论文信息 - Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes.

1996 - The New England journal of medicine

A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans.

BACKGROUND Cerebral cavernous malformation is a vascular disease of the brain causing headaches, seizures, and cerebral hemorrhage. Familial and sporadic cases are recognized, and a gene causing familial disease has been mapped to chromosome 7. Hispanic Americans have a higher prevalence of cavernous malformation than do other ethnic groups, raising the possibility that affected persons in this population have inherited the same mutation from a common ancestor. METHODS We compared the segregation of genetic markers and clinical cases of cavernous malformation in Hispanic-American kindreds with familial disease; we also compared the alleles for markers linked to cavernous malformation in patients with familial and sporadic cases. RESULTS All kindreds with familial disease showed linkage of cavernous malformation to a short segment of chromosome 7 (odds supporting linkage, 4X10(10).1). Forty-seven affected members of 14 kindreds shared identical alleles for up to 15 markers linked to the cavernous-malformation gene, demonstrating that they had inherited the same mutation from a common ancestor. Ten patients with sporadic cases also shared these same alleles, indicating that they too had inherited the same mutation. Thirty-three asymptomatic carriers of the disease gene were identified, demonstrating the variability and age dependence of the development of symptoms and explaining the appearance of apparently sporadic cases. CONCLUSIONS Virtually all cases of familial and sporadic cavernous malformation among Hispanic Americans of Mexican descent are due to the inheritance of the same mutation from a common ancestor.

2000 - Journal of periodontology

Smoking-attributable periodontitis in the United States: findings from NHANES III. National Health and Nutrition Examination Survey.

BACKGROUND The principal objectives of this study were to examine the relationship between cigarette smoking and periodontitis and to estimate the proportion of periodontitis in the United States adult population that is attributable to cigarette smoking. METHODS Data were derived from the Third National Health and Nutrition Examination Survey, a nationally representative multipurpose health survey conducted in 1988 to 1994. Participants were interviewed about tobacco use and examined by dentists trained to use standardized clinical criteria. Analysis was limited to dentate persons aged > or =18 years with complete clinical periodontal data and information on tobacco use and important covariates (n = 12,329). Data were weighted to provide U.S. national estimates, and analyses accounted for the complex sample design. We defined periodontitis as the presence of > or =1 site with clinical periodontal attachment level > or =4 mm apical to the cemento-enamel junction and probing depth > or =4 mm. Current cigarette smokers were those who had smoked > or =100 cigarettes over their lifetime and smoked at the time of the interview; former smokers had smoked > or =100 cigarettes but did not currently smoke; and never smokers had not smoked > or =100 cigarettes in their lifetime. RESULTS We found that 27.9% (95% confidence interval [CI]: +/-1.8%) of dentate adults were current smokers and 23.3% (95% CI: +/-1.2%) were former smokers. Overall, 9.2% (95% CI: +/-1.4%) of dentate adults met our case definition for periodontitis, which projects to about 15 million cases of periodontitis among U.S. adults. Modeling with multiple logistic regression revealed that current smokers were about 4 times as likely as persons who had never smoked to have periodontitis (prevalence odds ratio [ORp] = 3.97; 95% CI, 3.20-4.93), after adjusting for age, gender, race/ethnicity, education, and income:poverty ratio. Former smokers were more likely than persons who had never smoked to have periodontitis (ORp = 1.68; 95% CI, 1.31-2.17). Among current smokers, there was a dose-response relationship between cigarettes smoked per day and the odds of periodontitis (P <0.000001), ranging from ORp = 2.79 (95% CI, 1.90-4.10) for < or =9 cigarettes per day to ORp = 5.88 (95% CI, 4.03-8.58) for > or =31 cigarettes per day. Among former smokers, the odds of periodontitis declined with the number of years since quitting, from ORp = 3.22 (95% CI, 2.18-4.76) for 0 to 2 years to ORp = 1.15 (95% CI, 0.83-1.60) for > or =11 years. Applying standard epidemiologic formulas for the attributable fraction for the population, we calculated that 41.9% of periodontitis cases (6.4 million cases) in the U.S. adult population were attributable to current cigarette smoking and 10.9% (1.7 million cases) to former smoking. Among current smokers, 74.8% of their periodontitis was attributable to smoking. CONCLUSIONS Based on findings from this study and numerous other reports, we conclude that smoking is a major risk factor for periodontitis and may be responsible for more than half of periodontitis cases among adults in the United States. A large proportion of adult periodontitis may be preventable through prevention and cessation of cigarette smoking.

