Risk Factor Intervention Strategy Research Articles

Cause-specific mortality of 1-year survivors of subarachnoid hemorrhage

To assess long-term, cause-specific mortality rates and rate ratios of the patients alive at 1 year after subarachnoid hemorrhage (SAH). The population-based, prospective, cohort study with a nested case-control design consisted of 64,349 persons (aged 25-74 years at enrollment) who participated in the National FINRISK Study between 1972 and 2007. Four hundred thirty-seven SAH cases, 233 one-year SAH survivors, and their matched intrinsic controls were identified and followed up until the end of 2009 through the nationwide Finnish Causes of Death Register. All-cause mortality rates and rate ratios of the 1-year SAH survivors and controls were the main outcome measures. Eighty-eight (37.8%) of 233 one-year SAH survivors died during the total follow-up time of 2,487 person-years (median 8.6 years, range 0.1-35.8 years). The 1-year SAH survivors had a hazard ratio of 1.96 (95% confidence interval 1.57-2.47) for death compared with the matched general population with 10 controls for each SAH survivor. One-year SAH survivors had up to 31 additional deaths per 1,000 person-years compared with controls with minimal cerebrovascular risk factors. The higher long-term risk of death among SAH survivors was attributed solely to cerebrovascular diseases, and most important modifiable risk factors for death were smoking, high systolic blood pressure (≥ 159 mm Hg), and high cholesterol levels (≥ 7.07 mmol/L). One-year SAH survivors have excess mortality, which is attributed to an exceptional risk of deadly cerebrovascular events. Aggressive post-SAH cerebrovascular risk factor intervention strategies are highly warranted.

Proactive multiple cardiovascular risk factor management compared with usual care in patients with hypertension and additional risk factors: the CRUCIAL trial

Objective:To investigate whether a proactive multifactorial risk factor intervention strategy using single-pill amlodipine/atorvastatin (5/10, 10/10 mg) in addition to other antihypertensive and lipid-lowering therapy, as required, resulted in greater reduction in calculated Framingham 10-year coronary heart disease (CHD) risk compared with usual care (UC) after 52-weeks treatment.Research design and methods:Prospective, multinational, open-label, cluster randomized trial, with the investigator as the unit of randomization. Eligible hypertensive patients were 35–79 years of age, with ≥3 additional cardiovascular risk factors, but no history of CHD and baseline total cholesterol (TC) ≤6.5 mmol/l.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00407537.Main outcome measure:The primary endpoint was calculated Framingham 10-year CHD risk at 52 weeks.Results:Of the 140 randomized sites, 136 sites contributed 1461 patients. Mean baseline age and low-density lipoprotein cholesterol (LDL-C) were comparable between treatment arms. Mean baseline BP (150.3/89.7 vs. 144.3/86.5 mmHg) and Framingham CHD risk (20.0 vs. 18.1%) were higher in the proactive intervention versus the UC arm (p < 0.002 for both). At week 52, mean CHD risk was 12.5% in the proactive intervention arm and 16.3% in the UC arm (p < 0.001). The difference, observed at weeks 16 and 52, was primarily driven by significant differences in systolic BP and in TC between the two arms. Overall, adverse events (AEs) were reported in 48.8% and 44.0% of patients in the proactive intervention and the UC arm, respectively. Although there were differences in the incidence of AEs between the treatment arms, the AE profile in the proactive intervention arm was consistent with previous safety experience for this medication.Conclusions:A proactive multifactorial risk factor intervention strategy that simultaneously treated both BP and cholesterol regardless of individual risk factors per se, is more effective in reducing calculated Framingham 10-year CHD risk than UC in patients with hypertension and additional risk factors.

