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Mitochondrial dysfunction in cardiovascular disease.

Whereas the pathogenesis of atherosclerosis has been intensively studied and described, the underlying events that initiate cardiovascular disease are not yet fully understood. A substantial number of studies suggest that altered levels of oxidative and nitrosoxidative stress within the cardiovascular environment are essential in the development of cardiovascular disease; however, the impact of such changes on the subcellular or organellar components and their functions that are relevant to cardiovascular disease inception are less understood. In this regard, studies are beginning to show that mitochondria not only appear susceptible to damage mediated by increased oxidative and nitrosoxidative stress, but also play significant roles in the regulation of cardiovascular cell function. In addition, accumulating evidence suggests that a common theme among cardiovascular disease development and cardiovascular disease risk factors is increased mitochondrial damage and dysfunction. This review discusses aspects relating mitochondrial damage and function to cardiovascular disease risk factors and disease development.

Animals↗

Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease.

BACKGROUND: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. OBJECTIVE: Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. DESIGN: This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate. RESULTS: Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. CONCLUSIONS: The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

Adult↗

Prevention of cancer and cardiovascular diseases: a common strategy?

Cancer and cardiovascular diseases are two pathological states involving uncontrolled proliferation of either tumor or vascular smooth muscle cells. Interestingly, both types of disease can be prevented by the same type of chemical agent, such as marine polyunsaturated fatty acids, sulfur-containing compounds present in garlic, and wine polyphenols, among others, which seem to be fairly effective in the prevention of certain types of cancer and cardiovascular diseases. This is supported by numerous epidemiological studies and laboratory experiments involving animal models. It is therefore suggested that the mode of action of these compounds interfering with the development of these pathological states share some common trends. This could be taken into consideration in future studies related to the molecular mechanisms leading to these diseases as well as with the chemopreventive potential of some dietary components.

Cardiovascular Diseases↗

Vascular reactivity in young adults and cardiovascular disease. A prospective study.

Cardiovascular reactivity in response to the cold pressor test has been associated with an increased risk of coronary heart disease in middle-aged men. We studied 905 white male medical students, median age 22 years, in the Johns Hopkins Precursors Study. Systolic blood pressure, systolic blood pressure change during the cold pressor test, smoking, cholesterol, Quetelet index, and family history of coronary heart disease were measured on enrollment during 1948-1964. Incidence of cardiovascular morbidity and mortality was ascertained by annual questionnaires and death certificates. There was no association between change in systolic blood pressure during the cold pressor test, whether examined as a continuous variable or a 20 mm Hg or more rise, and the risk of subsequent cardiovascular disease or coronary heart disease. These findings did not change after adjustment for cardiovascular disease risk factors. Previously reported associations may have been due to preexisting arteriosclerosis, which increases the rise in systolic blood pressure during the cold pressor test. We conclude that cardiovascular reactivity to the cold pressor test in young adulthood is not a strong predictor of future cardiovascular disease.

Adult↗

Hyperinsulinemia does not increase the risk of fatal cardiovascular disease in elderly men or women without diabetes: the Rancho Bernardo Study, 1984-1991.

The relation of fasting and 2-hour serum insulin to the risk for fatal cardiovascular disease was examined in men and women without diabetes. Between 1984 and 1987, 80% of all surviving local members of the Rancho Bernardo Study cohort had measures of insulin and glucose levels obtained before and after a 75-g oral glucose tolerance test. Over the next 5 years, there were 24 cardiovascular disease deaths among 538 men and 21 cardiovascular disease deaths among 705 women. Fasting insulin was unrelated to cardiovascular disease death in men or women; 2-hour insulin was significantly lower in men (but not in women) who died from cardiovascular disease. In men, a 1-standard deviation increase in 2-hour insulin was associated with a 36% reduction in cardiovascular disease mortality (p = 0.01). The significant inverse association of 2-hour insulin with cardiovascular disease death persisted in multiply adjusted models (relative hazard = 0.68; 95% confidence interval 0.47-0.96). Patterns were similar when the analysis was repeated, including men with non-insulin-dependent diabetes mellitus or heart disease at baseline. These findings were not explained by antihypertensive drug use or cigarette smoking. Hyperinsulinemia was not a risk factor for cardiovascular disease in these older men or women. The role of insulin as a cardiovascular disease risk factor requires further investigation.

Age Factors↗

Control of hypertension in patients at high risk of cardiovascular disease.

