, 95% CI, 1.32-1.46), and at 5 years (hazard ratio 1.25, 95% CI, 1.21-1.30). The increased risk of death was evident even in those with mild hyponatremia (130-134 mEq/L; odds ratio 1.37, 95% CI, 1.23-1.52). The relationship between hyponatremia and mortality was pronounced in patients admitted with cardiovascular disease, metastatic cancer, and those admitted for procedures related to the musculoskeletal system. Resolution of hyponatremia during hospitalization attenuated the increased mortality risk conferred by hyponatremia.

Conclusion

Hyponatremia, even when mild, is associated with increased mortality.     

Serial evaluation of electrocardiographic left ventricular hypertrophy for prediction of risk in hypertensive patients

Background

Although the presence and severity of electrocardiographic (ECG) left ventricular hypertrophy (LVH) have been associated with an increased risk of cardiovascular (CV) morbidity and mortality, the relationship of regression of ECG LVH during antihypertensive therapy to CV risk has only recently been examined.

Methods

Electrocardiographic LVH was evaluated over time in 9193 hypertensive patients enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension study. Patients were treated with losartan- or atenolol-based regimens and followed with serial ECGs at 6 months and then yearly until death or study end. Electrocardiographic LVH was measured using gender-adjusted Cornell product (RaVL + SV3 [+6 mm in women]) ? QRS duration) and Sokolow-Lyon voltage (SV1 + RV5/6).

Results

After mean (SD) follow-up of 4.8 (0.9) years, the Losartan Intervention for Endpoint Reduction in Hypertension study composite end point of CV death, nonfatal myocardial infarction, or stroke occurred in 1096 patients. In Cox regression models controlling for treatment type, baseline Framingham risk score, baseline, and in-treatment blood pressure and for severity of baseline ECG LVH by Cornell product and Sokolow-Lyon voltage, lower in-treatment ECG LVH by Cornell product and Sokolow-Lyon voltage were associated with 14% and 17% lower rates, respectively, of the composite CV end point: adjusted hazard ratios (HRs) of 0.86 (95% confidence interval [CI], 0.82-0.90; P < .001) for every 1050 mm · ms (1 SD) decrease in Cornell product and 0.83 (95% CI, 0.78-0.88; P < .001) for every 10.5 mm (1 SD) decrease in Sokolow-Lyon voltage. In parallel analyses, lower Cornell product and Sokolow- Lyon voltage were each independently associated with lower risks of CV mortality (HR, 0.78; 95% CI, 0.73-0.83; P < .001; HR, 0.80; 95% CI, 0.73-0.87; P < .001), of myocardial infarction (HR, 0.90; 95% CI, 0.82-0.98; P = .011; HR, 0.90; 95% CI, 0.81-1.00; P = .043), and of stroke (HR, 0.90; 95% CI, 0.84-0.96; P = .002; HR, 0.81; 95% CI, 0.75-0.89; P < .001). Regression of ECG LVH was also associated with significantly reduced risks of sudden cardiac death, new-onset atrial fibrillation, hospitalization for heart failure, and new-onset diabetes mellitus.

Conclusions

Regression of ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria during antihypertensive therapy is associated with lower likelihoods of CV morbidity and mortality, all-cause mortality, and new-onset diabetes, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of ECG LVH may improve prognosis.     

Does a Mediterranean diet reduce the mortality risk associated with diabetes: evidence from the Melbourne Collaborative Cohort Study

Background and aims

Diabetes is a risk factor for cardiovascular disease (CVD), yet southern European migrants to Australia with high rates of type 2 diabetes have relatively low CVD mortality. Our aim was to determine whether a Mediterranean style diet could reduce mortality in people with diabetes.

Methods and results

Participants included 16,610 males and 23,860 females from the Melbourne Collaborative Cohort Study; 25% were born in Greece or Italy, and 2150 had previously been diagnosed with diabetes or had elevated blood glucose at baseline (1990-94). Data on demographic, behavioral and physical risk factors were also collected. A personal Mediterranean Diet Score (MDS) was calculated using data from a validated 121-item food frequency questionnaire. Total and CVD mortality data were available up to 2003.Diabetes (new and known) at baseline, was associated with total mortality (men HR 1.43, 95%CI 1.26-1.62; women HR 1.86 95%CI 1.58-2.18), and CVD mortality (men HR 1.53, 95%CI 1.21-1.94; women HR 2.10 95%CI 1.48-2.97) in multivariate models. There was no evidence that glucose tolerance modified the associations between MDS and total or CVD mortality (p interaction all > 0.16). The HRs for total mortality per unit of MDS were 0.96 (95% CI 0.93-0.99) in men and 0.94 (95% CI 0.92-0.97) in women. The HRs for CVD mortality per unit of MDS were 0.94 (95% CI 0.89-0.99) in men and 0.94 (95% CI 0.87-1.01) in women.

Conclusion

Our results add to the evidence supporting the benefit of a Mediterranean style diet for people with type 2 diabetes.     