Clinical Profile of the Adolescent/Adult Fontan Survivor

The study aims to describe the clinical profile of the adult Fontan survivor and identify the worries, symptoms, and the impact of cardiac surveillance most commonly experienced. A descriptive, cross-sectional design was used. The study was performed in outpatient adult and pediatric cardiology clinics in university-affiliated and private practice offices. Fifty-four adolescent and adult patients with single ventricle congenital heart disease who have undergone the Fontan procedure participated in the study. The mean age was 26 ± 9 years with 52% female and 63% Caucasian. Demographic and clinical data were obtained by a standard intake form and retrospective chart reviews. The Congenital Heart Disease TNO/AZL Adult Quality Of Life questionnaire was completed to assess worries, symptoms, and the impact of cardiac surveillance. The majority were single (73%), employed or full-time students (93%), with health insurance (94%), had a single left ventricle (78%), the diagnosis of tricuspid atresia or double inlet left ventricle (59%), lateral tunnel Fontan type (44%), history of arrhythmias (76%), left ventricle ejection fraction percentage >50 (66%), oxygen saturations >90% (70%), frequent headaches (50%), scoliosis (22%), varicose veins, ascites, and liver cirrhosis (46%), normal body mass index (59%), and New York Heart Association class I (48%) and II-III (52%). Primary worries related to current health (83%), job/employment (69%), ability to work, (61%) and living independently (54%). The most bothersome symptoms were shortness of breath with ambulation (69%), dizziness (61%), and palpitations (61%). Fontan survivors experience residua and sequelae from multiple surgical procedures and the natural disease course. Our results support the need for ongoing assessment of both physical symptoms and psychosocial concerns, and suggest the need for multiple risk factor intervention strategies that improve physical and emotional health in Fontan survivors.

Design and Rationale of a Real-Life Study to Compare Treatment Strategies for Cardiovascular Risk Factors: The CRUCIAL Study

The CRUCIAL trial was designed to compare the relative reduction in calculated Framingham coronary heart disease risk when a multiple risk factor intervention strategy, based on single-pill amlodipine besylate/atorvastatin calcium, was compared with a usual-care strategy. Eligible patients had treated or untreated hypertension, ≥ 3 additional cardiovascular risk factors, and baseline total cholesterol ≤ 6.5 mmol/L, but no coronary heart disease. The CRUCIAL trial was a 12-month, international, multicenter, prospective, stratified, cluster-randomized, parallel-design, open-label trial conducted in 20 countries in Asia, the Middle East, Europe, and Latin America. We anticipate the results of this study will be available in mid to late 2010. In this article we report the rationale for and design of the CRUCIAL trial and discuss how the challenges in the design and conduct of this cluster-randomized trial were addressed. The cluster-randomized trial design, with the investigator as the unit of randomization, was chosen to minimize contamination between the trial arms. The intent of the study was to compare the new therapeutic strategy with customary treatment practices, so no recommendation was made regarding the choice of antihypertensive or lipid-lowering drugs in the usual-care arm. It was considered that if the investigator managed both arms of the trial it would be difficult to prevent crossover of treatment strategies. Patients were enrolled in the study before the investigators were randomized to avoid selection bias. Investigators were randomized in a 1:1 ratio within each country to explicitly balance the treatment arms with respect to potential confounding factors. The cluster effect was taken into account in the sample size calculation. The findings from the CRUCIAL trial have the potential to inform current thinking on how to effectively reduce the cardiovascular risk of patients with hypertension and additional risk factors but only modestly elevated total cholesterol.

Correlates of Fatigue in Patients With Heart Failure

This study was conducted to determine the prevalence of fatigue and identify its demographic, clinical, and psychological correlates in 150 heart failure (HF) patients (73% men, 66% Caucasian, mean age 55.0 years, mean ejection fraction 26.7%+/-11%), from a single HF center, using the Profile of Mood States-Fatigue Subscale, the Minnesota Living With Heart Failure Questionnaire, and the Beck Depression Inventory. Sociodemographic and clinical data were obtained through self-report and chart abstraction. High levels of fatigue were reported in 50.4% of men and 51.2% of women. In a multivariate model, maximal workload, physical health, emotional health, and depression explained 51% of the variance in fatigue (P<.001). Fatigue in patients with HF is associated with both clinical and psychosocial variables, offering a number of targets for intervention. These findings suggest the need for multiple risk factor intervention strategies that improve physical and emotional health to decrease fatigue. Patients with depression warrant particular scrutiny.

Dietary fatty acids, hemostasis, and cardiovascular disease risk

The cause of many myocardial infarctions is occlusive thrombosis, or a blood clot that stops blood flow in a coronary artery. Hemostasis involves a complex system of factors, which normally form and degrade blood clots, that work within a delicate balance. Emerging evidence suggests that some hemostatic factors, including factor VII, fibrinogen, and plasminogen activator inhibitor-1, are associated with increased risk for cardiovascular disease (CVD). Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. Dietary supplementation with marine n-3 fatty acids prolongs bleeding time and may decrease risk for thrombosis. Factor VII coagulant activity modestly decreases with reductions in saturated fatty acid (SFA) intake and thereby may contribute to the beneficial effects of low SFA diets. Large triglyceride-rich particles formed during postprandial lipemia can support the assembly and function of coagulation complexes and seem to play a role in the activation of factor VII, and thus may partially explain increased CVD risk associated with increased postprandial triglyceridemia. As our understanding of the role of dietary fatty acids and hemostasis evolves, it is likely that we will be able to make specific dietary recommendations to further decrease CVD risk. At this juncture, however, increasing marine n-3 fatty acids and decreasing certain SFAs are leading strategies to reduce hemostatic CVD risk factors. An array of dietary strategies that target multiple CVD risk factors could have a greater impact on CVD than a single risk factor intervention strategy.

