30 Year patterns of mortality in Tobago, West Indies, 1976-2005: impact of glucose intolerance and alcohol intake

Objectives

To determine the main predictors of all-cause and cardiovascular (CV) mortality in a rural West Indian population in Plymouth, Tobago over 30 years.

Methods

Questionnaire survey for CV risk factors and alcohol consumption patterns administered at baseline in 1976 with 92.5% response rate. 831/832 patients were followed up until 2005 or death.

Results

Hypertension (>140/90 mm Hg) was prevalent in 48% of men and 44% of women, and 21% of men and 17% of women had diabetes. Evidence showed most predictors for all cause and cardiovascular mortality having the main effects at ages <60 years, (p-value for interaction<0.01) but no risk factors having sex-specific effects on mortality. The main predictors of all-cause mortality at age <60 years in the fully adjusted model were high sessional alcohol intake (hazard ratio (HR) 2.04, 95% CI 1.10-3.80), severe hypertension >160/95 mm Hg (HR 1.68, 95% CI 1.09-2.60), diabetes (HR 3.28, 95% CI 1.89-5.69), and BMI (HR 1.04, 95% CI 1.00-1.07). The main predictors of cardiovascular mortality were similar in the fully adjusted model: high sessional alcohol intake (HR 2.47 95% CI 1.10-5.57), severe hypertension (HR 2.78 95% CI 1.56-4.95), diabetes (HR 3.68 95% CI 1.77-7.67) and additionally LVH, (HR 5.54 95% CI 1.38-22.26), however BMI did not show independent effects. For men, high sessional alcohol intake explains 27% of all cause mortality, and 40% of cardiovascular mortality at age <60 yrs. In adults aged <60 years, the attributable risk fraction for IGT/Diabetes and all cause mortality and cardiovascular mortality is 28% in women vs. 11% in men, and 22% in women vs. 6% in men respectively.

Conclusions

In this Afro-Caribbean population we found that a major proportion of deaths are attributable to high sessional alcohol intake (in males), diabetes, and hypertension and these risk factors primarily operate in those below 60 years.     

Aromatase gene polymorphisms are associated with survival among patients with cardiovascular disease in a sex-specific manner

Introduction

CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes.

Methods

Caucasian individuals from two independent populations were assessed: 1) a prospective cohort of patients with acute coronary syndromes with 3-year mortality follow-up (n = 568) and 2) a nested case-control study from a randomized, controlled trial of hypertension patients with stable coronary disease in which the primary outcome was death, nonfatal myocardial infarction (MI) or nonfatal stroke (n = 619). Six CYP19A1 SNPs were genotyped (-81371 C>T, -45965 G>C, M201T, R264C, 80 A>G, and +32226 G>A). The sex*genotype interaction term was assessed for the primary outcome and compared by genotype in men and women when a significant interaction term was identified.

Results

We identified a significant interaction between -81371 C>T and sex (p = 0.025) in the ACS population. The variant allele was associated with a 78% increase in mortality in men (HR 1.78, 95% confidence interval [CI] 1.08-2.94) and a nonsignificant 42% decrease in mortality among women (HR 0.58, 95% CI 0.22-1.54). We identified a similar association in the hypertensive CAD group, the -81371 C>T*sex interaction term was p<0.0001, with an associated 65% increase in death, MI, or stroke (HR 1.65, 95% CI 1.00-2.73) in men and a 69% decrease (HR 0.31, 95% CI 0.16-0.6) in women.

Conclusions

Using two independent populations, this study is the first to document a significant interaction between CYP19A1 genotype and sex on cardiovascular outcomes. These findings could illuminate potential mechanisms of sex differences in cardiovascular disease outcomes.     

Hypertension and obesity as cardiovascular risk factors among HIV seropositive patients in Western Kenya

Background

There is increased risk of cardiovascular disease among HIV seropositive individuals. The prevalence of HIV is highest in sub-Saharan Africa; however, HIV-related cardiovascular risk research is largely derived from developed country settings. Herein, we describe the prevalence of hypertension and obesity in a large HIV treatment program in Kenya.