BACKGROUND: Hypertension is a major cardiovascular risk factor, but knowledge about the real magnitude of the problem and its determinants is lacking. AIM: To assess control of hypertension and evaluate medical resource use, in patients at high risk of cardiovascular disease. DESIGN: Multicentric cross-sectional study. METHODS: We collected data for 2205 adult patients from 36 centres, representative of all regions of Spain. Patients had attended out-patient clinics from July 2002 to August 2003, had an absolute cardiovascular risk > or =20% at 10 years (according to the Framingham guidelines), and had a diagnosis of hypertension. Pregnant and terminally ill patients were excluded. RESULTS: Hypertension was inadequately controlled in 1384 patients (62.8%). LDL cholesterol was higher in patients with uncontrolled hypertension (median 130.2 vs. 120.0 mg/dl, p < 0.001). Haemoglobin A(1c) in diabetic patients was also greater in those with uncontrolled hypertension (median 7.10% vs. 6.90%, p = 0.010). Uncontrolled hypertension was associated with the following variables, in descending strength of association: higher LDL cholesterol, taking antihypertensive medication, living in non-metropolitan areas, and higher body mass index. DISCUSSION: Hypertension is poorly controlled in most patients with a high risk of cardiovascular disease. Uncontrolled hypertension is frequently associated with poor control of other risk factors.

Aged↗

Cardiovascular disease in the aged: overview of an autopsy series.

As an overview of cardiovascular disease in the aged, 3657 autopsy cases were analyzed for the frequency and age-wise incidence of cardiovascular disease. The three major categories, ischemic heart disease, valvular heart disease, and aortic aneurysm and dissection were described. 1. The incidence of overall cardiovascular disease increases sharply between the ages of 60 and 75. Prevention and treatment could be effectively directed at this age group. 2. The incidence of organic cardiovascular disease was: myocardial infarction 19.8 percent; valvular disease 10.0 percent; arteriosclerosis obliterans 3.5 percent; aortic aneurysm and dissection 3.3 percent; pericarditis 2.1 percent; cardiomyopathy 1.6 percent; cor pulmonale 1.4 percent; congenital heart disease 0.7 percent; and others 0.8 percent. 3. As coronary sclerosis progresses, death from ischemic heart disease increases; however, 7 out of 10 patients with 3 vessel disease still die of causes other than ischemic heart disease (pneumonia, malignancy etc.). The general management of infection and malignant neoplasms is important in addition to treatment of cardiovascular disease. 4. Except for mitral stenosis, valvular heart disease, the etiology of which is mostly non-rheumatic, increases with advancing age. 5. In aortic aneurysm, the rupture rate is relatively high in the thoracic aorta; however, this may be caused by the successful surgical repair of abdominal aneurysms. An aneurysm below 6 cm in diameter is not absolutely safe from rupture. 6. In aortic dissection, the interval from onset to the death of the patient is often too short to consider surgery.

Age Factors↗

[Cholesterolemia control in Spain, 2000: a tool for cardiovascular disease prevention].

The document "Cholesterolemia control in Spain, 2000: a tool for cardiovascular disease prevention" reviews the current evidence on cardiovascular disease prevention and the therapeutic advances achieved in recent years, in order to aid risk-based clinical decision-making. Cardiovascular diseases rank as the first cause of death in Spain. Their demographic, health and social impact is increasing and it is likely to continue to do so in the next decades. Appropriate treatment for high blood cholesterol and other major risk factors is crucial in cardiovascular disease prevention. Individual risk stratification is essential to determine follow-up periodicity and treatment. Priorities for the control of cholesterolemia and the consequent cardiovascular risk are based on risk stratification. In primary prevention, the therapeutic objective in high risk patients has been established as LDL-cholesterol < 130 mg/dl. In secondary prevention, drug treatment is indicated when LDL-cholesterol > or = 130 mg/dl and the therapeutic objective is LDL-cholesterol < 100 mg/dl. Statins are first line drugs for treatment of high blood cholesterol. In moderate-severe hypertriglyceridemia or low HDL-cholesterol, fibrates are preferred. In acute coronary syndrome, hypolipemiant treatment, should be started as soon as possible, when indicated. Secondary prevention programmes that continually provide good clinical and risk factor control should be provided to coronary heart disease patients.

Adult↗

Cardiovascular disease mortality trends and related risk factors in Canada.