Macrovascular disease in diabetes: current status.

Clearly, macrovascular complications are the prognosis limiting problem of diabetes patients which consecutively account for the majority of socio-economic burden of the disease. The overall morbidity and mortality development does not indicate improvement hallmarking better or at least adequate care for these patients. Possible explanations address the late detection problem of a clinically silent disease onset as well as unrecognised multiple comorbid conditions all of which end-up with endothelial dysfunction as representation of the so called "functional atherosclerosis" and blood hyperresponsiveness. Here, we describe new experimental aspects of the early atherosclerosis development focussing inflammation as one driving pathogenetic force for the evolution of the complicated lesion type in diabetes. However, emphasis is put on the view that inflammation, atherogenesis and thrombogenesis are severely crosslinked by soluble and cellular adhesion molecules. From a diagnostic point of view genomic detection of risk associated genes opens both the vision of early identification of high risk individuals and the targeting of drug intervention based on conditioned responsiveness. By using available drugs and evidence based risk factor intervention strategies a plea is made for a multimodal therapeutic approach fitted to the individual patient's needs aiming at endpoint reduction. This corresponds to the recent releases of guidelines from nearly all vascular medicine related scientific societies. Diabetes is a vascular disease!

Risk profile and health awareness in male offspring of parents with premature coronary heart disease.

The offspring of parents who suffer from premature coronary heart disease have a significantly higher risk of early cardiac death than controls. A genetic predisposition is compounded by a commonality of environmental risk factors within families. Increasing awareness, early detection and modification of risk factors are essential components of an effective public health strategy to protect this highly vulnerable population. The sons (n = 571) of parents with premature coronary heart disease attended the Toronto Rehabilitation Centre for a risk factor evaluation that included an interview with questionnaire, measurement of body dimensions and blood lipids, and cardiopulmonary exercise testing. A follow-up questionnaire was sent out 2 years after the evaluation. Despite concern about family history, 23% of subjects were smokers and 75% were inactive. Objective data confirmed a substantial prevalence of cardiac risk factors: less than optimal cardiovascular fitness (48%), overweight (34%), total cholesterol > or = 200 mg/dL (46%), high-density lipoprotein cholesterol < or = 35 mg/dL (26%), low-density lipoprotein cholesterol > or = 160 mg/dL (16%), triglycerides > or = 200 mg/dL (27%), and lipoprotein (a) > 30 mg/dL (24%). Although almost all had a family physician whom they had seen an average of 1.8 times in the past year, and 4.7 times in the previous 3 years, screening and risk factor intervention strategies were disappointing. Two-year follow-up data showed a heightened health awareness, with a greater proportion of subjects exercising and attempting to maintain an appropriate body mass. The male offspring of parents who have suffered a premature coronary event exhibit a substantial prevalence of modifiable risk factors. The family physician can play an essential role in promoting a healthy lifestyle through risk reduction counselling and screening.

Risk factors for haemorrhagic stroke a case–control study

A hospital based pair-matched case-control study was undertaken to identify risk factors for haemorrhagic stroke. The study took place in the Government Medical College Hospital, Nagpur, India, a tertiary care hospital. The study consisted of 166 hospitalised computerised tomography scan proved cases of haemorrhagic stroke (International Classification Diseases 9, 431-432), and an age and sex matched control per case. The controls were selected from patients who attended the study hospital for conditions other than stroke. The study included hypertension, serum total cholesterol, alcohol intake, smoking, diabetes mellitus, obesity, physical inactivity, type A personality, use of anticoagulants/antiplatelets, family history of stroke, history of cardiac diseases, past history of transient ischaemic attack, history of claudication and oral contraceptive use in women, as risk factors for haemorrhagic stroke. Bivariate analysis included odds ratio (OR), 95% confidence intervals (CI) for OR and McNemar's chi2 test. Multivariate analysis was carried out by conditional multiple logistic regression analysis. Attributable Risk Percent (ARP), Population Attributable Risk Percent (PARP) and their 95% CI were estimated for significant factors. On conditional multiple logistic regression five risk factors-hypertension (OR=1.9, 95% CI 1.5-2.5), serum total cholesterol (OR=2.3, 95% CI 1.4-4.9), use of anticoagulants and antiplatelet agents (OR=3.4, 95% CI 1.1-10.4), past history of transient ischaemic attack (OR=8.4, 95% CI 2.1-33.6) and alcohol intake (OR=2.1, 95% CI 1.3-3.6) were significant. Estimates of ARP and PARP for these factors confirmed their etiological and preventable role respectively. The current study recognised the significance of five risk factors, which are preventable. These risk factors may be considered for devising effective risk factor intervention strategy for haemorrhagic stroke.

