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PubMed1998

Do known cardiovascular risk factors mediate the effect of alcohol on cardiovascular disease?

The association between alcohol intake and atherosclerotic cardiovascular disease (CVD) in epidemiological studies is consistent and shows some protection from CVD at consumption levels of one to two drinks per day, but a sharp increase in CVD associated with three or more drinks per day. Analyses of potential mediators of effects of alcohol on CVD show that it increases high density lipoprotein (HDL) cholesterol levels and favourably influences thrombotic factors, especially fibrinogen, and also fibrinolytic factors. Some evidence also suggests moderate alcohol consumption may reduce insulin resistance. However, studies also show an adverse effect of alcohol, particularly at higher doses, on blood pressure (leading to hypertension) and directly on the myocardium (leading to arrhythmias and myocardiopathy). Statistical modelling of the alcohol-CVD relationship is consistent in several studies, with a protective pathway via elevated HDL cholesterol and an adverse pathway through elevated blood pressure. Other possible mediators influenced by alcohol have not yet been examined in this type of analysis. The French Paradox has led to speculation that wine is the only protective alcoholic beverage for CVD, or at least that it has a stronger effect. Multiple non-ethanol components of wine have been studied in the laboratory and have been shown to have antioxidant or anticoagulant effects. Although wine does appear more protective in ecological studies, studies within cohorts show similar effects across alcoholic beverages, suggesting confounding in ecological studies by diet, lifestyle, or other variables. The key component of alcoholic beverages thus appears to be ethanol, consistent with the known potent effects of ethanol on HDL cholesterol and thrombotic factors. The upswing in CVD risk with three or more drinks per day is sharp and emphasizes that benefit from alcohol is limited to moderate consumption only. This upswing also cautions against any public health recommendation to drink alcohol, since many persons will not or cannot limit their intake to moderate levels.

Alcohol Drinking↗
PubMed1994

Intranasal delivery of cardiovascular agents: an innovative approach to cardiovascular pharmacotherapy.

The intranasal administration of drugs has long been used for the topical treatment of various nasal disorders. Many features of the intranasal mucosa also make it useful for delivery of systemically active agents. It has been shown that intranasal drug administration can provide plasma drug levels similar to those observed with comparable doses of parenteral drugs. The feasibility of intranasal administration of propranolol, nifedipine, and nitroglycerin has been investigated in several small clinical studies. Intranasal propranolol has been shown to improve exercise tolerance in patients with angina pectoris. Intranasal nifedipine has been used to treat patients with perioperative hypertension and hypertensive crisis. Intranasal administration of nitroglycerin was shown to blunt the hypertensive response to endotracheal intubation. These studies and others suggest that intranasal delivery of cardiovascular drug treatment could be used in those clinical situations where a rapid or intermittent drug effect is desired and can potentially serve as an alternative to parenteral drug administration.

Absorption↗
PubMed1996

Cardiovascular risk factors in Norwegian women using oral contraceptives: results from a cardiovascular health screening 1985-88.

We analyzed data from 4,905 women aged 20-39 and 14,803 aged 40-49 who attended a health survey in Norway 1985-88, to study cardiovascular risk factors in users of oral contraceptives, all types and specifically by formulation. In age group 20-39, users of low-dose estrogen/ progestin regimens were younger, had lower body mass index (BMI), less often reported coronary heart disease in relatives, and less often used saturated fat on bread than did non-users. In age group 40-49, smoking was more prevalent in users of low-dose estrogen/progestin than in non-users. In both age groups the mean ratio of total/HDL cholesterol, the mean level of non-fasting triglycerides, and the mean systolic and diastolic blood pressures were higher in oral contraceptive users than in non-users. Among the users, a more favorable pattern was found in women using progestin-only oral contraceptives, as blood pressure levels were equal to those of non-users and total cholesterol and triglycerides were both 0.1-0.2 mmol/l below the non-users, in both age groups. However, users of low-dose estrogen formulations containing desogestrel 0.15 mg, norethisterone (norethindrone) 0.5 mg or lynestrenol 2.5 mg had the highest levels of HDL, even higher than the non-users. A pattern of higher triglycerides and higher ratio of total/ HDL cholesterol was found in smokers, compared with non-smokers, among users of any type of contraceptives, and in non-users.