2013 - Nature

Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico

Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 × 10−13; odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 × 10−4; OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ∼50% frequency in Native American samples and ∼10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.

1997 - Neuroepidemiology

The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: the ARIC Study.

White matter lesions (WMLs) detected by cerebral magnetic resonance imaging (MRI) are putatively a consequence of cerebral hypoperfusion or ischemia. We investigated the prevalence, severity and correlates of WMLs in a population-based sample of 1,920 African-American and European-American men and women aged 55-72 years, during the second follow-up examination of the Atherosclerosis Risk in Communities Study. The spin density images from 1.5-tesla MRI scans were used to define WMLs using a 0-9 scale with 0 for normal and 9 for most severe WMLs. Age was positively associated with the prevalence (percent) and severity of WMLs. African-Americans had lower overall prevalence of WMLs, but a higher prevalence of relatively more severe WMLs, than European-Americans. After adjusting for age, sex, and ethnicity, WMLs were significantly associated with smoking, lower education, hypertension, systolic blood pressure, and pulse pressure, and weakly associated with diastolic blood pressure. The associations of smoking, alcohol intake, systolic and diastolic blood pressure, pulse, pressure, and hypertension were stronger in African-Americans than in European-Americans (p < 0.15 for interactions by ethnicity). This population-based MRI study documents significant relationships between several cardiovascular disease risk factors and WMLs. The findings suggest that such factors play a role in the pathogenesis of WMLs, an elements linked to hypoperfusion and/or fluid accumulation, which presumably lead to WMLs. African-Americans exhibited both a higher proportion of normal white matter and a higher proportion of relatively more severe WMLs than European-Americans.

2017 - JAMA cardiology

Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality: A Systematic Review and Network Meta-analysis

Importance Clinical trials have documented that lowering blood pressure reduces cardiovascular disease and premature deaths. However, the optimal target for reduction of systolic blood pressure (SBP) is uncertain. Objective To assess the association of mean achieved SBP levels with the risk of cardiovascular disease and all-cause mortality in adults with hypertension treated with antihypertensive therapy. Data Sources MEDLINE and EMBASE were searched from inception to December 15, 2015, supplemented by manual searches of the bibliographies of retrieved articles. Study Selection Studies included were clinical trials with random allocation to an antihypertensive medication, control, or treatment target. Studies had to have reported a difference in mean achieved SBP of 5 mm Hg or more between comparison groups. Data Extraction and Synthesis Data were extracted from each study independently and in duplicate by at least 2 investigators according to a standardized protocol. Network meta-analysis was used to obtain pooled randomized results comparing the association of each 5–mm Hg SBP category with clinical outcomes after adjusting for baseline risk. Main Outcomes and Measures Cardiovascular disease and all-cause mortality. Results Forty-two trials, including 144 220 patients, met the eligibility criteria. In general, there were linear associations between mean achieved SBP and risk of cardiovascular disease and mortality, with the lowest risk at 120 to 124 mm Hg. Randomized groups with a mean achieved SBP of 120 to 124 mm Hg had a hazard ratio (HR) for major cardiovascular disease of 0.71 (95% CI, 0.60-0.83) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.58 (95% CI, 0.48-0.72) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.46 (95% CI, 0.34-0.63) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.36 (95% CI, 0.26-0.51) compared with those with a mean achieved SBP of 160 mm Hg or more. Likewise, randomized groups with a mean achieved SBP of 120 to 124 mm Hg had an HR for all-cause mortality of 0.73 (95% CI, 0.58-0.93) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.59 (95% CI, 0.45-0.77) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.51 (95% CI, 0.36-0.71) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.47 (95% CI, 0.32-0.67) compared with those with a mean achieved SBP of 160 mm Hg or more. Conclusions and Relevance This study suggests that reducing SBP to levels below currently recommended targets significantly reduces the risk of cardiovascular disease and all-cause mortality. These findings support more intensive control of SBP among adults with hypertension.

2009 - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology.