Risk factors for haemorrhagic stroke: a case–control study

A hospital based pair-matched case-control study was undertaken to identify risk factors for haemorrhagic stroke. The study took place in the Government Medical College Hospital, Nagpur, India, a tertiary care hospital. The study consisted of 166 hospitalised computerised tomography scan proved cases of haemorrhagic stroke (International Classification Diseases 9, 431–432), and an age and sex matched control per case. The controls were selected from patients who attended the study hospital for conditions other than stroke. The study included hypertension, serum total cholesterol, alcohol intake, smoking, diabetes mellitus, obesity, physical inactivity, type A personality, use of anticoagulants/antiplatelets, family history of stroke, history of cardiac diseases, past history of transient ischaemic attack, history of claudication and oral contraceptive use in women, as risk factors for haemorrhagic stroke. Bivariate analysis included odds ratio (OR), 95% confidence intervals (CI) for OR and McNemar's χ 2 test. Multivariate analysis was carried out by conditional multiple logistic regression analysis. Attributable Risk Percent (ARP), Population Attributable Risk Percent (PARP) and their 95% CI were estimated for significant factors. On conditional multiple logistic regression five risk factors–hypertension (OR=1.9, 95% CI 1.5–2.5), serum total cholesterol (OR=2.3, 95% CI 1.4–4.9), use of anticoagulants and antiplatelet agents (OR=3.4, 95% CI 1.1–10.4), past history of transient ischaemic attack (OR=8.4, 95% CI 2.1–33.6) and alcohol intake (OR=2.1, 95% CI 1.3–3.6) were significant. Estimates of ARP and PARP for these factors confirmed their etiological and preventable role respectively. The current study recognised the significance of five risk factors, which are preventable. These risk factors may be considered for devising effective risk factor intervention strategy for haemorrhagic stroke. Public Health (2000) 114, 177–182

Identical Twins Who Are Discordant for Leber??s Hereditary Optic Neuropathy

Objective: Leber's hereditary optic neuropathy is a maternally inherited form of visual loss that is associated with several mitochondrial DNA mutations. These mitochondrial DNA mutations are not the sole determinants of visual loss, as epigenetic factors may play a pathogenetic role. To clarify the role of these factors, we studied two visually discordant twins and determined their zygosity and mitochondrial genotype. Design: Case series. Setting: Referral center. Patients: Identical twin brothers from a family with the 11778 mitochondrial DNA mutation. Main Outcome Measures: Visual acuity, results of testing for visual fields (measured with static and dynamic perimetry) and color vision, and results of funduscopic examination; alcohol and tobacco use, head trauma, coexistent medical illness, and occupational exposure; and results of mitochondrial DNA analysis and determination of zygosity. Results: The monozygous twin brothers have remained discordant for the development of optic neuropathy for 6 ½ years despite harboring the identical homoplasmic 4216, 13708, and 11778 mitochondrial DNA mutations. Conclusions: The patients are visually discordant despite being genetically identical at the nuclear and mitochondrial levels. Epigenetic factors are important determinants of visual loss in Leber's hereditary optic neuropathy in these brothers. Among those factors studied in these patients, a substantial difference was noted in regard to occupational exposure to toxic substances. Epigenetic factors that may influence the clinical expression of the mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy should be systematically studied. Risk-factor intervention strategies should be formulated and implemented.