Large declines have occurred in cardiovascular disease mortality in both sexes in Canada during the past two decades. However, there are many countries with substantially lower rates at the present time. Ischemic heart disease mortality accounts for about 60% of cardiovascular disease mortality. Cardiovascular disease rates have declined progressively since the mid-1960s in males 35 to 64 and 65 or more years of age, as well as in females in the latter age group. In younger females, 35 to 64 years of age, a slowly progressive reduction in rates started as early as 1930. Trends for stroke mortality also reveal similar long term reductions in rates since 1930 in both sexes. Relative risks for smoking, hypertension, elevated serum cholesterol and diabetes were analyzed. Almost one-third of the cardiovascular deaths in males were attributable to smoking. Population attributable risks for the four risk factors together were 53% for both sexes. Attention is drawn to the increased risks for persons in lower socioeconomic groups and those with low standards of education and the importance of recognition of these factors in intervention programs.

Adult↗

[Epidemiology of comorbid mental disorders in rehabilitation patients with musculosceletal and cardiovascular diseases].

An association between mental disorders, musculoskeletal and cardiovascular diseases has been reported in many clinical studies with inpatients. However, no data exist about the prevalence of mental disorders in patients undergoing rehabilitation treatment for musculoskeletal and cardiovascular diseases. The present study investigates 4-week, 12-month and lifetime prevalence rates of comorbid mental disorders in more than 1700 patients out of 10 rehabilitation clinics. The patients were screened (GHQ-12, HADS) in the context of a two-stage epidemiological survey. In the second-stage examination a subsample of 369 patients was interviewed with a standardized clinical interview (CIDI) in order to obtain DSM-IV and ICD-10 diagnoses of mental disorders. 43 % (musculoskeletal) and 36 % (cardiovascular) of the patients have high GHQ-scores (cut off > 4). Furthermore, up to 24 % of the musculoskeletal and cardiovascular patients have elevated scores on the HADS subscales depression and anxiety (cut off > 10). For the 4-week period, prevalence rates of mental disorders in the sample of patients with musculoskeletal diseases are 31 % and 20 % in the sample of patients with cardiovascular diseases. The most frequent current disorders are affective and anxiety disorders. The high psychosocial burden expressed by the patients and the prevalence of depressive and anxiety disorders emphasize the importance of (1) effective diagnostic strategies to recognize mental disorders, (2) specialized psychological services in rehabilitation clinics, which provide psychological support and effective interventions for patients with musculoskeletal and cardiovascular diseases.

Adult↗

Cardiovascular disease prevention practices by U.S. Physicians for patients with diabetes.

OBJECTIVE: Cardiovascular diseases account for the majority of morbidity and mortality in patients with type 2 diabetes mellitus. We describe patterns of cardiovascular disease primary prevention practices used for patients with diabetes by U.S. office-based physicians. MEASUREMENTS AND MAIN RESULTS: We analyzed a representative sample of 14,038 visits from the 1995 and 1996 National Ambulatory Medical Care Surveys (NAMCS), including 1,489 visits by patients with diabetes. Physicians completed visit forms describing diagnoses, demographics, services provided, and current medications. Diabetes was defined by diagnostic codes; patients with ischemic heart disease or younger than 30 years were excluded. We estimated national visit volumes by extrapolation using NAMCS sampling weights. Independent determinants of prevention practices were evaluated using multiple logistic regression. Actual visits sampled translated into an estimated 407 million office visits in 1995 and 1996, of which 44.8 million (11%) were by patients with diabetes. Overall, patients with diabetes received more cardiovascular disease prevention services than patients without diabetes, including cholesterol reduction (8% vs 5%, P <.001) and exercise counseling (22% vs 13%, P <.001), blood pressure measurement (82% vs 72%, P <.001), and aspirin prescription (5% vs 2%, P <.001). Patients with diabetes and hyperlipidemia were more likely to receive lipid-lowering medications than patients without these diagnoses (67% vs 51%, P =.007), but those who had diabetes and hypertension or who smoked were no more likely than those without to receive antihypertensive medications or smoking cessation counseling, respectively. These effects persisted in multiple logistic regression analyses controlling for potential confounders. CONCLUSIONS: Patients with diabetes visiting U.S. physicians in 1995 and 1996 received somewhat more cardiovascular disease prevention services than patients without diabetes. Absolute rates of services, however, remained lower than desired based on national recommendations. Current evidence suggests that wider implementation of these recommendations can be expected to reduce the burden of cardiovascular disease in patients with diabetes.

Adult↗

Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease.