Adult↗
PubMed1993

Use of nonionic or low osmolar contrast agents in cardiovascular procedures. American College of Cardiology Cardiovascular Imaging Committee.

Low osmolar contrast agents produce less adverse electrophysiologic and hemodynamic alterations during cardiac catheterization. The nonionic agents probably reduce the risk of provoking myocardial ischemia during coronary arteriography or ventriculography. Patients also report less subjective sensation of discomfort during administration of low osmolar agents for cardiovascular procedures. However, nonionic agents have not been proved to reduce the incidence of several serious complications of cardiac catheterization, including acute renal failure and anaphylactoid reaction. Although evidence is inconclusive, there may be an increased risk of thromboembolic complications during cardiac catheterization when certain low osmolar nonionic agents are administered. Nonionic contrast agents have not been definitely proved to reduce the risk of death after cardiac catheterization.

Cardiac Catheterization↗
PubMed2006

Increased targeting of cardiovascular risk factors in patients with chronic kidney disease does not improve atheroma burden or cardiovascular function.

BACKGROUND: Although multiple risk factor intervention (MRFI) is recommended to reduce the increased morbidity and mortality of cardiovascular disease (CVD) in chronic kidney disease (CKD), its efficacy is unknown. We studied the efficacy of a MRFI program in CKD. METHODS: This randomized controlled study of 200 patients with stage 4 or 5 CKD compared a physician-supervised, nurse-driven MRFI clinic (focused on dyslipidemia, hyperhomocysteinemia, blood pressure [BP], anemia, and hyperphosphatemia) with conventional care in CKD. One hundred eleven subjects completed 2 years of follow-up (median follow-up 674 days [interquartile range {IQR} 348-719 days]). Outcome measures were atheroma burden (carotid intimamedia thickness [IMT]) and endothelial function (brachial artery reactivity [BAR]). RESULTS: The MRFI group showed significant improvements, compared with usual care, in serum low-density lipoprotein cholesterol (-30.9 mg/dL vs -12.7 mg/dL, P = .001), homocysteine (-6.95 vs -0.67 micromol/L, P < .001), systolic BP (-6.9 vs -0.2 mm Hg, P = .049), and diastolic BP (-4.8 vs -1.0 mm of Hg, P = .043). No significant changes were seen in serum phosphate or hemoglobin level. Despite observed improvements in risk factors, no differences from baseline were demonstrated for IMT (-0.00 vs -0.01 mm, P = .533) or BAR (0.09% vs 0.22%, P = .834). Forty-two patients reached a composite end point of CVD death, acute coronary syndrome, revascularization, nonfatal stroke, and amputation and this was similar between groups (23 vs 19 events, P = .475). CONCLUSIONS: A MRFI program was not associated with improvement in vascular structure or function in stage 4 or 5 patients with CKD.

Adult↗
PubMed2004

Impact of age on cardiovascular risk: implications for cardiovascular disease management.

Cardiovascular disease (CVD) represents a major global healthcare problem. The prevalence of this condition increases with age. As many countries around the world are experiencing an increase in the proportion of elderly people in the population, this raises serious issues for cardiac and cerebrovascular disease prevention and management. A wealth of data has established smoking, dyslipidemia, hypertension and type 2 diabetes as major risk factors for cardiac and cerebrovascular events. This article reviews the evidence that links these metabolic risk factors with an increased risk of complications, and assesses the data concerning how risk changes with age. This review also focuses on how these conditions can be optimally managed and whether treatment outcomes are affected by age. The current status of research is assessed and issues which remain to be resolved are highlighted.

Age Factors↗
PubMed2005

Cardiovascular reactivity: mechanisms and pathways to cardiovascular disease.

Researchers in physiology, psychology, and medicine have held the idea that risk for cardiovascular disease is increased by exaggerated responses to stress. Some epidemiological evidence supports this view and shows that exaggerated blood pressure responses to stress add to disease prediction beyond that provided by standard risk factors. Most studies of reactivity and disease risk have taken a correlational approach to the reactivity-disease relationship. This paper presents a model of central nervous system control over peripheral response systems that provides a way of designating three sources of exaggerated stress reactivity that may vary across individuals. The top level in the model consists of the limbic system and prefrontal cortex as interacting areas that form psychological stress responses. These frontal-limbic interactions are a means of translating experiential and affective processes into bodily responses. The middle level consists of hypothalamus and brainstem areas that translate descending influences into bodily outputs. Activation levels in these structures can lead to enhanced reactivity to many forms of challenge. The final level consists of the peripheral effectors that create the response itself; altered effector function can be a source of enhanced reactivity. Study designs that involve both psychological and physiological challenges and that take account of self-reports of affect and activation provide a basis for separating these sources of responsivity. This organization may provide useful insights into the sources of stress reactivity that characterize specific groups at risk and allow inferences as to the source of the disease pathophysiology.

