Seppo Lehto

MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION

BACKGROUND Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of coronary heart disease. It has been debated whether patients with diabetes who have not had myocardial infarctions should be treated as aggressively for cardiovascular risk factors as patients who have had myocardial infarctions. METHODS To address this issue, we compared the seven-year incidence of myocardial infarction (fatal and nonfatal) among 1373 nondiabetic subjects with the incidence among 1059 diabetic subjects, all from a Finnish population-based study. RESULTS The seven-year incidence rates of myocardial infarction in nondiabetic subjects with and without prior myocardial infarction at base line were 18.8 percent and 3.5 percent, respectively (P<0.001). The seven-year incidence rates of myocardial infarction in diabetic subjects with and without prior myocardial infarction at base line were 45.0 percent and 20.2 percent, respectively (P<0.001). The hazard ratio for death from coronary heart disease for diabetic subjects without prior myocardial infarction as compared with nondiabetic subjects with prior myocardial infarction was not significantly different from 1.0 (hazard ratio, 1.4; 95 percent confidence interval, 0.7 to 2.6) after adjustment for age and sex, suggesting similar risks of infarction in the two groups. After further adjustment for total cholesterol, hypertension, and smoking, this hazard ratio remained close to 1.0 (hazard ratio, 1.2; 95 percent confidence interval, 0.6 to 2.4). CONCLUSIONS Our data suggest that diabetic patients without previous myocardial infarction have as high a risk of myocardial infarction as nondiabetic patients with previous myocardial infarction. These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as in nondiabetic patients with prior myocardial infarction.

Impact of Diabetes on Mortality After the First Myocardial Infarction

OBJECTIVE To study diabetic and nondiabetic patients with their first myocardial infarction to determine overall 1-year mortality, out-of-hospital mortality, 28-day mortality of hospitalized patients, and 1-year mortality of 28-day survivors. RESEARCH DESIGN AND METHODS This study—based on the FINMONICA Myocardial Infarction Register, a part of the Finnish contribution to the WHO MONICA Project (World Health Organization Multinational Monitoring of Trends and Determinants of Cardiovascular Disease)—covered coronary heart disease (CHD) deaths and acute CHD events occurring during hospitalization among residents of Finland aged 25–64 years in three geographically defined areas. The study population comprised 620 diabetic and 3,445 nondiabetic patients who had their first myocardial infarction during the years 1988–1992. RESULTS The age- and area-adjusted mortality rates and hazard ratios (HRs) for diabetic versus nondiabetic patients (95% CI) were as follows: The 1-year mortality rate was 44.2% in diabetic men and 32.6% in nondiabetic men (HR, 1.38; 1.18−1.61) and 36.9% in diabetic women and 20.2% in nondiabetic women (HR, 1.86; 1.40−2.46); the out-of-hospital mortality rate was 28.3% in diabetic men and 22.4% in nondiabetic men (HR, 1.25; 1.03−1.52) and 10.4% in diabetic women and 11.0% in nondiabetic women (HR, 0.95; 0.58−1.54); the 28-day mortality rate of hospitalized patients was 14.4% in diabetic men and 8.8% in nondiabetic men (HR, 1.58; 1.15−2.18) and 21.7% in diabetic women and 7.8% in nondiabetic women (HR, 2.60; 1.71−3.95); and the 1-year mortality rate of 28-day survivors was 9.6% in diabetic men and 5.0% in nondiabetic men (HR, 1.97; 1.25−3.12) and 10.7% in diabetic women and 2.5% in nondiabetic women (HR, 4.17; 2.05−8.51). CONCLUSIONS The high mortality rate of diabetic patients after their first myocardial infarction and the high proportion of out-of-hospital deaths in this group imply that vigorous primary and secondary preventive measures should become an integral part of their medical care.