Methods

We performed a retrospective analysis of the electronic medical records of a large HIV treatment program in Western Kenya between 2006 and 2009. We calculated the prevalence of hypertension and obesity among HIV+ adults as well as utilized multiple logistic regression analyses to examine the relationship between clinical characteristics, HIV-related characteristics, and hypertension.

Results

Our final sample size was 12,194. The median systolic/diastolic blood pressures were similar for both sexes (male: 110/70 mmHg, female: 110/70 mmHg). The prevalence of hypertension among men and women were 11.2% and 7.4%, respectively. Eleven percent of men and 22.6% of women were overweight/obese (body mass index ≥25 kg/m²). Ordinal logistic regression analyses showed that overweight/obesity was more strongly associated with hypertension among HIV+ men (OR 2.41, 95% CI 1.88–3.09) than a higher successive age category (OR 1.62, 95% CI 1.40–1.87 comparing 16–35, 36–45 and >45 years categories). Among women, higher age category and overweight/obesity were most strongly associated with hypertension (age category: OR 2.21, 95% CI 1.95–2.50, overweight/obesity: OR 1.80, 95% CI 1.50–2.16). Length of time on protease inhibitors was not found to be related to hypertension for men (OR 1.62, 95% CI 0.42–6.20) or women (OR 1.17, 95% CI 0.37–2.65) after adjustment for CD4 count, age and BMI.

Conclusion

In Western Kenya, there is a high prevalence of hypertension and overweight/obesity among HIV+ patients with differences observed between men and women. The care of HIV+ patients in sub-Saharan Africa should also include both identification and management of associated cardiovascular risk factors.     

Raw and processed fruit and vegetable consumption and 10-year coronary heart disease incidence in a population-based cohort study in the Netherlands

Background

Prospective cohort studies have shown that high fruit and vegetable consumption is inversely associated with coronary heart disease (CHD). Whether food processing affects this association is unknown. Therefore, we quantified the association of fruit and vegetable consumption with 10-year CHD incidence in a population-based study in the Netherlands and the effect of processing on these associations.

Methods

Prospective population-based cohort study, including 20,069 men and women aged 20 to 65 years, enrolled between 1993 and 1997 and free of cardiovascular disease at baseline. Diet was assessed using a validated 178-item food frequency questionnaire. Hazard ratios (HR) were calculated for CHD incidence using multivariable Cox proportional hazards models.

Results

During a mean follow-up time of 10.5y, 245 incident cases of CHD were documented, which comprised 211 non-fatal acute myocardial infarctions and 34 fatal CHD events. The risk of CHD incidence was 34% lower for participants with a high intake of total fruit and vegetables (>475 g/d; HR: 0.66; 95% CI: 0.45–0.99) compared to participants with a low total fruit and vegetable consumption (≤241 g/d). Intake of raw fruit and vegetables (>262 g/d vs ≤92 g/d; HR: 0.70; 95% CI: 0.47–1.04) as well as processed fruit and vegetables (>234 g/d vs ≤113 g/d; HR: 0.79; 95% CI: 0.54–1.16) were inversely related with CHD incidence.

Conclusion

Higher consumption of fruit and vegetables, whether consumed raw or processed, may protect against CHD incidence.     

Gender-specific associations of marine n-3 fatty acids and fish consumption with 10-year incidence of stroke

Background

There is some evidence that the association of fish and marine fatty acids with stroke risk differs between men and women. We investigated the gender-specific associations of habitual intake of the marine fatty acids eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) and fish on incident stroke in a population-based study in the Netherlands.

Methods

We prospectively followed 20,069 men and women, aged 20–65 years, without cardiovascular diseases at baseline. Habitual diet was assessed with a validated 178-item food frequency questionnaire. Incidence of stroke was assessed through linkage with mortality and morbidity registers. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95%CI).