BACKGROUND Nontuberculous mycobacteria (NTM) are important human pathogens, yet little is known about disease prevalence in the United States. Reports suggest prevalence has increased, particularly in women, but population-based data to substantiate this are lacking. We sought to estimate NTM disease prevalence in Oregon, and describe disease by site, species, and patient demographic characteristics. METHODS We contacted laboratories that performed mycobacterial cultures on Oregon residents in 2005-2006. For each isolate, we obtained source, collection date, species, and patient demographics. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease. RESULTS We identified 933 patients with > or =1 NTM isolate. Of these, 527 (56%) met the case definition (annualized prevalence, 7.2 cases per 100,000 persons). Pulmonary cases predominated (5.6 cases per 100,000 persons), followed by skin/soft-tissue cases (0.9 cases per 100,000 persons). Mycobacterium avium complex was the most common species identified in pulmonary cases (4.7 cases per 100,000 persons). Pulmonary disease prevalence was significantly higher in women (6.4 cases per 100,000 persons) than men (4.7 cases per 100,000 persons) and was highest in persons aged >50 years (15.5 cases per 100,000 persons). CONCLUSIONS NTM are frequently isolated from Oregon residents; more than one-half of all isolates likely represent true disease. Pulmonary NTM is most common among elderly women, and M. avium causes most disease. Future efforts to monitor disease trends should be undertaken, and efforts made to validate the use of the ATS/IDSA microbiologic criteria alone to predict pulmonary NTM disease.

2006 - Archives of internal medicine

Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study.

BACKGROUND Small, short-term, intervention studies indicate that cocoa-containing foods improve endothelial function and reduce blood pressure. We studied whether habitual cocoa intake was cross-sectionally related to blood pressure and prospectively related with cardiovascular mortality. METHODS Data used were of 470 elderly men participating in the Zutphen Elderly Study and free of chronic diseases at baseline. Blood pressure was measured at baseline and 5 years later, and causes of death were ascertained during 15 years of follow-up. Habitual food consumption was assessed by the cross-check dietary history method in 1985, 1990, and 1995. Cocoa intake was estimated from the consumption of cocoa-containing foods. RESULTS One third of the men did not use cocoa at baseline. The median cocoa intake among users was 2.11 g/d. After adjustment, the mean systolic blood pressure in the highest tertile of cocoa intake was 3.7 mm Hg lower (95% confidence interval [CI], -7.1 to -0.3 mm Hg; P = .03 for trend) and the mean diastolic blood pressure was 2.1 mm Hg lower (95% CI, -4.0 to -0.2 mm Hg; P = .03 for trend) compared with the lowest tertile. During follow-up, 314 men died, 152 of cardiovascular diseases. Compared with the lowest tertile of cocoa intake, the adjusted relative risk for men in the highest tertile was 0.50 (95% CI, 0.32-0.78; P = .004 for trend) for cardiovascular mortality and 0.53 (95% CI, 0.39-0.72; P < .001) for all-cause mortality. CONCLUSION In a cohort of elderly men, cocoa intake is inversely associated with blood pressure and 15-year cardiovascular and all-cause mortality.

2011 - Digestion

Systematic Review of the Epidemiology of Complicated Peptic Ulcer Disease: Incidence, Recurrence, Risk Factors and Mortality

Background/Aims: The incidence of uncomplicated peptic ulcer has decreased in recent years. It is unclear what the impact of this has been on the epidemiology of peptic ulcer complications. This systematic review aimed to determine the incidence, recurrence and mortality of complicated peptic ulcer and the risk factors associated with these events. Methods: Systematic PubMed searches. Results: Overall, 93 studies were identified. Annual incidence estimates of peptic ulcer hemorrhage and perforation were 19.4–57.0 and 3.8–14 per 100,000 individuals, respectively. The average 7-day recurrence of hemorrhage was 13.9% (95% CI: 8.4–19.4), and the average long-term recurrence of perforation was 12.2% (95% CI: 2.5–21.9). Risk factors for peptic ulcer complications and their recurrence included nonsteroidal anti-inflammatory drug and/or acetylsalicylic acid use, Helicobacter pylori infection and ulcer size ≧1 cm. Proton pump inhibitor use reduced the risk of peptic ulcer hemorrhage. Average 30-day mortality was 8.6% (95% CI: 5.8–11.4) after hemorrhage and 23.5% (95% CI: 15.5–31.0) after perforation. Older age, comorbidity, shock and delayed treatment were associated with increased mortality. Conclusions: Complicated peptic ulcer remains a substantial healthcare problem which places patients at a high risk of recurrent complications and death.

