History Of Cardiovascular Disease Events Research Articles

Early and Intensive Therapy for Management of Hyperglycemia and Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Background Type 2 diabetes mellitus (T2DM) results in significant morbidity and mortality. Results of recent randomized controlled trials demonstrated the ability of early and intensive therapy to reduce the risk of microvascular complications. However, controversy surrounds the ability of such therapy to reduce the risk for macrovascular complications. Objectives This article reviews results from recent clinical trials in patients with T2DM as well as extended follow-up of earlier trials to determine if early, intensive, and individualized therapy aimed at the underlying pathogenesis of the disease could decrease the risk for long-term complications, including cardiovascular disease (CVD). Methods Information was obtained by a search of the PUBMED and EMBASE databases using the search terms type 2 diabetes mellitus, glycosylated hemoglobin, pathophysiology of type 2 diabetes, glycemic control, early intervention, multifactorial intervention, cardiovascular disease, β-cell function, and antidiabetes therapy for the period between 1995 and 2010. Articles dealing with outcomes trials, impact of therapy on microvascular and macrovascular complications, effects of therapeutic agents on the pathophysiology of T2DM, and the impact of agents on CV risk factors were then preferentially selected for in-depth review. Results Large-scale clinical trials in patients with T2DM, although largely negative at 5 years for macrovascular end points, suggested benefit for patients with a shorter duration of T2DM (ie, <10 years) and still supported a treatment strategy of early, intensive, and individualized therapy to prevent long-term complications of the disease. In Steno-2, after 13 years of follow-up, early, intensive, multifactorial therapy was associated with a 56% lower risk of all-cause death ( P = 0.02) and a 57% lower risk of death from CVD ( P = 0.04). In the 10-year follow-up to the United Kingdom Prospective Diabetes Study, intensive therapy was associated with a significant 15% reduction in the risk of myocardial infarction ( P = 0.01) and a significant 13% reduction in the risk of death from any cause ( P = 0.007). Therapy should be aimed at correcting underlying pathophysiologic defects, including β-cell failure and insulin resistance, and should also correct underlying risk factors for CVD whenever possible. Conclusions Early and intensive antidiabetes treatment was recommended in patients with T2DM, particularly those with a shorter duration of disease and without a history of CVD. The goal was to safely lower glycosylated hemoglobin to <7%, therefore providing beneficial effects on the risk for complications. Hypoglycemia should be avoided. In addition, less aggressive treatment might be suitable for older patients with longstanding diabetes and a history of CVD events. Clinical trial results also provided support for a second important aspect of individualized treatment for patients with T2DM—multifactorial intervention aimed at controlling CVD risk factors.

Rest/Activity Rhythms and Cardiovascular Disease in Older Men

Prior studies have suggested an increased risk of cardiovascular disease (CVD)-related mortality in older adults with disturbed circadian rest/activity rhythms (RARs). The objective goal of this study was to examine the association between disrupted RARs and risk of CVD events in older men. A total of 2968 men aged 67 yrs and older wore wrist actigraphs for 115 ± 18 consecutive hours. RAR parameters were computed from wrist actigraphy data and expressed as quartiles (Q). CVD events consisted of a composite outcome of coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD) events. Secondary analyses examined associations between RARs and individual components of the composite outcome (CHD, stroke, and PVD). There were 490 CVD events over an average of 4.0 ± 1.2 yrs. Overall, reduced amplitude (HR = 1.31, 95% confidence interval [CI] 1.01–1.71 for Q2 vs. Q4) and greater minimum (HR = 1.33, 95% CI 1.01–1.73 for Q4 vs. Q1) were associated with an increased risk of CVD events in multivariable-adjusted models. In secondary analyses, there was an independent association between reduced amplitude (HR = 1.36, 95% CI 1.00–1.86) and greater minimum activity counts (HR = 1.39, 95% CI 1.02–1.91) with increased risk of CHD events. Reduced F value (HR = 2.88, 95% CI 1.41–5.87 for Q1 vs. Q4 and HR = 2.71, 95% CI 1.34–5.48 for Q2 vs. Q4) and later occurring acrophase of the RAR (HR = 1.65, 95% CI 1.04–2.63 for Q4 vs. Q2–3) were associated with an increased risk of PVD events. Results were similar in men without a history of CVD events. The findings revealed that among older men, measures of decreased circadian activity rhythm robustness (reduced amplitude and greater minimum activity) were associated with an increased risk of CVD events, primarily through increased risk of CHD or stroke events, whereas measures of reduced circadian activity rhythmicity were not associated with risk of CVD events overall, but were associated with an increased risk of PVD events. These results should be confirmed in other populations. (Author correspondence: E-mail: ames0047@umn.edu)