Results

During 8–13 years of follow-up, 221 strokes occurred. In women, an inverse dose-response relation (P-trend = 0.02) was observed between EPA-DHA intake and incident stroke, with an HR of 0.49 (95% CI: 0.27–0.91) in the top quartile of EPA-DHA (median 225 mg/d) as compared to the bottom quartile (median 36 mg/d). In men, the HR (95%CI) for the top quartile of EPA-DHA intake was 0.87 (0.51–1.48) (P-trend = 0.36). Similar results were observed for fish consumption and stroke incidence.

Conclusion

A higher EPA-DHA and fish intake is related to a lower stroke risk in women, while for men an inverse association could not be demonstrated.     

Body adiposity in later life and the incidence of dementia: the health in men study

Objective

To determine if adiposity in later life increases dementia hazard.

Methods

Cohort study of 12,047 men aged 65–84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease.

Results

Compared with men with BMI<25, participants with BMI between 25–30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70–0.95). The HR of dementia for men with BMI≥30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67–1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR≥0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI = 0.69–0.98). We found a “J” shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR.

Conclusions

Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR≥0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9.     

Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction, and cause-specific mortality: cohort study

Objective

Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.

Design

The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).

Results

Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.

Conclusion

In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.     

Sex differences in risk factors for cardiovascular disease: the PERU MIGRANT study

Introduction

Although men and women have similar risk factors for cardiovascular disease, many social behaviors in developing countries differ by sex. Rural-to-urban migrants have different cardiovascular risk profiles than rural or urban dwellers. The objective of this study was to evaluate the sex differences with specific cardiovascular risk factors in rural-to-urban migrants.

Methods and Results

We used the rural-to-urban migrant group of the PERU MIGRANT cross-sectional study to investigate the sex differences in specific cardiovascular risk factors: obesity, hypertension, metabolic syndrome, as well as exposures of socioeconomic status, acculturation surrogates and behavioral characteristics. Logistic regression analysis was used to characterize strength of association between sex and our outcomes adjusting for potential confounders. The sample of migrants was 589 (mean age 46.5 years) and 52.4% were female. In the adjusted models, women were more likely to be obese (OR=5.97; 95%CI: 3.21–11) and have metabolic syndrome (OR=2.22; 95%CI: 1.39–3.55) than men, explaining the greatest variability for obesity and metabolic syndrome but not for hypertension.

Conclusions

Our results suggest that interventions for CVD in Peru should be sex-specific and address the unique health needs of migrant populations living in urban shantytowns since the risk factors for obesity and metabolic syndrome differ between males and females.     

Hypertriglyceridemia and waist circumference predict cardiovascular risk among HIV patients: a cross-sectional study

Background

Although half of HIV-infected patients develop lipodystrophy and metabolic complications, there exists no simple clinical screening tool to discern the high from the low-risk HIV-infected patient. Thus, we evaluated the associations between waist circumference (WC) combined with triglyceride (TG) levels and the severity of lipodystrophy and cardiovascular risk among HIV-infected men and women.

Methods

1481 HIV-infected men and 841 HIV-infected women were recruited between 2005 and 2009 at the metabolic clinic of the University of Modena and Reggio Emilia in Italy. Within each gender, patients were categorized into 4 groups according to WC and TG levels. Total and regional fat and fat-free mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed tomography. Various cardiovascular risk factors were assessed in clinic after an overnight fast.

Results

The high TG/high WC men had the most VAT (208.0±94.4 cm²), as well as the highest prevalence of metabolic syndrome (42.2%) and type-2 diabetes (16.2%), and the highest Framingham risk score (10.3±6.5) in comparison to other groups (p<0.05 for all). High TG/high WC women also had elevated VAT (150.0±97.9 cm²) and a higher prevalence of metabolic syndrome (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk score(2.9±2.8) by comparison to low TG/low WC women (p<0.05 for all).

Conclusions

A simple tool combining WC and TG levels can discriminate high- from low-risk HIV-infected patients.     