1998 - Hypertension

Baroreflex control of sympathetic nerve activity in essential and secondary hypertension.

Studies performed in experimental animals and in humans have documented that high blood pressure markedly impairs baroreceptor control of heart rate. Whether a similar impairment also characterizes baroreceptor control of sympathetic activity modulating peripheral vasomotor tone is still unknown. In 28 untreated essential hypertensive subjects [14 of moderate and 14 of more severe degree, age 51.6+/-2.4 and 52.6+/-2.1 years (mean+/-SEM)] and in 13 untreated secondary hypertensives (renovascular or pheochromocytoma, age 50.1+/-4.6 years), we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram), and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 15 age-matched normotensive control subjects. Muscle sympathetic nerve activity (bursts per 100 heart beats) showed a progressive and significant (P<.01) increase from normotension (40.3+/-3.3) to moderate (55.6+/-4.1) and more severe essential hypertension (68.2+/-4.1), paralleling the progressive increase in blood pressure values. In contrast, muscle sympathetic nerve activity was not increased in secondary hypertensives (40.5+/-6.7) despite blood pressure values similar to or even greater than those of severe essential hypertensives. In both essential and secondary hypertensives, baroreceptor-heart rate control was displaced toward elevated blood pressure values and markedly impaired compared with normotensive subjects (average reduction, 38.5%). In contrast, the sympathoinhibitory and sympathoexcitatory responses to baroreceptor stimulation and deactivation were displaced toward elevated blood pressure values but similar in all groups. Thus, sympathetic activation characterizes essential but not secondary hypertension. Regardless of its nature, however, hypertension is not accompanied by an impairment of baroreceptor modulation of sympathetic activity.

2000 - Hypertension

Arterial hypertension, microalbuminuria, and risk of ischemic heart disease.

Albumin excretion in urine is positively correlated with the presence of ischemic heart disease and atherosclerotic risk factors. We studied prospectively whether a slight increase of urinary albumin excretion, ie, microalbuminuria, adds to the increased risk of ischemic heart disease among hypertensive subjects. In 1983 and 1984, blood pressure, urinary albumin/creatinine concentration ratio, plasma total and HDL cholesterol levels, body mass index, and smoking status were obtained in a population-based sample of 2085 subjects, aged 30 to 60 years, who were free from ischemic heart disease, diabetes mellitus, and renal or urinary tract disease. Untreated arterial hypertension or borderline hypertension was present in 204 subjects, who were followed until 1993 by the National Hospital and Death Certificate Registers with respect to development of ischemic heart disease. During 1978 person-years, 18 (9%) of the hypertensive subjects developed ischemic heart disease. Microalbuminuria, defined as a urinary albumin/creatinine ratio above the upper decile (1.07 mg/mmol), was the strongest predictor of ischemic heart disease, with an unadjusted relative risk of 4.2 (95% CI 1.5 to 11.9, P=0.006) and a relative risk of 3.5 (95% CI 1.0 to 12.1, P=0.05) when adjusted for all other atherosclerotic risk factors, including age and gender. In conclusion, microalbuminuria confers a 4-fold increased risk of ischemic heart disease among hypertensive or borderline hypertensive subjects. Urinary albumin excretion should be measured regularly in a hypertension clinic, and a rigorous control of blood pressure and of other atherosclerotic risk factors is recommended in hypertensive patients with microalbuminuria.

2001 - American journal of respiratory and critical care medicine

Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome.