Medial Artery Calcification A Neglected Harbinger of Cardiovascular Complications in Non–Insulin-Dependent Diabetes Mellitus

Medial artery calcification (MAC) is a nonobstructive condition leading to reduced arterial compliance that is commonly considered as a nonsignificant finding. The aim of our study was to investigate the predictive value of MAC in relation to 7-year cardiovascular mortality, coronary heart disease (CHD) events, stroke, and lower extremity amputation in 1059 patients (581 men and 478 women) with non-insulin-dependent diabetes mellitus (NIDDM). At baseline radiologically detectable MAC in femoral arteries was found in 439 patients (41.5%) and intimal-type calcification in 310 diabetic patients (29.3%). The mean fasting plasma glucose at baseline was somewhat higher in women and the duration of diabetes somewhat longer in patients with MAC than in those without, but otherwise the presence of MAC was unrelated to conventional cardiovascular risk factors. During the follow-up 305 diabetic patients died: 208 from cardiovascular disease, 158 from CHD, and 34 from stroke. Furthermore, 58 NIDDM patients underwent their first lower extremity amputation. MAC was a strong independent predictor of total (risk factor-adjusted odds ratio and 95% confidence interval: 1.6; 1.2, 2.2), cardiovascular (1.6; 1.1, 2.2), and CHD (1.5; 1.0, 2.2) mortality, and it was also a significant predictor of future CHD events (fatal or nonfatal myocardial infarction), stroke, and amputation. This relationship was observed regardless of glycemic control and known duration of NIDDM. MAC is a strong marker of future cardiovascular events in NIDDM unrelated to cardiovascular risk factors, supporting the hypothesis that reduced arterial elasticity could lead to clinical manifestations of diabetic macroangiopathy.

EUROASPIRE IV : a European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries

Aims To determine whether the Joint European Societies guidelines on cardiovascular prevention are being followed in everyday clinical practice of secondary prevention and to describe the lifestyle, risk factor and therapeutic management of coronary patients across Europe. Methods and results EUROASPIRE IV was a cross-sectional study undertaken at 78 centres from 24 European countries. Patients <80 years with coronary disease who had coronary artery bypass graft, percutaneous coronary intervention or an acute coronary syndrome were identified from hospital records and interviewed and examined ≥ 6 months later. A total of 16,426 medical records were reviewed and 7998 patients (24.4% females) interviewed. At interview, 16.0% of patients smoked cigarettes, and 48.6% of those smoking at the time of the event were persistent smokers. Little or no physical activity was reported by 59.9%; 37.6% were obese (BMI ≥ 30 kg/m2) and 58.2% centrally obese (waist circumference ≥ 102 cm in men or ≥88 cm in women); 42.7% had blood pressure ≥ 140/90 mmHg (≥140/80 in people with diabetes); 80.5% had low-density lipoprotein cholesterol ≥ 1.8 mmol/l and 26.8% reported having diabetes. Cardioprotective medication was: anti-platelets 93.8%; beta-blockers 82.6%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75.1%; and statins 85.7%. Of the patients 50.7% were advised to participate in a cardiac rehabilitation programme and 81.3% of those advised attended at least one-half of the sessions. Conclusion A large majority of coronary patients do not achieve the guideline standards for secondary prevention with high prevalences of persistent smoking, unhealthy diets, physical inactivity and consequently most patients are overweight or obese with a high prevalence of diabetes. Risk factor control is inadequate despite high reported use of medications and there are large variations in secondary prevention practice between centres. Less than one-half of the coronary patients access cardiac prevention and rehabilitation programmes. All coronary and vascular patients require a modern preventive cardiology programme, appropriately adapted to medical and cultural settings in each country, to achieve healthier lifestyles, better risk factor control and adherence with cardioprotective medications.

Serum Uric Acid Is a Strong Predictor of Stroke in Patients With Non–Insulin-Dependent Diabetes Mellitus

BACKGROUND AND PURPOSE Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased risk for stroke. Hyperuricemia is a common finding in NIDDM, but its significance as an independent risk factor for cardiovascular disease has remained uncertain. Therefore, we investigated serum urate as a predictor of stroke in NIDDM patients free of clinical nephropathy (ie, with a serum creatinine level of < or = 120 micromol/L). METHODS In this population-based study, cardiovascular risk factors were determined in 1017 patients (551 men and 466 women) with NIDDM, aged 45 to 64 years at baseline. The patients were followed up for 7 years with respect to stroke events. RESULTS During the follow-up period, 31 NIDDM patients (12 men [2.2%] and 19 women [4.1%]) died from stroke and 114 NIDDM patients (55 men [10.0%] and 59 women [12.7%]) had a fatal or nonfatal stroke. The incidence of stroke increased significantly by quartiles of serum uric acid levels (P<.001). High uric acid level (above the median value of > 295 micromol/L) was significantly associated with the risk of fatal and nonfatal stroke by Cox regression analysis (hazard ratio, 1.93 [1.30 to 2.86]; P=.001). This association remained statistically significant even after adjustment for all cardiovascular risk factors (hazard ratio, 1.91 [1.24 to 2.94]; P=.003). CONCLUSIONS Our results indicate that hyperuricemia is a strong predictor of stroke events in middle-aged patients with NIDDM independently of other cardiovascular risk factors.