Animals↗
PubMedDate not supplied

The association between educational level and risk of cardiovascular disease fatality among women with cardiovascular disease.

BACKGROUND: The inverse relation of socioeconomic status with incident cardiovascular diseases (CVDs) has been well established. However, few data are available describing this relation among ethnically diverse women with prevalent CVD. Using education as a proxy for socioeconomic status, we examined its relation to CVD mortality among women with established CVD. SUBJECTS: Data from 2,157 women with CVD at baseline, who participated in nine long-term U.S. cohort studies, were pooled. METHODS: Cox regression models adjusted for history of diabetes mellitus, total cholesterol, systolic and diastolic blood pressure, body mass index, smoking, race/ethnicity, and age at baseline were used to estimate hazard ratios for CVD mortality between non-high school graduates and high school graduates. RESULTS: During a mean follow-up time of 11.5 years, 615 CVD deaths were observed. There was an age-dependent (p = .003) inverse association between education and CVD mortality among women with CVD. At age 60, the risk of dying due to CVD among non-high school graduates was more than twice greater than that of high school graduates (hazard ratio = 2.34; 95% CI 1.27-4.29). At age 65, the hazard ratio decreased to 1.31 (95% CI 1.00-1.71). By age 70, there was no difference in the hazard of dying between high school graduates and nongraduates (hazard ratio = 1.01; 95% CI .85-1.21). CONCLUSIONS: Our results show that among women with CVD, educational level was a significant, and age-dependent, predictor of fatal CVD independent of other traditional risk factors. These women are an important high-risk population to target secondary prevention and educational efforts.

Adult↗
PubMed1997

Negative association between reported life events and cardiovascular disease risk factors in employed men: the CORDIS Study. Cardiovascular Occupational Risk Factors Determination in Israel.

There is evidence of a link between stressful life events and risk of cardiovascular disease, but the pathway has not been fully explored. The present study of 1859 employed men tested the association between reported intensity of life events and blood pressure and serum lipid levels, risk behaviors, and psychological distress symptoms. The findings revealed a striking disparity in the outcomes. Life events were negatively associated with systolic (p = 0.001) and diastolic (p = 0.038) blood pressure, triglycerides (p = 0.011), and uric acid (p = 0.05), even after controlling for job strain and other possible confounders. In contrast, life events were positively associated with somatic complaints (p < 0.0001), anxiety (p < 0.0001), irritability (p < 0.0001), and depression (p < 0.0001). In addition there was a linear trend between intensity level of life events and low exercise (p = 0.006), smoking (p = 0.007), and alcoholic intake (p = 0.035). The possibility that the above disparity is a product of powerful biases, such as repressive coping and negative affectivity disposition, is discussed.

Adult↗
PubMed2005

Cardiovascular risks in type 2 diabetes and secondary cardiovascular prevention.

In order to emphasize the necessity of treating aggressively the main cardiovascular risk factors (hypertension, hypercholesterolemia, smoking) in diabetics, it was proposed in 1998 to assimilate their absolute risk level to that of non diabetics with a history of myocardial infarction. In this short review, it is recalled that diabetics (and coronary patients as well) constitute heterogeneous groups and the results of such comparisons depend heavily on the selection of the two groups as shown by published works on this topic since 1998. Anyway, the treatment of the main risk factors in true diabetics should be strict and new preventive approaches by treating the disease itself are awaited.

Cardiovascular Diseases↗
PubMed2002

[Cardiovascular system of normal aged subjects. Cardiovascular senescence].

The cardiovascular system of the elderly is characterised by (i) an increased characteristic impedance of the big vessels, without hypertension; (ii) a cardiac index unchanged at rest and during submaximal exercising, despite a diminished VO2 max; (iii) a diastolic dysfunction with reduced rapid early filling (E wave at echo) and enhanced atrial systole (A wave); (iv) benign arrhythmias; (v) a reduced coronary reserve and an increased sensitivity to ischemia; (vi) an efficacy of converting enzyme inhibitors remaining unchanged, despite an altered renin-agiotensin system.