NSAID use selectively increases the risk of non-fatal myocardial infarction: a systematic review of randomised trials and observational studies

Background

Recent clinical trials and observational studies have reported increased coronary events associated with non steroidal anti-inflammatory drugs (NSAIDs). There appeared to be a disproportionate increase in non-fatal versus fatal events, however, numbers of fatal events in individual studies were too small, and event rates too low, to be meaningful.

Objectives

We undertook a pooled analysis to investigate the effect of NSAIDs on myocardial infarction (MI) risk with the specific aim to differentiate non-fatal from fatal events.

Methods

We searched Pubmed (January, 1990 to March, 2010) for observational studies and randomised controlled trials that assessed the effect of NSAIDs (traditional or selective COX-2 inhibitors [coxibs]) on MI incidence separately for fatal and non-fatal events. Summary estimates of relative risk (RR) for non-fatal and fatal MIs were calculated with a random effects model.

Results

NSAID therapy carried a RR of 1.30 (95% CI, 1.20–1.41) for non-fatal MI with no effect on fatal MI (RR 1.02, 95% CI, 0.89–1.17) in six observational studies. Overall, the risk increase for non-fatal MI was 25% higher (95% CI, 11%–42%) than for fatal MI. The two studies that included only individuals with prior cardiovascular disease presented risk estimates for non-fatal MI on average 58% greater (95% CI, 26%–98%) than those for fatal MI. In nine randomised controlled trials, all investigating coxibs, the pooled RR estimate for non-fatal MI was 1.61 (95% CI, 1.04–2.50) and 0.86 (95% CI 0.51–1.47) for fatal MIs.

Conclusions

NSAID use increases the risk of non-fatal MI with no substantial effect on fatal events. Such differential effects, with potentially distinct underlying pathology may provide insights into NSAID-induced coronary pathology. We studied the association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of myocardial infarction (MI), separating non-fatal from fatal events, summarizing the evidence from both observational studies and randomised controlled trials. An increased risk of non-fatal MI was clearly found in both types of studies while use of NSAID did not confer an increased risk of fatal MI. Our findings provide support for the concept that thrombi generated under NSAID treatment could be different from spontaneous thrombi.     

Psoriasis and hypertension severity: results from a case-control study

Background

Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized.

Objective

We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients.

Approach

We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients.

Key Results

Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p<0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p<0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68–13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01–24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58–37.33) in multivariable analysis after adjusting for traditional cardiac risk factors.

Conclusions

Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients.     

Risk of severe knee and hip osteoarthritis in relation to level of physical exercise: a prospective cohort study of long-distance skiers in Sweden

Background

To complete long-distance ski races, regular physical exercise is required. This includes not only cross-country skiing but also endurance exercise during the snow-free seasons. The aim of this study was to determine whether the level of physical exercise is associated with future risk of severe osteoarthritis independent of previous diseases and injuries.

Methodology/Principal Findings

We used a cohort that consisted of 48 574 men and 5 409 women who participated in the 90 km ski race Vasaloppet at least once between 1989 and 1998. Number of performed races and finishing time were used as estimates of exercise level. By matching to the National Patient Register we identified participants with severe osteoarthritis, defined as arthroplasty of knee or hip due to osteoarthritis. With an average follow-up of 10 years, we identified 528 men and 42 women with incident osteoarthritis. The crude rate was 1.1/1000 person-years for men and 0.8/1000 person-years for women. Compared with racing once, participation in ≥5 races was associated with a 70% higher rate of osteoarthritis (multivariable-adjusted hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.33 to 2.22). The association was dose-dependent with an adjusted HR of 1.09, 95% CI 1.05 to 1.13 for each completed race. A faster finishing time, in comparison with a slow finishing time, was also associated with an increased rate (adjusted HR 1.51, 95% CI 1.14 to 2.01). Contrasting those with 5 or more ski races and a fast finish time to those who only participated once with a slow finish time, the adjusted HR of osteoarthritis was 2.73, 95% CI 1.78 to 4.18.