Lipids and Lipoproteins Predicting Coronary Heart Disease Mortality and Morbidity in Patients With Non-insulin-dependent Diabetes

BACKGROUND The aim of this study was to investigate the association of lipoprotein fractions with the future risk of coronary heart disease (CHD) in patients with non-insulin-dependent diabetes (NIDDM). METHODS AND RESULTS At baseline, lipoprotein fractions were determined in 313 diabetic patients with NIDDM (153 men and 160 women), and these patients were followed up for 7 years with respect to CHD events (CHD death or all CHD events including CHD death or nonfatal myocardial infarction). Altogether, 56 NIDDM patients (28 men and 28 women) died from CHD and 25 had a nonfatal myocardial infarction (17 men and 8 women) during the follow-up. NIDDM patients having these CHD events during the follow-up had higher levels of total and very-low-density lipoprotein (VLDL) triglycerides and VLDL cholesterol and lower levels of high-density lipoprotein (HDL) and HDL2 cholesterol than those without CHD events. The risk for CHD death was fourfold and for all CHD events, twofold higher among diabetics with low HDL cholesterol ( or = 0.9 mmol/L. High triglyceride level (> 2.3 mmol/L) was associated with a twofold increase in the risk of CHD events. In multiple logistic regression analyses, HDL was inversely associated with CHD events and VLDL triglycerides with CHD events in NIDDM patients with low HDL cholesterol level ( CONCLUSIONS Our 7-year follow-up study gives evidence that low HDL and HDL2 cholesterol, high VLDL cholesterol, and high total and VLDL triglycerides are powerful risk indicators for CHD events in patients with NIDDM:

Proteinuria Predicts Stroke and Other Atherosclerotic Vascular Disease Events in Nondiabetic and Non–Insulin-Dependent Diabetic Subjects

BACKGROUND AND PURPOSE Increased urinary albumin and protein excretion is associated with cardiovascular disease mortality independent of other cardiovascular risk factors in subjects with non-insulin-dependent diabetes mellitus (NIDDM). We assessed the relationship between the different degrees of proteinuria at baseline and the incidence of stroke, as well as other atherosclerotic vascular disease events, in a prospective study of nondiabetic and NIDDM subjects. METHODS Our study was based on the 7-year follow-up of cohorts of nondiabetic (n = 1375) and NIDDM (n = 1056) subjects in Finland. The urinary protein concentration at baseline was stratified into three categories: no proteinuria (< 150 mg/L), borderline (150 to 300 mg/L), and clinical proteinuria (> 300 mg/L). RESULTS The association between the different degrees of proteinuria and the atherosclerotic vascular events was similar in nondiabetic and NIDDM subjects. Cardiovascular disease mortality was higher both in nondiabetic and NIDDM subjects with clinical proteinuria than in those without proteinuria. The incidence of stroke was 1.6% in nondiabetic subjects without proteinuria, 3.2% in subjects with borderline proteinuria, and 8.5% in subjects with clinical proteinuria (P < .001 for trend). In NIDDM patients, the corresponding rates were 7.2%, 11.1%, and 23.0%, respectively (P < .001 for trend). The association between clinical proteinuria and the incidence of stroke remained significant both in nondiabetic and in NIDDM subjects after adjustment for other cardiovascular risk factors. Clinical proteinuria was also associated with the incidence of coronary heart disease events and that of lower-extremity amputation. NIDDM independently increased the risk of atherosclerotic vascular disease events regardless of the proteinuria status. CONCLUSIONS Clinical proteinuria significantly predicted stroke and other atherosclerotic vascular disease events independent of other cardiovascular risk factors. This finding is compatible with the view that increased urinary protein excretion rate may be associated with widespread vascular damage.