Aged↗
PubMed1999

Influence of pattern of drinking on cardiovascular disease and cardiovascular risk factors--a review.

There is an established inverse relationship between the regular light consumption of alcohol (5-10 g/day) and the incidence of coronary artery disease (CAD). This association has several biologically plausible mechanisms with dose-dependent effects of alcohol to increase HDL cholesterol, lower plasma fibrinogen and inhibit platelet aggregation. However, such a protective effect against atheroma cannot be considered in isolation from known adverse effects on blood pressure and triglycerides or possible detrimental effects of episodic or binge drinking on several other cardiovascular end-points and risk factors. In subjects with pre-existing CAD, an alcoholic binge can increase both silent myocardial ischaemia and angina. During withdrawal following binge drinking, marked fluctuations in blood pressure together with heightened platelet activation and adverse changes in the balance of fibrinolytic factors, may offer an explanation for the reported association between episodic heavy drinking and ischaemic stroke. This has been seen particularly in young males and extends further to an increase in both subarachnoid haemorrhage and intracerebral haemorrhage after binge drinking. Intervention studies in man have shown acute increases in blood pressure in men who drink predominantly at weekends, compared to longer-term pressor effects in regular daily drinkers. We have been unable, however, to reproduce the finding of unfavourable effects of binge drinking on the lipid profile that have been reported in animal studies and man. Binge drinking may also induce cerebrovascular spasm or cause both ventricular and supraventricular arrhythmias, especially atrial fibrillation. Alcohol-induced arrhythmia has been postulated as the basis for alcohol-related sudden coronary death in those subjects with pre-existing CAD. Hence, further exploration of any protective association of alcohol against CAD needs to carefully consider the implications of pattern of drinking for the relationship. The modulating influences of co-timing of drinking with meals, cigarette smoking or illicit drug use also need to be evaluated. Without such vital information, public health advice on alcohol and CAD will be limited in its scope and potentially flawed in its impact.

Alcohol Drinking↗
PubMedDate not supplied

Is aspirin "the weakest link" in cardiovascular prophylaxis? The surprising lack of evidence supporting the use of aspirin for cardiovascular disease.

It is currently fashionable to prescribe aspirin, long-term to people with or at high risk of vascular events due to atherosclerosis. There is a moderately conclusive evidence for a short-term benefit after an acute vascular event. However, there is remarkably little evidence that long-term aspirin is effective for the prevention of vascular events and managing side effects may be expensive. Reductions in nonfatal vascular events may reflect an ability of aspirin to alter cosmetically the presentation of disease without exerting real benefit. Cardiovascular medicine appears prone to fads and fashions that are poorly substantiated by evidence. The current fashion for prescribing aspirin is reminiscent of the now discredited practice of widespread prescription of class I anti-arrhythmic drugs for ventricular ectopics. We should learn from experience.

Aspirin↗
PubMed2001

Efficacy of atorvastatin in achieving National Cholesterol Education Program low-density lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH).

BACKGROUND: Recent studies have demonstrated that women at high risk for cardiovascular disease (CVD) benefit from cholesterol lowering to an extent similar to that of men. The ability to achieve established treatment goals for low-density lipoprotein cholesterol (LDL-C) in women with clearly defined risk factors has not been examined in detail. METHODS AND RESULTS: We have determined the efficacy and frequency of achieving target levels for LDL-C with atorvastatin on the basis of National Cholesterol Education Program Adult Treatment Panel II recommendations in 318 women according to the presence of CVD (198 women) or risk factors for CVD (120 women) and the presence of mixed dyslipidemia with obesity with or without CVD (72 women). Mean baseline LDL-C concentrations for women with established CVD were in the upper 10% of the distribution for age-matched North American women and, for those without CVD, were also extremely elevated and were in the top 5% of the LDL-C distribution for age-matched women in this population. The majority of participants without CVD (63%) reached LDL-C targets (LDL-C or=2 CVD risk factors) with 10 mg atorvastatin and 79% reached targets with up to 20 mg of atorvastatin. For women with established CVD, 34% achieved an LDL-C <or=100 mg/dL (2.6 mmol/L) with 10 mg and 60% reached this target with up to 20 mg of atorvastatin. With maximal titration to the LDL-C target, up to and including 80 mg atorvastatin, 87% of women without CVD and 80% of women with established CVD achieved LDL-C targets. The presence of mixed dyslipidemia with obesity did not affect the frequency of achieving LDL-C targets. CONCLUSION: Atorvastatin is very effective in achieving National Cholesterol Education Program Adult Treatment Panel II target concentrations for LDL-C in the majority of women with established CVD or CVD risk factors.