Identical Twins Who Are Discordant for Leber's Hereditary Optic Neuropathy

Leber's hereditary optic neuropathy is a maternally inherited form of visual loss that is associated with several mitochondrial DNA mutations. These mitochondrial DNA mutations are not the sole determinants of visual loss, as epigenetic factors may play a pathogenetic role. To clarify the role of these factors, we studied two visually discordant twins and determined their zygosity and mitochondrial genotype. Case series. Referral center. Identical twin brothers from a family with the 11778 mitochondrial DNA mutation. Visual acuity, results of testing for visual fields (measured with static and dynamic perimetry) and color vision, and results of funduscopic examination; alcohol and tobacco use, head trauma, co-existent medical illness, and occupational exposure; and results of mitochondrial DNA analysis and determination of zygosity. The monozygous twin brothers have remained discordant for the development of optic neuropathy for 6 1/2 years despite harboring the identical homoplasmic 4216, 13708, and 11778 mitochondrial DNA mutations. The patients are visually discordant despite being genetically identical at the nuclear and mitochondrial levels. Epigenetic factors are important determinants of visual loss in Leber's hereditary optic neuropathy in these brothers. Among those factors studied in these patients, a substantial difference was noted in regard to occupational exposure to toxic substances. Epigenetic factors that may influence the clinical expression of the mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy should be systematically studied. Risk-factor intervention strategies should be formulated and implemented.

Risk factor intervention in Alzheimer's disease: Delay of onset by five years will halve morbidity

Alzheimer’s disease (AD) occurs mainly in late old age, but five independent studies (to be reviewed) suggest that 50% of the first degree relatives of AD probands are predisposed to develop AD by age 90. These data suggest that AD is a dominant genetic trait with expression that is complete but occurs mainly after age 75, when mortality from other causes also accelerates. Several non-genetic risk factors for AD have also been reported, e.g., head trauma, thyroid disease. If genetic susceptibility were both necessary and (eventually) sufficient for the development of AD (i.e.. penetrance is complete), then such risk factors would necessarily act by accelerating onset of AD. Even if genes played a lesser role in causing AD, such a mechanism might still hold. We therefore investigated the effects of a hypothetical risk factor intervention strategy that could delay the onset of AD by five years We began with two curves: (1) the age-specific probability density of AD onset (estimated from the above data); and (2) a similar curve with onset delayed by five years on average through risk factor intervention. The onset probabilities at each age were multiplied by the corresponding proportion surviving at that age (1980 Census) to yield “censored” curves of age-specific disease expression. The area under these curves reflects their total (censored) lifetime incidence of AD. The delayed onset curve shows 31% lower lifetime incidence. Later onset also shortens duration of illness, so prevalence (incidence Y duration) will be reduced overall by 50%. while disease severity among prevalent cases should also be lower (because of reduced illness duration). These results suggest that even modestly effective interventions in risk factors or their effects may produce dramatic reductions in morbidity from AD

Social class and risk factors for coronary heart disease in the Federal Republic of Germany. Results of the baseline survey of the German Cardiovascular Prevention Study (GCP).

The relationship between social class and seven important risk factors for coronary heart disease has been evaluated utilising data from the German Cardiovascular Prevention Study baseline survey. Of German residents aged 25 to 69 years, 16,430 were randomly selected from both the six intervention regions and the Federal Republic of Germany to undergo the screening procedures between 1984 and 1986. Among males the prevalence of cigarette smoking and lack of physical activity was associated with social class. For females, overweight and physical activity demonstrated a strong social gradient. No relationship existed between social class and hypercholesterolaemia. The prevalence of Type A behaviour was significantly higher for the upper social classes. The number of CHD risk factors per study subject increased with decreasing social class. Predicted cardiovascular mortality was clearly higher for the lower social class among males in general and for females younger than 60 years. These findings point to the need for risk factor intervention strategies focusing more on the lower social classes in order to achieve more adequate prevention of coronary heart disease.

Prospects for improving health through reducing risk factors

Intervention against both bodily risk factors such as hypertension, high serum cholesterol, cervical dysplasia, and trisomy 21; and behavioral risk factors such as cigarette smoking, too little exercise, and excessive alcohol consumption, offers improving prospects for reducing major current causes of death. The MRFIT program and other trials of intervention in North Karelia, Finland, and in northern California, are aimed at delineating how effective this strategy may be. Already it is clear that the risk factor intervention strategy may incorporate one or both of two tactics: the “medical model,” i.e., selecting individuals for intervention efforts on the basis of medical examinations; or the “community model,” i.e., directing efforts for risk factor reduction at a total community. This new approach to prevention represents a shift away from the clinical entities as the focus of medicine toward the identification and reduction of the factors that lead to clinical disease. The aim is not just to avoid clinical disease but to maintain health in the sense of physiologic function, anatomic regularity, chemical balance, genetic integrity, immunologic status, and healthful behavior.