Hostility and Platelet Reactivity in Individuals Without a History of Cardiovascular Disease Events

To examine the association between hostility and platelet reactivity in individuals without a prior history of cardiovascular disease (CVD) events. Hostility is associated with incident CVD events, independent of traditional risk factors. Increased platelet reactivity and thrombus formation over a disrupted coronary plaque are fundamental for CVD event onset. Hypertensive patients (n = 42) without concomitant CVD event history completed the 50-item Cook-Medley Hostility Scale, and a subset score of 27 items (Barefoot Ho) was derived. We examined the relationship between Barefoot Ho scores and platelet aggregation. We also examined individual components of Barefoot Ho (aggressive responding, cynicism, and hostile affect) and their associations with platelet aggregation. Platelet reactivity, induced by adenosine diphosphate (ADP), was assessed by standard light transmission aggregometry, the current gold standard method of platelet aggregation assessment. Barefoot Ho scores were related significantly to increased rate of platelet aggregation in response to ADP. Of the three Barefoot Ho components, only aggressive responding was associated independently with increased platelet aggregation rate. The strength of these relationships did not diminish after adjusting for several standard CVD risk factors. These data demonstrate that hostility, particularly the aggressive responding subtype, is associated with platelet reactivity-a key pathophysiological pathway in the onset of CVD events.

Sodium Intake and Mortality Follow-Up in the Third National Health and Nutrition Examination Survey (NHANES III)

Sodium restriction is commonly recommended as a measure to lower blood pressure and thus reduce cardiovascular disease (CVD) and all-cause mortality. However, some studies have observed higher mortality associated with lower sodium intake. To test the hypothesis that lower sodium is associated with subsequent higher cardiovascular disease (CVD) and all cause mortality in the Third National Health and Nutrition Examination Survey (NHANES III). Observational cohort study of mortality subsequent to a baseline survey. Representative sample (n = 8,699) of non-institutionalized US adults age > or = 30, without history of CVD events, recruited between 1988-1994. Dietary sodium and calorie intakes estimated from a single baseline 24-h dietary recall. Vital status and cause of death were obtained from the National Death Index through the year 2000. Hazard ratio (HR) for CVD mortality of lowest to highest quartile of sodium, adjusted for calories and other CVD risk factors, in a Cox model, was 1.80 (95% CI 1.05, 3.08, p = 0.03). Non-significant trends of an inverse association of continuous sodium (per 1,000 mg) intake with CVD and all-cause mortality were observed with a 99% CI of 0.73, 1.06 (p = 0.07) and 0.86, 1.04 (p = 0.11), respectively, while trends for a direct association were not observed. Observed associations of lower sodium with higher mortality were modest and mostly not statistically significant. However, these findings also suggest that for the general US adult population, higher sodium is unlikely to be independently associated with higher CVD or all-cause mortality.

Cardiovascular disease, mortality, and retinal microvascular characteristics in type 1 diabetes: Wisconsin epidemiologic study of diabetic retinopathy.

Diabetic retinopathy and proteinuria, manifestations of microvascular abnormalities, occur early in the course of diabetes mellitus; in contrast, macrovascular cardiovascular complications usually occur later. Retinal vessel characteristics may be informative about risk of cardiovascular disease in persons with diabetes. We evaluated this in a longitudinal cohort study of persons with type 1 diabetes. The population consisted of persons with type 1 diabetes who were receiving care in 11 counties in Wisconsin. Subjects (n = 996) were examined at baseline (1980-1982), and 4, 10, 14, and 20 years later. Evaluations included medical history and measurements of height, weight, blood pressure, and glycosylated hemoglobin. Fundus photographs were graded for diabetic retinopathy at baseline, and the same photographs were graded later for the diameters of retinal blood vessels. At each examination, a history of cardiovascular disease events since the last examination (and prior to baseline) was obtained. Mortality was monitored yearly. The 20-year age-adjusted cumulative incidences were 18.1% for angina, 14.8% for myocardial infarction, and 5.9% for stroke. Severity of diabetic retinopathy was associated with angina and stroke. Arteriovenous ratio was associated with myocardial infarction. Of 273 deaths, 176 involved heart disease. The severity of retinopathy and arteriovenous ratio was associated with heart disease mortality. Nephropathy was more informative about the cardiovascular end points than were the blood vessel characteristics. Incidences of cardiovascular disease, including mortality, were common in people with type 1 diabetes during a 20-year interval. Retinal vascular characteristics were associated with these end points, but this association was confounded by nephropathy.

Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.

To investigate the screening performance of measuring blood pressure and other variables in identifying those who will develop, or die from, ischaemic heart disease and stroke. To quantify by how much drugs that lower blood pressure will reduce the risk of ischaemic heart disease and stroke in those designated 'screen positive'. MEDLINE, Cochrane collaboration and Web of Science databases; Stroke registries; Health Survey for England; Office of National Statistics; BUPA (British United Provident Association) study. Relevant cohort studies and randomised trials were identified and analysed. Statistical analysis was used to determine drug efficacy and adverse effects. Lowering blood pressure by 5 mmHg diastolic reduces the risk of stroke by an estimated 34% and ischaemic heart disease by 21% from any pre-treatment level; there is no threshold. These estimates, from cohort studies, have been corroborated by the results of randomised trials in persons with high, average and below average levels of blood pressure. In spite of its importance in causing cardiovascular disease blood pressure is a poor predictor of cardiovascular events. Its poor screening performance is illustrated by the findings that in the largest cohort study, persons in the top 10% of the distribution of systolic blood pressure experienced only 21% of all ischaemic heart disease events and 28% of all strokes at a given age. Combining several reversible risk factors adds little to the screening performance of blood pressure alone; for example the 25% of men aged 5564 at highest computed risk (> or =1%) experience only 46% of all ischaemic heart disease events. The main methods of screening should be to identify all persons with a history of cardiovascular disease events (for example identifying patients at the time of hospital discharge following a first myocardial infarction detects 50% of all heart disease deaths in a population at a false positive rate of 12%), and to use a person's age. Identifying everyone with a history of myocardial infarction or stroke in a population and everyone aged 55 or more would include 98% of all deaths from ischaemic heart disease and stroke. The five main categories of blood pressure lowering drugs, thiazides, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists and calcium channel blockers, significantly reduce blood pressure from all pre-treatment levels though the extent of the blood pressure reduction increased with pre-treatment blood pressure. The reductions were similar at standard dose for the five categories; average reduction was 9.1 systolic and 5 diastolic. The effect of combinations of two drugs on blood pressure was additive. No effect of age was apparent, given blood pressure. There were no serious metabolic consequences of using these drugs in standard dose. The evidence presented indicates that three drugs in combination may reduce stroke by about two-thirds and ischaemic heart disease by half. The report suggests that the term hypertension should be avoided because it is not a disease and it implies another category (normotensives) who would not benefit from lowering blood pressure. Blood pressure reduction using combinations of safe, well-established drugs is effective in preventing cardiovascular events. It is therefore suggested that such preventive therapy be considered more widely in people who by virtue of existing disease or simply age are at risk of a heart attack or stroke regardless of initial blood pressure.

Family History Fails to Detect the Majority of Children with High Capillary Blood Total Cholesterol

To examine the predictive value of family history in detecting children with high blood cholesterol, finger-stick screening was done in 1,118 children ages 9-10 whose parents provided parental and grandparental history of cardiovascular disease events and risk factors. Mean blood total cholesterol was 167.7 mg/dl with no significant gender or ethnic differences. Of 157 children with blood cholesterol 200 mg/dl or greater, only 61 (38.9%) had a family history of early myocardial infarction or hyperlipidemia; however, the prevalence of a positive family history varied from 2.8% in Vietnamese-Americans to 38.5% in Spanish-surnamed students to 52.6% in all other children. Adherence to current policies recommending screening only children with a positive family history will result in failing to detect a majority of children whose blood cholesterol levels exceed desirable levels for adults, particularly those from ethnic families recently arrived in the U.S.