Conclusions/Significance

Participants with multiple and fast races have an increased risk of subsequent arthroplasty of knee and hip due to osteoarthritis, suggesting that intensive exercise may increase the risk.     

Marital status and mortality among middle age and elderly men and women in urban Shanghai

Background

Previous studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality.

Methods

We examined the association of marital status with mortality using data from the Shanghai Women''s Health Study (1996–2009) and Shanghai Men''s Health Study (2002–2009), two population-based cohort studies of 74,942 women aged 40–70 years and 61,500 men aged 40–74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI).

Results

Unmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality.

Conclusions

Marriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women.     

Paternal and maternal history of myocardial infarction and cardiovascular diseases incidence in a Dutch cohort of middle-aged persons

Background

A positive parental history of myocardial infarction (MI) is an independent risk factor for cardiovascular diseases (CVD). However, different definitions of parental history have been used. We evaluated the impact of parental gender and age of onset of MI on CVD incidence.

Methods

Baseline data were collected between 1993 and 1997 in 10 524 respondents aged 40–65 years. CVD events were obtained from the National Hospital Discharge Register and Statistics Netherlands. We used proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for CVD incidence and adjusted for lifestyle and biological risk factors.

Results

At baseline, 36% had a parental history of MI. During 10-year follow-up, 914 CVD events occurred. The age and gender adjusted HR was 1.3 (95% CI 1.1–1.5) for those with a paternal MI, 1.5 (1.2–1.8) for those with a maternal MI and 1.6 (1.2–2.2) for those with both parents with an MI. With decreasing parental age of MI, HR increased from 1.2 (1.0–1.6) for age ≥70 years to 1.5 (1.2–1.8) for age <60 years for a paternal MI and from 1.1 (0.9–1.5) to 2.2 (1.6–3.0) for a maternal MI. The impact of having a mother with MI before age 60 significantly differed in women [(2.9 (1.8–4.6)] and men [1.5 (0.9–2.6)]. Adjustment only slightly influenced HRs for maternal MI.

Conclusions

Respondents with a parental history of MI have an increased CVD incidence, in particular with parental onset of MI before age 70. A maternal history of MI before age 60 was the strongest predictor of CVD incidence.     

Oxidative stress in human hypertension: association with antihypertensive treatment, gender, nutrition, and lifestyle

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension. Our aim was to measure markers of oxidative stress in hypertensive subjects, and assess the potential confounding influences of antihypertensive therapy, other cardiovascular risk factors, gender, lifestyle, and nutrition. Markers of oxidative stress, including plasma and 24 h urinary F2-isoprostanes, were measured in 70 untreated (men = 43, women = 27) and 85 treated (men = 43, women = 42) hypertensive subjects and 40 normotensive controls (men = 20, women = 20). Overall, F2-isoprostanes were not elevated in hypertensive subjects compared with controls. However, urinary and plasma F2-isoprostanes were significantly lower in treated compared with untreated hypertensive men, but not women. In hypertensive men, the number of antihypertensive drugs taken was inversely associated with both urinary and plasma F2-isoprostanes (p <.05). Self-reported alcohol intake and biomarkers of alcohol consumption (gamma-glutamyl transpeptidase and high-density lipoprotein cholesterol) were positively associated with plasma but not urinary, F2-isoprostanes in men. Several nutrients were independently associated with plasma and urinary F2-isoprostanes in women. The results do not support the hypothesis that treated or untreated hypertensive subjects are under increased oxidative stress compared with normotensive controls.     

AGT M235T genotype/anxiety interaction and gender in the HyperGEN study

Background

Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups.

Methodology

The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style).

Principal Findings

Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype.

Conclusion/Significance

The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.     

Sedentary behaviour and biomarkers for cardiovascular disease and diabetes in mid-life: the role of television-viewing and sitting at work

Background

Knowledge of sedentary behaviour associations with health has relied mainly on television-viewing as a proxy and studies with other measures are less common. To clarify whether sedentary behaviour is associated with disease-risk, we examined associations for television-viewing and sitting at work.