Metabolic syndrome and risk of cardiovascular disease: a meta-analysis

Purpose

The use of different definitions of the metabolic syndrome has led to inconsistent results on the association between the metabolic syndrome and risk of cardiovascular disease. We examined the association between the metabolic syndrome and risk of cardiovascular disease.

Methods

A MEDLINE search (1966-April 2005) was conducted to identify prospective studies that examined the association between the metabolic syndrome and risk of cardiovascular disease. Information on sample size, participant characteristics, metabolic syndrome definition, follow-up duration, and endpoint assessment was abstracted.

Results

Data from 21 studies met the inclusion criteria and were included. Individuals with the metabolic syndrome, compared to those without, had an increased mortality from all causes (relative risk [RR] 1.35; 95% confidence interval [CI], 1.17-1.56) and cardiovascular disease (RR 1.74; 95% CI, 1.29-2.35); as well as an increased incidence of cardiovascular disease (RR 1.53; 95% CI, 1.26-1.87), coronary heart disease (RR 1.52; 95% CI, 1.37-1.69) and stroke (RR 1.76; 95% CI, 1.37-2.25). The relative risk of cardiovascular disease associated with the metabolic syndrome was higher in women compared with men and higher in studies that used the World Health Organization definition compared with studies that used the Adult Treatment Panel III definition.

Conclusion

This analysis strongly suggests that the metabolic syndrome is an important risk factor for cardiovascular disease incidence and mortality, as well as all-cause mortality. The detection, prevention, and treatment of the underlying risk factors of the metabolic syndrome should become an important approach for the reduction of the cardiovascular disease burden in the general population.     

Elevated resting heart rate is associated with greater risk of cardiovascular and all-cause mortality in current and former smokers

Background

Elevated resting heart rate is associated with mortality in general populations. Smokers may be at particular risk. The association between resting heart rate (RHR), smoking status and cardiovascular and total mortality was investigated in a general population.

Methods

Prospective study of 16,516 healthy subjects from the Copenhagen City Heart Study. 8709 deaths, hereof 3821 cardiovascular deaths, occurred during 33 years of follow-up.

Results

In multivariate Cox models with time-dependent covariates RHR was significantly associated with both cardiovascular and total mortality. Current and former smokers had, irrespective of tobacco consumption, greater relative risk of elevated RHR compared to never smokers. The relative risk of all-cause mortality per 10 bpm increase in RHR was (95% CI): 1.06 (1.01-1.10) in never smokers, 1.11 (1.07-1.15) in former smokers, 1.13 (1.09-1.16) in moderate smokers, and 1.13 (1.10-1.16) in heavy smokers. There was no gender difference. The risk estimates for cardiovascular and all-cause mortality were essentially similar.In univariate analyses, the difference in survival between a RHR in the highest (> 80 bpm) vs lowest quartile (< 65 bpm) was 4.7 years in men and 3.6 years in women. In multivariate analyses, the difference was about one year in never smokers and about two years in current and former smokers.

Conclusions

In a healthy population resting heart rate is associated with total and cardiovascular mortality. Elevated resting heart rate is associated with greater risk in subjects with a history of smoking than in never smokers.     

C-reactive protein, inflammatory conditions, and cardiovascular disease risk

Background

It is uncertain to what extent high C-reactive protein (CRP) concentrations reflect the presence of inflammatory conditions in the community.

Methods

We evaluated 3782 Framingham Offspring Study participants (mean age 55 years; 52% women) free of baseline cardiovascular disease. Logistic regression models examined the prevalence of common inflammatory conditions by CRP categories, while a separate matched case-referent analysis evaluated the prevalence of uncommon inflammatory conditions. Cox models were used to assess the influence of common inflammatory conditions on relations between CRP and incident cardiovascular disease.

Results

Common inflammatory conditions were reported by nearly half of the participants; these individuals were more likely to have markedly high CRP concentrations (>10 mg/L, P for trend = .001). In multivariable models, there were increased odds of having at least one common inflammatory condition with CRP concentrations of 1-3.0, 3.01-10, and >10 mg/L, compared with the referent category (<1 mg/L); the respective odds ratios with 95% confidence intervals were 1.41 (1.07-1.86), 1.45 (1.07-1.98), and 1.64 (1.09-2.47) in men, and 1.08 (0.82-1.43), 1.07 (0.80-1.44), and 1.38 (0.97-1.96) in women. In case-referent analyses, uncommon inflammatory conditions were more common in individuals with CRP >10 mg/L compared with those with CRP <1 mg/L (12.1% vs 6.6%; P = .0001). In multivariable models, higher CRP categories were not associated with incident cardiovascular disease, and with additional adjustment for inflammatory conditions, results remained unchanged.

Conclusion

There is high prevalence of common and uncommon inflammatory conditions in individuals with high CRP concentrations. Higher CRP concentrations should be interpreted with caution in cardiovascular disease risk assessment.