Macrovascular Disease

Cardiovascular disease, that includes coronary heart disease (CHD) rebrovascular disease, and peripheral vascular disease, is the leading cause of mortality in people with diabetes. The majority of deaths are due to CHD, where the risk is two- to fourfold greater in patients, especially women with diabetes, when compared with age-matched subjects without diabetes (11). The relative importance of the problem has been highlighted by recent studies. Gu et al. compared adults with diabetes with those without diabetes for time trends in mortality from all causes, heart disease, and ischemic heart disease. They based the data on the First National Health and Nutrition Examination Survey (NHANES) conducted between 1971 and 1975 and the NHANES follow-up conducted between 1982 and 1984. The nondiabetic men had a 36.4% decline in age-adjusted heart disease mortality compared with a 13.1% decline in diabetic men. In the nondiabetic women it declined 27% but in the diabetic women the rate increased 23%. The suggestions for this trend were that risk factors for cardiovascular disease in patients with diabetes may have declined less or the patients with diabetes may have benefited less from improved medical care for heart disease. Another suggestion was that the overall rates of cardiovascular disease could have declined less in those with diabetes (12). Haffner and colleagues compared the mortality from CHD in Finland in a recent paper. They studied 1059 subjects with type 2 diabetes and 1373 nondiabetic subjects with and without previous myocardial infarction (MI) (13). The 7-year incidence rates of MI in the nondiabetic group at baseline were 18.8% and 3.5%, respectively. The 7-year rates of MI in the diabetic subjects at baseline were 45% and 20.2% respectively. Even after adjusting for age, sex, total cholesterol, hypertension, and smoking the risk was similar in both groups. This suggests that patients with type 2 diabetes without a prior MI have the same risk as someone without diabetes and a prior myocardial infarct. This study clearly reveals the enormous risk of heart disease in patients with type 2 diabetes and emphasizes the need for aggressive risk factor treatment. In fact after the first cardiac event, 50% of patients with diabetes die within one year, and half die before they can reach a hospital (14). This very high mortality suggests that a primary prevention strategy is needed to reduce the risk. Multiple studies have now been done that show the benefit of lowering cholesterol and blood pressure in patients with diabetes. The Scandanvian Simvastatin Survival Study (4S) and the Cholesterol and Recurrent Events (CARE) (15,16) both showed a reduction in cardiovascular mortality in small numbers of patients with diabetes that were included in these studies. The 4S was a secondary prevention randomized control trial that reduced CHD death or nonfatal MI. There were 22.9% events in the intervention group compared with 43.8% in the control group. The CARE trial included similar endpoints as well as revascularization, and there were 28.7% events in the intervention group compared to 36.8% in the control group. The Hypertension Optimal Treatment Trial (HOT) and the United Kingdom Prospective Diabetes Study (UKPDS) (17,18) also demonstrated a significant reduction in cardiovascular events as well as a reduction in microvascular events in the UKPDS, with blood pressure control. In the HOT trial there was a 4.4% event rate in the treatment group compared to 9% in the control group. This was a more than 50% reduction with a target diastolic pressure of 80 mmHg. In the UKPDS tight blood pressure control resulted in 14.1% acute myocardial infarction (AMI) events compared to 21.3% in the less-tight control group.

More recent data comes from the Heart Protection Study (HPS) and the Collaborative Atorvastatin Diabetes Study (CARDS). The HPS was a secondary prevention trial with 5,963 patients with diabetes and 14,573 with arterial occulsive disease and no known diabetes. The use of 40 mg of simvastatin resulted in a 22% reduction in first occurrence of any major vascular event in patients on simvastatin treatment and a 27% reduction in participants whose pretreatment LDL cholesterol was below 3.0 mmol (116 mg/dL). Furthermore there was a 25% reduction in other subgroups studied including duration of diabetes, age over 65 years, control of diabetes or presence of hypertension (46).

The CARDS trial is significant because it is a primary prevention trial in 2838 patients with type 2 diabetes with out high-LDL cholesterol levels. At study entry the subjects had not documented previous cardiovascular disease, LDL cholesterol of 4.14 mmol or less, a fasting triglyceride of 6.78 mmol or less and at least one of the following: retinopathy, albuminuria, current smoking, or hypertension. The trial was terminated 2 years earlier as the use of 10 mg of atorvastatin resulted in a 37% reduction in at least one major cardiovascular event over the 3.9 years of the trial. In addition stroke was reduced by 48%.This trial in patients with type 2 diabetes without elevated LDL cholesterol raises the question of whether all patients with type 2 diabetes and one other risk factor should be on statin therapy (47).

In both type 1 and type 2 diabetes accelerated macrovascular disease is a problem and the etiology is multifactorial, with hyperglycemia playing a significant role. In the type 2 patient there are multiple cardiovascular risk factors that form part of the insulin resistance syndrome. There are abnormalities in lipid metabolism, derangements in the coagulation system, the effects of hyperglycemia, and the potential role of hyperinsulinemia. To this list can be added increasing age, the development of obesity, and hypertension. It is beyond the scope of this chapterto review in detail the various abnormalities, but one issue deserves attention and that is the role of hyperglycemia. There is considerable debate in the medical literature on the role of hyperglycemia as an independent risk factor for CHD. Balkau et al. reviewed the question by examining the mortality data from the Paris Prospective Study. This was a study of 7018 men, aged 44 to 55 years who were not known to have diabetes at baseline. They found no clear thresholds for fasting or 2 h glucose concentrations above which, all cause and CHD mortality increased sharply. They did find, that in the upper levels of glucose distributions, the risk for death progressively increased with increasing fasting and 2 h glucose levels (19). A subject with a fasting glucose level of 7.8 mmol/L had a risk of death 40% greater than one with fasting glucose of 6.0 mmol/L. The lowest risk was found in the 4.5 to 5.5 mmol/L range. For the 2 h glucose, a level of 11.1 mmol/L carried a 55% greater risk than for a level of 7.7 mmol/L. The lowest risk was in the 5.5 to 6.5 mmol/L range for the 2 h glucose. After adjustments for other risk factors the 2 h glucose was still significantly associated with both all causes and CHD mortality, whereas the fasting correlated with all causes of death. One limitation of the study is that it is done on men and the relationship of these results to women is unclear at present.

In a metaregression analysis of 20 recent studies involving 95,783, nondiabetic subjects, Coutinho et al. (20) revisit this question. While acknowledging the limitations of the different types of study design, varying methods of glucose measurements, and different glucose loads for the tolerance tests, they did find that a high fasting, 1 and 2 h glucose increased risk for cardiovascular events. A fasting level of 6.1 mmol/L increased the relative risk 1.33 compared with a fasting level of 4.2 mmol/L. Similarly the 2 h glucose of 7.8 mmol/L was associated with a relative risk of 1.58. The DECODE Study included over 25,000 patients with a mean follow-up time was 7.3 years (20a). This study showed that a high blood glucose concentration 2 h after a glucose load was associated with increased risk of death, independently of fasting blood glucose. These studies do not imply a cause and effect relationship, but do suggest that with increasing glucose levels there may be worsening of the underlying risk factors for cardiovascular disease. In patients with impaired glucose tolerance there is an increased risk for cardiovascular disease.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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