Relationship of Socioeconomic Status to the Incidence and Prehospital, 28-Day, and 1-Year Mortality Rates of Acute Coronary Events in the FINMONICA Myocardial Infarction Register Study

BACKGROUND Low socioeconomic status (SES) is associated with increased coronary heart disease mortality rates. There are, however, very little data on the relation of SES to the incidence, recurrence, and prognosis of myocardial infarction (MI) events. METHODS AND RESULTS The FINMONICA MI Register recorded detailed information on all MI events among men and women aged 35 to 64 years in 3 areas of Finland during the period of 1983 to 1992. We carried out a record linkage of the MI register data with files of Statistics Finland to obtain information on indicators of SES, such as taxable income and education, for each individual who is registered. In the analyses, income was grouped into 3 categories (low, middle, and high), and education was grouped into 2 categories (basic and secondary or higher). Among men with their first MI event (n=6485), the adjusted incidence rate ratios were 1.67 (95% CI 1.57 to 1.78) and 1.84 (95% CI 1.73 to 1.95) in the low- and middle-income categories compared with the high-income category. For 28-day mortality rates, the corresponding rate ratios were 3.18 (95% CI 2.82 to 3.58) and 2.33 (95% CI 2.03 to 2.68). Significant differentials were observed for prehospital mortality rates, and they remained similar up to 1 year after the MI. Findings among the women were consistent with those among the men. CONCLUSIONS The excess coronary heart disease mortality and morbidity rates among persons with low SES are considerable in Finland. To bring the mortality rates of low- and middle-SES groups down to the level of that of the high-SES group constitutes a major public health challenge.

Cardiovascular risk factors clustering with endogenous hyperinsulinaemia predict death from coronary heart disease in patients with Type II diabetes

Aims/hypothesis. Information on the association of hyperinsulinaemia with coronary heart disease (CHD) in patients with Type II (non-insulin-dependent) diabetes is limited and controversial. Therefore, we carried out a prospective study to examine the predictive value of fasting plasma insulin and “hyperinsulinaemia cluster” with regard to the risk of CHD mortality.¶Methods. At baseline risk factors for CHD were determined in 902 patients aged 45 to 64 years with Type II diabetes not treated by insulin (499 men and 403 women). These patients were followed up to 7 years for CHD mortality.¶Results. Coronary heart disease mortality (16.2 % in men, 9.2 % in women) increased significantly in men with increasing plasma insulin tertiles (p = 0.006) and in both sexes combined (p = 0.010) but not in women (p = 0.090). The predictive value of hyperinsulinaemia with regard to death from CHD was independent of conventional cardiovascular risk factors but not of risk factors clustering with hyperinsulinaemia. By applying factor analysis and principal component analysis we showed that “hyperinsulinaemia cluster” (a factor having high positive loadings for body mass index, triglycerides and insulin; and a high negative loading for high-density lipoprotein cholesterol) was predictive of death from CHD in patients with Type II diabetes (hazard ratio with 95 % confidence intervals 1.43 (1.18, 1.73), p < 0.001).¶Conclusion/interpretation. Our results support the notion that cardiovascular risk factors clustering with endogenous hyperinsulinaemia increase the risk of death from CHD in patients with Type II diabetes not treated with insulin. [Diabetologia (2000) 43: 148–155]

Risk Factors Predicting Lower Extremity Amputations in Patients With NIDDM

OBJECTIVE To examine the predictors of lower extremity amputation in patients with NIDDM. RESEARCH DESIGN AND METHODS At baseline, risk factors for amputation were determined in 1,044 NIDDM patients (571 men, 473 women) aged 45 to 64 years. These patients were followed up to 7 years with respect to amputation. RESULTS The incidence of amputation was 5.6% in men and 5.3% in women. High fasting plasma glucose at baseline examination and the duration of diabetes were associated with a twofold risk for amputation. Similarly, glycemic control measured at baseline by HbA1 was an important predictor of amputation. There was a dose-response relationship between plasma glucose or HbA1 and the risk for amputation. The effect of hyperglycemia on the risk of amputation was seen clearly even after the adjustment for other cardiovascular risk factors. Signs of peripheral neuropathy and bilateral absence of Achilles tendon reflexes and vibration sense were important predictors for amputation. Furthermore, absent peripheral artery pulses and femoral artery bruit on auscultation predicted amputation. CONCLUSIONS Our 7-year follow-up study gives strong evidence that poor glycemic control is an important predictor of amputation in patients with NIDDM in addition to clinically detectable peripheral arterial disease and peripheral neuropathy.