Arterial blood pressure rises at apnea termination, and there is increasing evidence that the sleep apnea-hypopnea syndrome (SAHS) is associated with daytime hypertension but no randomized controlled trial evidence of whether SAHS treatment reduces blood pressure exists. We, therefore, conducted a randomized placebo-controlled cross-over study of the effects of 4 wk of continuous positive airway pressure (CPAP) or oral placebo on 24-h blood pressure in 68 patients (55 males, 13 females; median apnea-hypopnea index [AHI], 35) not receiving hypotensive medication. Ambulatory blood pressure was recorded for the last 48 h of each treatment. Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also recorded. All patients were normotensive. There was a small decrease in 24-h diastolic blood pressure (placebo, 79.2 [SE 0.9] mm Hg; CPAP, 77.8 [SE 1.0] mm Hg; p = 0.04) with the greatest fall occurring between 2:00 A.M. and 9:59 A.M. The observed decrease in 24-h diastolic blood pressure was greater in two a priori groups, CPAP use > or = 3.5 h per night (81.5 [SE 1.2] mm Hg; 79.6 [SE 1.2] mm Hg; p = 0.03) and those with more than twenty 4% desaturations per hour (82.4 [SE 2.1] mm Hg; 77.4 [SE 2.1] mm Hg; p = 0.002). Systolic pressure also fell in the latter group (133.1 [SE 2.8] mm Hg; 129.1 [SE 2.1] mm Hg; p = 0.009). Desaturation frequency was the best predictor of diastolic blood pressure fall with CPAP (r = 0.38; p = 0.002). Both ESS and FOSQ domains improved. Thus, CPAP can reduce blood pressure in patients with SAHS, particularly in those with nocturnal oxygen desaturation, but the decrease is small.

2015 - Lancet (London, England)

Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial

Summary Background Optimal drug treatment for patients with resistant hypertension is undefined. We aimed to test the hypotheses that resistant hypertension is most often caused by excessive sodium retention, and that spironolactone would therefore be superior to non-diuretic add-on drugs at lowering blood pressure. Methods In this double-blind, placebo-controlled, crossover trial, we enrolled patients aged 18–79 years with seated clinic systolic blood pressure 140 mm Hg or greater (or ≥135 mm Hg for patients with diabetes) and home systolic blood pressure (18 readings over 4 days) 130 mm Hg or greater, despite treatment for at least 3 months with maximally tolerated doses of three drugs, from 12 secondary and two primary care sites in the UK. Patients rotated, in a preassigned, randomised order, through 12 weeks of once daily treatment with each of spironolactone (25–50 mg), bisoprolol (5–10 mg), doxazosin modified release (4–8 mg), and placebo, in addition to their baseline blood pressure drugs. Random assignment was done via a central computer system. Investigators and patients were masked to the identity of drugs, and to their sequence allocation. The dose was doubled after 6 weeks of each cycle. The hierarchical primary endpoints were the difference in averaged home systolic blood pressure between spironolactone and placebo, followed (if significant) by the difference in home systolic blood pressure between spironolactone and the average of the other two active drugs, followed by the difference in home systolic blood pressure between spironolactone and each of the other two drugs. Analysis was by intention to treat. The trial is registered with EudraCT number 2008-007149-30, and ClinicalTrials.gov number, NCT02369081. Findings Between May 15, 2009, and July 8, 2014, we screened 436 patients, of whom 335 were randomly assigned. After 21 were excluded, 285 patients received spironolactone, 282 doxazosin, 285 bisoprolol, and 274 placebo; 230 patients completed all treatment cycles. The average reduction in home systolic blood pressure by spironolactone was superior to placebo (–8·70 mm Hg [95% CI −9·72 to −7·69]; p<0·0001), superior to the mean of the other two active treatments (doxazosin and bisoprolol; −4·26 [–5·13 to −3·38]; p<0·0001), and superior when compared with the individual treatments; versus doxazosin (–4·03 [–5·04 to −3·02]; p<0·0001) and versus bisoprolol (–4·48 [–5·50 to −3·46]; p<0·0001). Spironolactone was the most effective blood pressure-lowering treatment, throughout the distribution of baseline plasma renin; but its margin of superiority and likelihood of being the best drug for the individual patient were many-fold greater in the lower than higher ends of the distribution. All treatments were well tolerated. In six of the 285 patients who received spironolactone, serum potassium exceeded 6·0 mmol/L on one occasion. Interpretation Spironolactone was the most effective add-on drug for the treatment of resistant hypertension. The superiority of spironolactone supports a primary role of sodium retention in this condition. Funding The British Heart Foundation and National Institute for Health Research.

1985 - Journal of applied physiology

Arterial blood pressure response to heavy resistance exercise.

