Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction

Haffner, Steven M.; Lehto, Seppo; Rönnemaa, Tapani; Pyörälà, Kalevi; Laakso, Markku

doi:10.1056/nejm199807233390404

Cited by 6,191 publications

(3,828 citation statements)

References 17 publications

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“…Individuals with diabetes mellitus are at high risk of coronary heart disease (CHD), and when they experience a clinical CHD event they have a worse prognosis than individuals without diabetes mellitus 1, 2, 3, 4, 5. Therefore, prevention of CHD is essential for this population 1, 3, 5, 6.…”

Section: Introductionmentioning

confidence: 99%

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Race‐Sex Differences in Statin Use and Low‐Density Lipoprotein Cholesterol Control Among People With Diabetes Mellitus in the Reasons for Geographic and Racial Differences in Stroke Study

Gamboa

Colantonio

Brown

et al. 2017

JAHA

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BackgroundStatin therapy is a cornerstone of cardiovascular disease risk reduction for people with diabetes mellitus. Past reports have shown race‐sex differences in statin use in general populations, but statin patterns by race and sex in those with diabetes mellitus have not been thoroughly studied.Methods and ResultsOur sample of 4288 adults ≥45 years of age with diagnosed diabetes mellitus who had low‐density lipoprotein cholesterol (LDL‐C) >100 mg/dL or were taking statins recruited for the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2007. Exposures included race‐sex groups (white men [WM], black men [BM], white women [WW], black women [BW]) and factors that may influence healthcare utilization. Proportions and prevalence ratios were calculated for statin use and LDL‐C control. Statin use for WM, BM, WW, and BW was 66.0%, 57.8%, 55.0%, and 53.6%, respectively (P<0.001). After adjustment for healthcare utilization factors, statin use was lower for BM, WW, and BW compared with WM (prevalence ratios [95%CI]: 0.96 [0.89‐1.03], 0.86 [0.80‐0.92], and 0.87 [0.81‐0.93], respectively, P<0.001). LDL‐C control among those taking statins for WM, BM, WW, and BW was 75.3%, 62.7%, 69.0%, and 56.0%, respectively (P<0.001). After adjustment, LDL‐C control was lower for BM, WW, and BW compared with WM (prevalence ratios [95%CI]: 0.85 [0.79‐0.93], 0.89 [0.82‐0.96], and 0.73 [0.67‐0.80], respectively, P<0.001).ConclusionsRace‐sex disparities in statin use and LDL‐C control were only partly explained by factors influencing health services utilization. Healthcare provider awareness of these disparities may help to close the observed race‐sex gaps in statin use and LDL‐C control among people with diabetes mellitus.

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Section: Introductionmentioning

confidence: 99%

“…Therefore, prevention of CHD is essential for this population 1, 3, 5, 6. Major risk factors including dyslipidemia are common among individuals with diabetes mellitus 7.…”

Section: Introductionmentioning

confidence: 99%

Race‐Sex Differences in Statin Use and Low‐Density Lipoprotein Cholesterol Control Among People With Diabetes Mellitus in the Reasons for Geographic and Racial Differences in Stroke Study

Gamboa

Colantonio

Brown

et al. 2017

JAHA

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“…Prolongation of the QT interval and increased dispersion of repolarization have been observed in the diabetic population,4, 5, 6, 7, 8, 9, 10 and these variables, together with intervening comorbidities,11 represent critical substrates for the occurrence of electrical disturbances 4, 12, 13, 14, 15, 16, 17. But whether alterations at the cellular level contribute to protracted electrical recovery and repolarization variability with diabetes remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Meo

Meste

Signore

et al. 2016

JAHA

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BackgroundDiabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat‐to‐beat variability of repolarization.Methods and ResultsDiabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single‐cell patch‐clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ‐treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat‐to‐beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K+ and L‐type Ca2+ currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes.ConclusionsReductions in the repolarizing K+ currents may contribute to electrical disturbances of the diabetic heart.

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“…Patients with diabetes mellitus have dyslipidemia and metabolic complications that contribute to an increased risk of cardiovascular disease (CVD) 1, 2, 3, 4, 5, 6. Statin therapy is the recommended first‐line therapeutic approach for lipid management of high‐risk patients; however, many patients with diabetic dyslipidemia do not achieve adequate low‐density lipoprotein (LDL) cholesterol (LDL‐C) lowering on statin monotherapy 7, 8, 9, 10, 11.…”

Section: Introductionmentioning

confidence: 99%

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

Tomassini

Tershakovec

et al. 2015

JAHA

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BackgroundPatients with diabetes mellitus and cardiovascular disease may not achieve adequate low‐density lipoprotein cholesterol (LDL‐C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL‐C–lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL‐C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose‐doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low‐ and high‐density lipoprotein particle number and lipoprotein‐associated phospholipase A2 [Lp‐PLA2]) was assessed.Methods and ResultsTreatment effects on low‐ and high‐density lipoprotein particle number (by NMR) and Lp‐PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low‐density lipoprotein‐particle number numerically more than did statin dose‐doubling and was comparable with R10 (−133.3, −94.4, and −56.3 nmol/L, respectively; P>0.05). Increases in high‐density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose‐doubling (1.5 and −0.5 μmol/L; P<0.05) and comparable with R10 (0.7 μmol/L; P>0.05). Percentages of patients attaining low‐density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose‐doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp‐PLA2 activity significantly more than did statin dose‐doubling (−28.0 versus −3.8 nmol/min per mL, P<0.05) and was comparable with R10 (−28.0 versus −18.6 nmol/min per mL; P>0.05); effects on Lp‐PLA2 concentration were modest.ConclusionsIn diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp‐PLA2 activity more than did statin dose‐doubling and was comparable with R10, consistent with its lipid effects.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.

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Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction

Cited by 6,191 publications

References 17 publications

Race‐Sex Differences in Statin Use and Low‐Density Lipoprotein Cholesterol Control Among People With Diabetes Mellitus in the Reasons for Geographic and Racial Differences in Stroke Study

Race‐Sex Differences in Statin Use and Low‐Density Lipoprotein Cholesterol Control Among People With Diabetes Mellitus in the Reasons for Geographic and Racial Differences in Stroke Study

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

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