BACKGROUND: Glucocorticoids have adverse systemic effects, including obesity, hypertension, and hyperglycemia, that may predispose to cardiovascular disease. The effect of glucocorticoid use on cardiovascular disease has not been quantified. OBJECTIVE: To test the hypothesis that users of exogenous glucocorticoids have an increased risk for cardiovascular disease. DESIGN: A cohort study using a record linkage database. SETTING: Tayside, Scotland, United Kingdom. PATIENTS: 68,781 glucocorticoid users and 82,202 nonusers without previous hospitalization for cardiovascular disease who were studied between 1993 and 1996. MEASUREMENTS: The average daily dose of glucocorticoid exposure during follow-up was categorized as low (inhaled, nasal, and topical only), medium (oral, rectal, or parenteral <7.5 mg of prednisolone equivalent), or high (> or =7.5 mg of prednisolone equivalent). Poisson regression model, sensitivity analysis, and propensity score methods were used to investigate the association between glucocorticoid exposure and cardiovascular outcome. RESULTS: 4383 cardiovascular events occurred in 257,487 person-years of follow-up for a rate of 17.0 (95% CI, 16.5 to 17.5) per 1000 person-years in the comparator group, and 5068 events occurred in 212,287 person-years for a rate of 23.9 (CI, 23.2 to 24.5) per 1000 person-years in the group exposed to glucocorticoids (22.1, 27.2, and 76.5 in low, medium, and high groups, respectively). The absolute risk difference was 6.9 (CI, 6.0 to 7.7) per 1000 person-years (5.1, 10.1, and 59.4, respectively). After adjustment for known covariates, the relative risk for a cardiovascular event in patients receiving high-dose glucocorticoids was 2.56 (CI, 2.18 to 2.99). LIMITATIONS: Because the data were observational, residual confounding cannot be excluded. CONCLUSION: Treatment with high-dose glucocorticoids seemed to be associated with increased risk for cardiovascular disease.

Cardiovascular Diseases↗

Ultrasound assessment of subclinical cardiovascular disease in a community-based multiethnic population and comparison to the Framingham score.

The presence of subclinical cardiovascular disease has been documented to indicate high coronary risk. This study investigated the impact of subclinical cardiovascular disease derived from echocardiography and carotid ultrasonography on traditional coronary risk stratification using the Framingham risk score (FRS) in a community-based, multiethnic population. Echocardiography and carotid ultrasonography were performed in 1,445 subjects (aged >39 years; 40% men; 53% Hispanic, 20% white, 24% black) from the Northern Manhattan Study. Subclinical cardiovascular disease was defined as the presence of left ventricular hypertrophy and/or carotid plaque greater than the gender-specific 75th percentile of the left ventricular mass index and maximal carotid plaque thickness distribution. The prevalence of subclinical cardiovascular disease was examined in each FRS category (low, intermediate, and high risk). In subjects with low or intermediate FRSs, 35% had subclinical cardiovascular disease (low FRS 29%, intermediate FRS 42%). In the intermediate FRS category, subclinical cardiovascular disease was significantly more prevalent in women than in men (53% vs 32%, p <0.0001) and in black and white subjects than in Hispanics (59% and 46% vs 33%, p <0.0001 and p = 0.040, respectively). In conclusion, the ultrasound assessment of subclinical cardiovascular disease may help reclassify 1/3 of subjects with low or intermediate FRSs into higher risk groups. In the intermediate FRS category, FRS appears to underestimate the coronary risk more in women than in men and more in whites and especially in blacks than in Hispanics.

Aged↗

A comparison of the associations between risk factors and cardiovascular disease in Asia and Australasia.

BACKGROUND: Cardiovascular disease is already the leading cause of death in many Asian populations. Relationships between vascular risk factors and cardiovascular disease may differ in Asian and western populations. Previously, a lack of prospective data has prevented the reliable quantification of such differences, which, if they were shown to exist, would suggest that novel cardiovascular prevention and treatment strategies are required for Asia. DESIGN: An individual participant data meta-analysis of 32 studies from the Asia-Pacific region involving 331 100 subjects (75% from Asia; 25% from the predominantly Caucasian populations of Australia and New Zealand). METHODS: Outcomes were death from coronary heart disease, ischaemic and haemorrhagic stroke. Hazard ratios were estimated from Cox models for systolic blood pressure (SBP), total cholesterol, triglycerides, body mass index, diabetes and current cigarette smoking, stratified by study and sex and adjusted for age, the other risk factors and regression dilution. RESULTS: After an average period of follow-up of 4 years there were 2082 deaths from coronary heart disease, 600 from haemorrhagic stroke and 420 from ischaemic stroke. The direction and strength of the associations between risk factors and cardiovascular outcomes were similar in the two regions, although in two cases there were significant differences. Triglycerides were more strongly associated with coronary heart disease in Australia and New Zealand (P = 0.03), whereas SBP showed a stronger relationship with haemorrhagic stroke in Asia (P = 0.04). CONCLUSIONS: Classical vascular risk factors act similarly in Asian and Caucasian populations; prevention and treatment strategies should thus be similar. Blood pressure reduction should be particularly effective in Asia.