The purpose of this study was to record the blood pressure response to heavy weight-lifting exercise in five experienced body builders. Blood pressure was directly recorded by means of a capacitance transducer connected to a catheter in the brachial artery. Intrathoracic pressure with the Valsalva maneuver was recorded as mouth pressure by having the subject maintain an open glottis while expiring against a column of Hg during the lifts. Exercises included single-arm curls, overhead presses, and both double- and single-leg presses performed to failure at 80, 90, 95, and 100% of maximum. Systolic and diastolic blood pressures rose rapidly to extremely high values during the concentric contraction phase for each lift and declined with the eccentric contraction. The greatest peak pressures occurred during the double-leg press where the mean value for the group was 320/250 mmHg, with pressures in one subject exceeding 480/350 mmHg. Peak pressures with the single-arm curl exercise reached a mean group value of 255/190 mmHg when repetitions were continued to failure. Mouth pressures of 30-50 Torr during a single maximum lift, or as subjects approached failure with a submaximal weight, indicate that a portion of the observed increase in blood pressure was caused by a Valsalva maneuver. It was concluded that when healthy young subjects perform weight-lifting exercises the mechanical compression of blood vessels combines with a potent pressor response and a Valsalva response to produce extreme elevations in blood pressure. Pressures are extreme even when exercise is performed with a relatively small muscle mass.

1998 - Annals of periodontology

Periodontal disease and diabetes mellitus: a two-way relationship.

Severe periodontal disease often coexists with severe diabetes mellitus. Diabetes is a risk factor for severe periodontal disease. A model is presented whereby severe periodontal disease increases the severity of diabetes mellitus and complicates metabolic control. We propose that an infection-mediated upregulation cycle of cytokine synthesis and secretion by chronic stimulus from lipopolysaccharide (LPS) and products of periodontopathic organisms may amplify the magnitude of the advanced glycation end product (AGE)-mediated cytokine response operative in diabetes mellitus. In this model, the combination of these 2 pathways, infection and AGE-mediated cytokine upregulation, helps explain the increase in tissue destruction seen in diabetic periodontitis, and how periodontal infection may complicate the severity of diabetes and the degree of metabolic control, resulting in a 2-way relationship between diabetes mellitus and periodontal disease/infection. This proposed dual pathway of tissue destruction suggests that control of chronic periodontal infection is essential for achieving long-term control of diabetes mellitus. Evidence is presented to support the hypothesis that elimination of periodontal infection by using systemic antibiotics improves metabolic control of diabetes, defined by reduction in glycated hemoglobin or reduction in insulin requirements.

1993 - Archives of internal medicine

Blood pressure, systolic and diastolic, and cardiovascular risks. US population data.

The National High Blood Pressure Education Program (NHBPEP) was launched 20 years ago based on data from population studies and clinical trials that showed high blood pressure (HBP) was a major unsolved--but soluble--mass public health problem. The present review summarizes recent data from US prospective population studies on blood pressure--systolic (SBP), diastolic (DBP)--and cardiovascular risk. The outcome variables include blood pressure-related risks, primarily incidence and mortality from coronary heart disease, stroke, other and all cardiovascular diseases (CVD); also cardiac abnormalities (roentgenographic, electrocardiographic, echocardiographic); also, all-cause mortality and life expectancy. Data accrued during the past 20 years confirm that SBP and DBP have continuous, graded, strong, independent, etiologically significant relationships to the outcome variables. These relationships are documented for young, middle-aged, and older men and for middle-aged and older women of varying socioeconomic backgrounds and ethnicity. Among persons aged 35 years or more, most have SBP/DBP above optimal (< 120/< 80 mm Hg); hence, they are at increased CVD risk, ie, the blood pressure problem involves most of the population, not only the substantial minority with clinical HBP. For middle-aged and older persons, SBP relates even more strongly to risk than DBP; at every DBP level, higher SBP results in greater CVD risk and curtailment of life expectancy. A great potential exists for improved health and increased longevity through control of the blood pressure problem. Its realization requires a strategy combining population wide and high-risk approaches, the former to prevent rise of blood pressure with age and to achieve primary prevention of HBP by nutritional-hygienic means; the latter to enhance detection, treatment, and control of HBP. The newly expanded goals of the NHBPEP, aimed at implementing this broader strategy for the solution of the blood pressure problem, merit active support from physicians and all health professionals.

1996 - Journal of the National Cancer Institute

Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial.