Methods

Using the 1958 British birth cohort (n = 7660), we analysed cross-sectional associations between television-viewing and work sitting (four categories, 0–1 to ≥3 h/d) with total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)-cholesterol, triglycerides, blood pressure, glycated haemoglobin, fibrinogen, C-reactive protein, hypertension and metabolic syndrome at 45 y. We adjusted for lifestyle and socio-demographic factors and assessed mediation of associations by body mass index (BMI) and diet. We also assessed whether the sedentary indicators are related similarly to factors linked to disease-risk.

Results

There was a general trend of adverse socio-demographic and lifestyle characteristics with higher h/d television-viewing, but trends in the opposite direction for work sitting. Television-viewing was associated with most biomarkers and associations were mediated by BMI: e.g. for each category increase in television-viewing, HDL-cholesterol in men was lower by 2.3% (95% CI: 1.5%, 3.2%) and, in BMI and diet adjusted analyses, by 1.6% (0.8%, 2.4%); for women, by 2.0% (1.2%, 2.9%) and 0.9% (0.1%, 1.6%) respectively. Few, weaker associations for work sitting were found, in men only: e.g. corresponding values for HDL-cholesterol were 1.2% (0.5%, 1.9%) and 0.9% (0.3%, 1.5%). Odds for metabolic syndrome were elevated by 82% and 33% respectively for men watching television or work sitting for ≥3 vs. 0–1 h/d.

Conclusions

Associations with cardiovascular disease and diabetes biomarkers in mid-adulthood differed for television-viewing and work sitting. The role of sedentary behaviour may vary by leisure and work domains or the two indicators reflect differing associations with other disease-related influences.     

Is Human Cytomegalovirus Infection Associated with Hypertension? The United States National Health and Nutrition Examination Survey 1999–2002

Purpose

Recent studies have implicated the human cytomegalovirus (HCMV) as a possible pathogen for causing hypertension. We aimed to study the association between HCMV infection and hypertension in the United States National Health and Nutrition Examination Survey (NHANES).

Methods

We analyzed data on 2979 men and 3324 women in the NHANES 1999–2002. We included participants aged 16–49 years who had valid data on HCMV infection and hypertension.

Results

Of the participants, 54.7% had serologic evidence of HCMV infection and 17.5% had hypertension. There were ethnic differences in the prevalence of HCMV infection (P<0.001) and hypertension (P<0.001). The prevalence of both increased with age (P<0.001). Before adjustment, HCMV seropositivity was significantly associated with hypertension in women (OR = 1.63, 95% CI = 1.25–2.13, P = 0.001) but not in men. After adjustment for race/ethnicity, the association between HCMV seropositivity and hypertension in women remained significant (OR = 1.55, 95% CI = 1.20–2.02, P = 0.002). Further adjustment for body mass index, diabetes status and hypercholesterolemia attenuated the association (OR = 1.44, 95% CI = 1.10–1.90, P = 0.010). However, after adjusting for age, the association was no longer significant (OR = 1.24, 95% CI = 0.91–1.67, P = 0.162).

Conclusions

In this nationally representative population-based survey, HCMV seropositivity is associated with hypertension in women in the NHANES population. This association is largely explained by the association of hypertension with age and the increase in past exposure to HCMV with age.     

Time course and pattern of metastasis of cutaneous melanoma differ between men and women

Background

This study identified sex differences in progression of cutaneous melanoma.

Methodology/Principal Findings

Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7% of men and 29.2% of women (P<0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3% of men and 23.2% of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95% CI: 1.0–1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95% CI: 4.2–7.1 for distant metastasis vs. satellite/in-transit recurrence, P<0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4–2.5) for men compared with 15.3% (95% CI: 11.1–19.5; P = 0.008) for women.

Conclusions/Significance

Both, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic factors may be responsible for these sex differences.