Asia↗

C-reactive protein: associations with haematological variables, cardiovascular risk factors and prevalent cardiovascular disease.

C-reactive protein (CRP) has been proposed as a risk factor for cardiovascular disease; however, this association is confounded by mutual relationships with both classical and haematological cardiovascular risk factors. We, therefore, measured CRP with a high-sensitivity assay in stored plasma samples from 414 men and 515 women in the north Glasgow MONICA (MONItoring trends in CArdiovascular diseases) survey, to study its correlation with haematological variables, classical risk factors and prevalent cardiovascular disease. CRP correlated with age, oral contraceptive use, menopause and most classical cardiovascular risk factors (except blood pressure). CRP also correlated with plasma levels of the pro-inflammatory cytokine interleukin 6, and haematocrit, viscosity, red cell aggregation, white cell count, and coagulation factors [fibrinogen, factor (F) VII in women, FVIII, FIX] and inhibitors (antithrombin and protein C in women; protein S) but not coagulation activation markers. CRP was significantly associated with prevalent cardiovascular disease in both men (P = 0.03) and women (P = 0.009), however, the association became non-significant after adjustment for firstly classical risk factors, then fibrinogen. We conclude that correlations with classical and haematological risk factors account for a substantial component of the association of CRP with prevalent cardiovascular disease, but there is evidence of a residual, independent effect among women.

Adult↗

Familial clustering of cardiovascular disease in patients with insulin-dependent diabetes and nephropathy.

BACKGROUND: Patients who have insulin-dependent diabetes mellitus and nephropathy have an excess of cardiovascular disease. Familial factors may in part account for this phenomenon. METHODS: We identified 61 white patients under 65 years of age with insulin-dependent diabetes who had nephropathy, and then matched them with 61 diabetic patients without nephropathy. We determined the prevalence of cardiovascular disease in the parents of these patients with use of information obtained from death certificates or from the World Health Organization questionnaire for cardiovascular disease. RESULTS: The rates of ascertainment of information were 96 percent (n = 117) for the parents of diabetic patients with nephropathy and 95 percent (n = 116) for the parents of patients without nephropathy. Cardiovascular disease was more often a direct cause of death among the parents of diabetic patients with nephropathy (40 percent vs. 22 percent, P less than 0.03), and the combined morbidity and mortality from cardiovascular disease in this group was greater than that in the parents of diabetic patients without nephropathy (31 percent vs. 14 percent, P less than 0.01). The age-adjusted and sex-adjusted relative risk of cardiovascular disease in this group of parents was 2.9 (95 percent confidence interval, 1.5 to 5.5; P less than 0.001). Moreover, a paternal history of cardiovascular disease was associated with a significantly increased risk of nephropathy in the diabetic patient after the analysis was adjusted for age, sex, and duration of diabetes (odds ratio, 3.2; 95 percent confidence interval, 1.3 to 7.9; P less than 0.01). Among the diabetic patients with nephropathy, those who had had a cardiovascular event were much more likely to have a family history of cardiovascular disease (odds ratio, 6.2; 95 percent confidence interval, 2.0 to 19.0; P less than 0.005) than those who had not had such an event. CONCLUSIONS: Among patients with insulin-dependent diabetes, a parental history of cardiovascular disease is significantly associated with the development of nephropathy and, among those with nephropathy, increases the likelihood of cardiovascular disease.

Adolescent↗

Cardiovascular disease and risk of Alzheimer's disease.

Several recent studies demonstrate associations between cardiovascular disease and its risk factors and the incidence of Alzheimer's disease. This review will examine the evidence for these associations and possible pathogenetic pathways. Clinical relevance and implications of these associations will also be discussed.

Aging↗

Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.

BACKGROUND: Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. METHODS: The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. RESULTS: The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79). CONCLUSIONS: A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.

Amputation, Surgical↗