BACKGROUND For many years, high dose radiation therapy was the standard treatment for patients with locally or regionally advanced non-small-cell lung cancer (NSCLC), despite a 5-year survival rate of only 3%-10% following such therapy. From May 1984 through May 1987, the Cancer and Leukemia Group B (CALGB) conducted a randomized trial that showed that induction chemotherapy before radiation therapy improved survival during the first 3 years of follow-up. PURPOSE This report provides data for 7 years of follow-up of patients enrolled in the CALGB trial. METHODS The patient population consisted of individuals who had clinical or surgical stage III, histologically documented NSCLC; a CALGB performance status of 0-1; less than 5% loss of body weight in the 3 months preceding diagnosis; and radiographically visible disease. Patients were randomly assigned to receive either 1) cisplatin (100 mg/m2 body surface area intravenously on days 1 and 29) and vinblastine (5 mg/m2 body surface area intravenously weekly on days 1, 8, 15, 22, and 29) followed by radiation therapy with 6000 cGy given in 30 fractions beginning on day 50 (CT-RT group) or 2) radiation therapy with 6000 cGy alone beginning on day 1 (RT group) for a maximum duration of 6-7 weeks. Patients were evaluated for tumor regression if they had measurable or evaluable disease and were monitored for toxic effects, disease progression, and date of death. RESULTS There were 78 eligible patients randomly assigned to the CT-RT group and 77 randomly assigned to the RT group. Both groups were similar in terms of sex, age, histologic cell type, performance status, substage of disease, and whether staging had been clinical or surgical. All patients had measurable or evaluable disease at the time of random assignment to treatment groups. Both groups received a similar quantity and quality of radiation therapy. As previously reported, the rate of tumor response, as determined radiographically, was 56% for the CT-RT group and 43% for the RT group (P = .092). After more than 7 years of follow-up, the median survival remains greater for the CT-RT group (13.7 months) than for the RT group (9.6 months) (P = .012) as ascertained by the logrank test (two-sided). The percentages of patients surviving after years 1 through 7 were 54, 26, 24, 19, 17, 13, and 13 for the CT-RT group and 40, 13, 10, 7, 6, 6, and 6 for the RT group. CONCLUSIONS Long-term follow-up confirms that patients with stage III NSCLC who receive 5 weeks of chemotherapy with cisplatin and vinblastine before radiation therapy have a 4.1-month increase in median survival. The use of sequential chemotherapy-radiotherapy increases the projected proportion of 5-year survivors by a factor of 2.8 compared with that of radiotherapy alone. However, inasmuch as 80%-85% of such patients still die within 5 years and because treatment failure occurs both in the irradiated field and at distant sites in patients receiving either sequential chemotherapy-radiotherapy or radiotherapy alone, the need for further improvements in both the local and systemic treatment of this disease persists.

2013 - JAMA

Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.

IMPORTANCE Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. OBJECTIVE To identify genetic loci associated with late-onset Alzheimer disease in African Americans. DESIGN, SETTING, AND PARTICIPANTS The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. MAIN OUTCOMES AND MEASURES Presence of Alzheimer disease according to standardized criteria. RESULTS Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8 < D' < 0.9). The effect size for the SNP in ABCA7 was comparable with that of the APOE ϵ4-determining SNP rs429358 (allele = C; frequency, 0.30 cases and 0.18 controls; OR, 2.31 [95% CI, 2.19-2.42]; P = 5.5 × 10(-47)). Several loci previously associated with Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005 < empirical P < .001). CONCLUSIONS AND RELEVANCE In this meta-analysis of data from African American participants, Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional validation of this finding is needed before this information is used in clinical settings.

2002 - Diabetes care

Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam.

OBJECTIVE To determine whether components of the metabolic syndrome precede the 5-year incidence of cardiovascular disease and diabetes. RESEARCH DESIGN AND METHODS A population of individuals aged 43-84 years was evaluated from 1988 to 1990 and again 5 years later. Medical history, blood pressure, and laboratory measures were obtained at both examinations following the same protocols. Subjects without diabetes were classified according to level of glycemia, high blood pressure, high-risk lipid levels, high uric acid levels, and proteinuria at baseline. History of incident myocardial infarction, angina, stroke, and diabetes was obtained at follow-up. RESULTS Of the 4,423 subjects without diabetes, 6.9% had elevated levels of glycemia, 18.4% had high blood pressure, 82.7% had high-risk lipid levels (either high serum total cholesterol or low HDL cholesterol or high ratio of these two levels), 27% had elevated uric acid levels, 33.2% had high BMI, and 3.3% had proteinuria (> or =30 mg/dl). The risk of incident cardiovascular disease 5 years later increased with the number of the components present; 2.5% of those with one component developed cardiovascular disease, whereas 14.9% of those with four or more components developed cardiovascular disease. Of those with one component, diabetes developed in 1.1% 5 years later, whereas diabetes developed in 17.9% of those with four or more components. CONCLUSIONS Components of the metabolic syndrome are common and are associated with incident cardiovascular disease and diabetes after 5 years. Interventions to alter BMI, lipid levels, and blood pressure may decrease incident diabetes and cardiovascular disease.