Adult↗
PubMed2003

Secondary prevention of renal and cardiovascular disease: results of a renal and cardiovascular treatment program in an Australian aboriginal community.

Australian Aborigines are experiencing an epidemic of renal and cardiovascular disease. In late 1995 we introduced a treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated ESRD of 2760 per million. Eligible for treatment were people with hypertension, diabetics with micro or overt albuminuria, and all people with overt albuminuria. Treatment centered around use of perindopril (Coversyl, Servier), with other agents added to reach BP goals; attempts to control glucose and lipid levels; and health education. Thirty percent of the adult population, or 267 people, were enrolled, with a mean follow up of 3.39 yr. Clinical parameters were followed every 6 mo, and rates of terminal endpoints were compared with those of 327 historical controls matched for baseline disease severity, followed in the pretreatment program era. There was a dramatic reduction in BP in the treatment group, which was sustained through 3 yr of treatment. Albuminuria and GFR stabilized or improved. Rates of natural deaths were reduced by an estimated 50% (P = 0.012); renal deaths were reduced by 57% (P = 0.038); and nonrenal deaths by 46% (P = 0.085). Survival benefit was suggested at all levels of overt albuminuria, and regardless of diabetes status, baseline BP, or prior administration of angiotensin converting enzyme inhibitors (ACEI). No significant benefit was apparent among people without overt albuminuria, nor among those with GFR less than 60 ml/min. An estimated 13 renal deaths and 10 nonrenal deaths were prevented, with the number-needed-to-treat to avoid one terminal event of only 11.6. Falling deaths and renal failure in the whole community support these estimates. The program was extremely cost-effective. Programs like this should be introduced to all high-risk communities as a matter of urgency.

Adolescent↗
PubMed2006

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors.

BACKGROUND: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. METHODS: In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. RESULTS: Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). CONCLUSION: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.

Adult↗
PubMed2004

Intensive lifestyle modification: impact on cardiovascular disease risk factors in subjects with and without clinical cardiovascular disease.

Intensive lifestyle modification programs are intended to stabilize or promote regression of coronary artery disease; however, clinical response is often nonuniform, complicating appropriate utilization of resources and prediction of outcome. This study assessed physiological and psychological benefits to 72 persons participating in a prospective, nonrandomized, four-component lifestyle change program and compared response between patients with clinical cardiovascular disease (CVD) and patients with elevated risk factors for CVD but without clinical manifestations of disease. Subjects entering the program due to elevated risk factor levels alone demonstrated equal or greater benefit, in terms of improvement in primary CVD risk factors and reduction in measures of coronary disease risk developed in the Framingham Heart Study, than those with clinical CVD. These findings suggest that intensive lifestyle change programs may be important for primary prevention in individuals at increased risk of CVD.

Adult↗
PubMed2005

Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort.

OBJECTIVES: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer's disease (AD). DESIGN: Longitudinal cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Men and women (N=3,602) with a brain magnetic resonance imaging (MRI) scan but no dementia were followed for 5.4 years. Participants with stroke were excluded. MEASUREMENTS: Neurologists and psychiatrists classified incident cases of dementia and subtype using neuropsychological tests, examination, medical records and informant interviews. CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race, sex, education, Mini-Mental State Examination score, and income were assessed as potential confounders. RESULTS: The incidence of dementia was higher in those with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was 34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per 1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95% confidence interval (CI)=1.0-1.7). Rates of AD were highest in those with PAD (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95% CI=1.4-4.2). Results were similar with further exclusion of those with vascular dementia from the AD group. A gradient of increasing risk was noted with the extent of vascular disease. CONCLUSION: Older adults with CVD other than stroke had a higher risk of dementia and AD than did those without CVD. The risk was highest in people with PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for AD.

Aged↗