2009 - Hypertension

Dissociation of Aortic Pulse Wave Velocity With Risk Factors for Cardiovascular Disease Other Than Hypertension: A Systematic Review

Carotid-femoral pulse wave velocity (cfPWV), a measure of large artery stiffness, is an important predictor of cardiovascular events. This has been attributed to it being an integrative measure of the impact of cardiovascular risk factors on the arterial wall. Pulse wave velocity is strongly associated with age and blood pressure. However, findings with regard to its relation with other risk factors have been inconsistent. We performed a systematic review of cross-sectional published literature reporting independent associations of cfPWV in multivariable regression models. Articles were selected from a PubMed search using a prespecified search strategy. Studies were included if they did the following: (1) measured cfPWV; (2) reported on associations with cfPWV from regression models; and (3) considered age and blood pressure in the model. From 637 retrieved articles, 65 met our inclusion criteria, and 12 studies were included from reference searches. Age and blood pressure were consistently independently associated with cfPWV (91% and 90% of studies, respectively). Diabetes mellitus was associated with cfPWV in 52% studies, but the strength of the association was low. The majority of studies found no independent association between cfPWV and sex, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, or body mass index. The contribution of risk factors other than age and blood pressure to cfPWV is, thus, small or insignificant. The prognostic value of cfPWV may relate to a process of arterial ageing unrelated to classic risk factors other than hypertension.

1991 - JAMA

Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study.

We report here the 14-year sex-specific effect of non-insulin-dependent diabetes mellitus on the risk of fatal ischemic heart disease in a geographically defined population of men and women aged 40 through 79 years. There were 207 men and 127 women who had diabetes at baseline based on medical history or fasting hyperglycemia. They were compared with 2137 adults who had fasting euglycemia and a negative personal and family history of diabetes. The relative hazard of ischemic heart disease death in diabetics vs nondiabetics was 1.8 in men and 3.3 in women, after adjusting for age, and 1.9 and 3.3, respectively, after adjusting for age, systolic blood pressure, cholesterol, body mass index, and cigarette smoking using the Cox regression model. The sex difference in the independent contribution of diabetes to fatal heart disease was largely explained by the persistently more favorable survival rate of women (than men) without diabetes.

Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes.

Oxidative stress, glucose metabolism, and the prevention of type 2 diabetes: pathophysiological insights.

The burgeoning public health impact of diabetes: the role of the ophthalmologist.

Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.

Cardiovascular Outcomes in Framingham Participants With Diabetes: The Importance of Blood Pressure

Glucokinase activators in diabetes management

Cardiovascular and renal benefits of dapagliflozin in patients with short and long‐standing type 2 diabetes: Analysis from the DECLARE‐TIMI 58 trial

Meeting American Diabetes Association diabetes management targets: trends in Mauritius

Rosiglitazone plus metformin is effective and well tolerated in clinical practice: results from large observational studies in people with type 2 diabetes

Efficacy and Safety of Ertugliflozin in Patients with Overweight and Obesity with Type 2 Diabetes Mellitus

ASH Position Paper: Treatment of Hypertension in Patients With Diabetes—An Update

Linhas de Fuga no Processo Artístico com a Tecnologia Digital * (Digital Technology and Art Crossings Generating Fugue Lines on Creation Processes)

Closing Statement: What Have We Said About Computation?

Pulmonary Delivery as a Route for Insulin

Bridging the knowledge—action gap in diabetes: information technologies, physician incentives and consumer incentives converge

Patient-Centered Medical Home and Diabetes

Current challenges in diabetes management.

Review of the Effect of Dairy Products on Non-Lipid Risk Factors for Cardiovascular Disease

Metabolic Surgery for Type 2 Diabetes: Changing the Landscape of Diabetes Care

Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease

Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus