Incidence of myocardial infarction in elderly men being treated with antihypertensive drugs: population based cohort study.

OBJECTIVE: To analyse the association between use of antihypertensive treatment, diastolic blood pressure, and long term incidence of ischaemic cardiac events in elderly men. DESIGN: Population based cohort study. Baseline examination in 1982-3 and follow up for up to 10 years. SETTING: Malmŏ, Sweden. SUBJECTS: 484 randomly selected men born in 1914 and living in Malmŏ during 1982. MAIN OUTCOME MEASURES: Observational comparisons of incidence rates and rate and hazard ratios of ischaemic cardiac events (myocardial infarction or death due to chronic ischaemic cardiac disease). RESULTS: The crude incidence rate of ischaemic cardiac events was higher in those subjects who were taking antihypertensive drugs than in those who were not (rate ratio 2.6 (95% confidence interval 1.7 to 3.9)). After adjustment for potential confounders (differences in baseline smoking habits, blood pressure, time since diagnosis of hypertension, ischaemic or other cardiovascular disease, hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, obesity, and raised serum creatinine concentration) this rate was reduced but still raised (hazard ratio 1.9 (1.0 to 3.7)). In men with diastolic blood pressure > 90 mm Hg, antihypertensive treatment was associated with a twofold increase in the incidence of ischaemic cardiac events (rate ratio 2.0 (1.1 to 3.6)), which vanished after adjustment for potential confounders (hazard ratio 1.1 (0.5 to 2.6)). In those subjects with diastolic blood pressure < or = 90 mm Hg, antihypertensive treatment was associated with fourfold increase in incidence (rate ratio 3.9 (2.1 to 7.1)), which remained after adjustment for potential confounders (hazard ratio 3.8 (1.3 to 11.0)). CONCLUSION: Antihypertensive treatment may increase the risk of myocardial infarction in elderly men with treated diastolic blood pressures < or = 90 mm Hg.     

Inflammatory Biomarkers as Risk Factors for Future Atrial Fibrillation. An Eleven-Year Follow-Up of 6315 Men and Women: The Tromsø Study

BackgroundInflammatory biomarkers are reported as risk factors for atrial fibrillation (AF), but their impact is uncertain.ObjectiveWe investigated the associations between inflammatory biomarkers and future AF in a large general cohort.MethodsAvailable markers were white blood cells (WBCs) with subgroups, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and osteoprotegerin (OPG). A total of 6315 men and women from a population survey in Tromsø, Norway in 1994 to 1995 were followed for a mean of 10.9 years. Mean age at baseline was 60 years. Measurements of height, weight, blood pressure, heart rate, total cholesterol, high-density lipoprotein (HDL) cholesterol, WBC count, and information on diabetes, angina, myocardial infarction, and antihypertensive treatment, were obtained at baseline. Fibrinogen, hs-CRP, and OPG were obtained at a follow-up visit. The outcome measure was first-ever AF, documented on an electrocardiogram. The Cox proportional hazards regression model was used to estimate hazard ratios of AF.ResultsIn the multivariable analysis, adjusted for traditional cardiovascular risk factors and other inflammatory biomarkers, hs-CRP was associated with AF in men only (hazard ratio = 1.14 for a 1 SD increase; 95% CI, 1.02–1.28). There was a significant increase in AF across quartiles of WBCs in men (P = 0.007) and in the total study population (P = 0.004). OPG was associated with AF in patients free of coronary heart disease at baseline. Fibrinogen and subgroups of WBCs showed no significant association with AF.ConclusionThis population-based cohort study showed that hs-CRP was independently associated with AF in men, but apparently not in women, and that patients with WBCs in the upper quartile had increased risk of AF.     

Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium

BackgroundHypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.MethodsUsing a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).ResultsAlthough drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (P_interaction > 5.0×10⁻⁸). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (P_interaction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.     

Control of blood pressure and risk of first acute myocardial infarction: Skaraborg hypertension project.

OBJECTIVE--To analyse the relation between treated blood pressure and concomitant risk factor and morbidity from acute myocardial infarction. DESIGN--Prospective longitudinal study. Treated blood pressures and other variables were used to predict acute myocardial infarction. SETTING--Primary health care in Skaraborg, Sweden. SUBJECTS--1121 men and 1453 women aged 40-69 years at registration at outpatient clinics, 1977-81, with no evidence of previous myocardial infarction were followed up for an average of 7.4 years. Subjects were undergoing treatment with drugs to lower blood pressure or had blood pressure that exceeded the systolic or diastolic limits, or both, for diagnosis (> 170/> 105 mm Hg (patients aged 40-60 years) and > 180/> 110 mm Hg (older than 60 years)) on three different occasions, or both. MAIN OUTCOME MEASURES--First validated event of fatal or non-fatal acute myocardial infarction. RESULTS--In men but not in women there was a negative relation between treated diastolic blood pressure and risk of acute myocardial infarction. Left ventricular hypertrophy and smoking were contributory risk factors in both sexes, as was serum cholesterol concentration in men. In men with normal electrocardiograms (n = 345) risk increased with increasing diastolic blood pressure (P = 0.047), whereas the opposite was found in men with electrocardiograms suggesting ischaemia or hypertrophy, or both (n = 499, P = 0.009). In those with a reading of 95-99 mm Hg the relative risk was 0.30 (P = 0.034); at > or = 100 mm Hg it was 0.37 (P = 0.027). No similar relations were seen in women or for systolic blood pressure. CONCLUSION--It may be hazardous to lower diastolic blood pressure below 95 mm Hg in hypertensive men with possible ischaemia or hypertrophy, or both. Electrocardiographic findings should be considered when treatment goals are decided for men with hypertension.     

Acute myocardial infarction in women: survival analysis in first six months.

OBJECTIVE--To examine the influence that being female has on the outcome of acute myocardial infarction. DESIGN--Observational follow up study. SETTING--London district general hospital. PATIENTS--216 women and 607 men with acute myocardial infarction admitted to a coronary care unit from 1 January 1988 to 31 December 1992. MAIN OUTCOME MEASURES--All cause mortality and recurrent ischaemic events in the first six months. RESULTS--Event free survival (95% confidence interval) at six months was 63.3% (56.3% to 69.4%) in women and 76.1% (72.4% to 79.4%) in men, P < 0.001. The difference was confined to the first 30 days but thereafter the hazard plots for women and men converged, with reduction of the hazard ratio from 2.36 (1.70 to 3.27) to 0.81 (0.44 to 1.48). Women were older, but their excess risk persisted after adjustment for age, other baseline variables, and indices of severity of infarction (hazard ratio 1.53 (1.09 to 2.15), P = 0.015). Women tended to be treated with thrombolysis less commonly than men but the difference was small. Substantially fewer women than men, however, were discharged taking beta blockers (23.3% v 41.4%, P < 0.001), and although additional adjustment for discharge treatment did not further reduce the point estimate of the hazard ratio (1.84 (0.89-3.83)), the 95% confidence interval was wide and statistical significance was lost. CONCLUSIONS--Women with acute myocardial infarction have a worse prognosis than men but the excess risk is confined to the first 30 days and is only partly explained by age and other baseline variables. The tendency for women to receive less vigorous treatment than men must be remedied before gender can be considered to be an independent determinant of risk.     

Survival in treated hypertension: follow up study after two decades

Objective: To compare survival and cause specific mortality in hypertensive men with non-hypertensive men derived from the same random population, and to study mortality and morbidity from cardiovascular diseases in the hypertensive men in relation to effects on cardiovascular risk factors during 22-23 years of follow up. Design: Prospective, population based observational study. Subjects and methods: 686 hypertensive men aged 47-55 at screening compared with 6810 non-hypertensive men. The hypertensive men were having stepped care treatment with either β adrenergic blocking drugs, thiazide diuretics, or combination treatment. Mortality, morbidity, and adverse effects were registered at yearly examinations and from death certificates. Main outcome measures: All cause mortality and cause specific mortality. Results: Treated hypertensive men had significantly impaired probability of total survival as well as survival from coronary heart disease and stroke. All cause mortality as well as coronary heart disease and stroke mortality were very similar in hypertensive men and normotensive men during the first decade, but increased steadily thereafter despite continuous good blood pressure control. Smoking, signs of target organ damage, and high serum cholesterol levels, but not blood pressure at screening, were significantly related to the incidence of coronary heart disease during follow up. In time dependent Cox’s regression analysis, the incidence of coronary heart disease was significantly related only to serum cholesterol concentrations in the study. Cancer mortality was almost similar in treated hypertensive men (61/686, 8.9%) and non-hypertensive men (732/6810, 10.8%). Conclusion: Treated hypertensive men had impaired survival and increased mortality from cardiovascular disease compared with non-hypertensive men of similar age. These differences were observed during the second decade of follow up. During an observation period of 22-23 years—about 15 000 patient years—hypertensive men receiving diuretics and β blockers had no increased risk of cancer or non-cardiovascular disease.

Key messages

• Hypertension is a prevalent (10-20%) and important risk factor for cardiovascular disease.
• In controlled trials over 3-5 years drug treatment for hypertension prevents these complications, but little is known about long term prognosis
• During 20-22 years treated hypertensive men had a significantly increased mortality, especially from coronary heart disease, compared with non-hypertensive men from the same population
• The high incidence of myocardial infarction was related to organ damage, smoking, and cholesterol at the time of entry to the study, and to achieved serum cholesterol concentrations during follow up
• The poor prognosis for mortality from coronary heart disease is dependent upon strict monitoring of serum cholesterol concentrations

     

Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland.

OBJECTIVE: To examine the association between plasma vitamin C concentrations and the risk of acute myocardial infarction. DESIGN: Prospective population study. SETTING: Eastern Finland. SUBJECTS: 1605 randomly selected men aged 42, 48, 54, or 60 who did not have either symptomatic coronary heart disease or ischaemia on exercise testing at entry to the Kuopio ischaemic heart disease risk factor study in between 1984 and 1989. MAIN OUTCOME MEASURES: Number of acute myocardial infarctions; fasting plasma vitamin C concentrations at baseline. RESULTS: 70 of the men had a fatal or non-fatal myocardial infarction between March 1984 and December 1992.91 men had vitamin C deficiency (plasma ascorbate < 11.4 mumol/l, or 2.0 mg/l), of whom 12 (13.2%) had a myocardial infarction; 1514 men were not deficient in vitamin C, of whom 58 (3.8%) had a myocardial infarction. In a Cox proportional hazards model adjusted for age, year of examination, and season of the year examined (August to October v rest of the year) men who had vitamin C deficiency had a relative risk of acute myocardial infarction of 3.5 (95% confidence interval 1.8 to 6.7, P = 0.0002) compared with those who were not deficient. In another model adjusted additionally for the strongest risk factors for myocardial infarction and for dietary intakes of tea fibre, carotene, and saturated fats men with a plasma ascorbate concentration < 11.4 mumol/l had a relative risk of 2.5 (1.3 to 5.2, P = 0.0095) compared with men with higher plasma vitamin C concentrations. CONCLUSIONS: Vitamin C deficiency, as assessed by low plasma ascorbate concentration, is a risk factor for coronary heart disease.     

Energy Dense,Protein Restricted Diet Increases Adiposity and Perturbs Metabolism in Young,Genetically Lean Pigs

Animal models of obesity and metabolic dysregulation during growth (or childhood) are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12), containing 15% tallow, 35% refined sugars and 9.1–12.9% crude protein, or a control corn-based diet (n = 11) with 12.2–19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (P<0.001) energy per kg body weight. At wk 15, pigs were subjected to an oral glucose tolerance test (OGTT); blood glucose increased (P<0.05) in control pigs and returned to baseline levels within 60 min. HED pigs were hyperglycemic at time 0, and blood glucose did not return to baseline (P = 0.01), even 4 h post-challenge. During OGTT, glucose area under the curve (AUC) was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001). Chronic HED intake increased (P<0.05) subcutaneous, intramuscular, and perirenal fat deposition, and induced hyperglycemia, hypoinsulinemia, and low-density lipoprotein hypercholesterolemia. A subset of HED pigs (n = 7) was transitioned back to a control diet for an additional six weeks. These pigs were subjected to an additional OGTT at 22 wk. Glucose AUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs.     

Likelihood and Predictors of ST-Elevation in Patients Hospitalized for Myocardial Infarction

Importance

Emergency treatment options in myocardial infarction are guided by presence or absence of ST-elevations in electrocardiography. Occurrence and factors associated with ST-presentation in different population groups are however inadequately known.

Objective

To determine likelihood and patient features associated with ST-elevations in myocardial infarction.

Design

Nationwide registry study including 22 hospitals with angiolaboratory during an eight year period in Finland.

Setting

Hospitalized care.

Participants

68,162 consecutive patients aged ≥30 with myocardial infarction.

Measures

Likelihood and patient features associated with presence of ST-elevations.

Results

Myocardial infarction presented with ST-elevation in 37.5% (CI 37.0–37.9%) and without in 62.5% (CI 61.9–63.1%) of patients, p<0.0001. Majority of patients aged 30–59 years with myocardial infarction had ST-elevation, but among octogenarians ST-elevations were present in only 24.7%. Presence of ST-elevations decreased with age by estimated 15.6% (CI 15.0–16.2%) per 10 year increase (p<0.0001). Men aged 40–79 years had significantly higher rate for ST-elevation myocardial infarction compared to women. Sex-based difference in presentation of myocardial infarction declined with increasing age. Overall, men had a 13% (CI 11–15%, p<0.0001) higher relative risk for ST-elevations compared to women when adjusted for age and co-morbidities. Diabetes, atrial fibrillation, peripheral or cerebral artery disease, chronic pulmonary disease, malignancy, and renal insufficiency were associated with absence of ST-elevations in myocardial infarction in multivariate analysis.

Conclusions and Relevance

Myocardial infarction presents with ST-elevations more commonly in men. Presence of ST-elevations decreases with increasing age. Diabetes, atrial fibrillation, peripheral or cerebral artery disease, chronic pulmonary disease, malignancy, and renal insufficiency are associated with absence of ST-elevations in myocardial infarction. These findings may help to predict likelihood of ST-elevations in a patient with myocardial infarction.     

The weight lowering effect of sibutramine and its impact on serum lipids in cardiovascular high risk patients with and without type 2 diabetes mellitus - an analysis from the SCOUT lead-in period

Background

Insulin responses and insulin levels seem to decline with age. However, the question of beta cell impairment attributable to ageing has been sparsely addressed in population-based studies. Non-fasting insulin levels are determined by the ambient degree of insulin resistance together with the capacity of beta cells to compensate by insulin secretion to prevent hyperglycaemia. A raised proinsulin-to-insulin ratio (proinsulin/insulin) due to impaired processing of proinsulin is an early marker of beta cell dysfunction. We hypothesised that in a general population, signs of beta cell failure with advancing age manifest not only by decreases in random insulin, but also with a corresponding increase in its precursor proinsulin.

Methods

In the Tromsø Study 1994-95 we measured insulin and proinsulin concentrations in random blood samples from 6212 persons without self-reported diabetes mellitus and plotted the levels as percentiles according to age. In regression analyses we assessed the relationships between age and insulin, proinsulin, and proinsulin/insulin, while adjusting for the concomitant measurements of glucose and other metabolic variables, and the time since the last meal.

Results

Median insulin concentrations declined significantly with advancing age group in men, but not in women. Proinsulin levels and proinsulin/insulin increased across age groups in both genders. After adjustment, greater age was associated with lower log₁₀(insulin) and higher log₁₀(proinsulin) and log₁₀(proinsulin/insulin) (p = 0.0001 for all).

Conclusions

Negative associations of age with random insulin levels, together with positive associations of age with proinsulin and proinsulin/insulin, point towards a loss of beta cell function inherent in the ageing process.     

Do antihypertensive drugs precipitate diabetes?

A longitudinal population study of 1462 women aged 38-60 was carried out from 1968-9 to 1980-1 in Gothenburg, Sweden. The initial and follow up examinations included questions concerning history of diabetes and antihypertensive treatment. A considerably increased risk of developing diabetes was observed for subjects with hypertension taking diuretics (895 patient years), subjects taking beta blockers (682 patient years), and subjects taking a combination of diuretics and beta blockers (281 patient years) compared with subjects not taking antihypertensive drugs (13 855 control years). When diuretics and beta blockers were compared no difference was found in relative risk. Despite this increased risk, and because little is known about the relation between other forms of antihypertensive treatment and diabetes, diuretics and beta blockers should remain the treatments of choice in arterial hypertension.     

Both Fasting and Glucose-Stimulated Proinsulin Levels Predict Hyperglycemia and Incident Type 2 Diabetes: A Population-Based Study of 9,396 Finnish Men

Background

Hyperproinsulinemia is an indicator of β-cell dysfunction, and fasting proinsulin levels are elevated in patients with hyperglycemia. It is not known whether proinsulin levels after a glucose load are better predictors of hyperglycemia and type 2 diabetes than fasting proinsulin.

Methods

Participants were 9,396 Finnish men (mean±SD, age 57.3±7.1 years, BMI 27.0±4.0 kg/m²) of the population-based METabolic Syndrome In Men Study who were non-diabetic at the recruitment, and who participated in a 6-year follow-up study. Proinsulin and insulin levels were measured in the fasting state and 30 and 120 min after an oral glucose load. Area under the curve (AUC) and proinsulin to insulin ratios were calculated.

Results

Fasting proinsulin, proinsulin at 30 min and proinsulin AUC during the first 30 min of an oral glucose tolerance test significantly predicted both the worsening of hyperglycemia and type 2 diabetes after adjustment for confounding factors. Further adjustment for insulin sensitivity (Matsuda index) or insulin secretion (Disposition index) weakened these associations. Insulin sensitivity had a major impact on these associations.

Conclusion

Our results suggest that proinsulin in the fasting state and after an oral glucose load similarly predict the worsening of hyperglycemia and conversion to type 2 diabetes.     

Comparison of thiazide‐like diuretics versus thiazide‐type diuretics: a meta‐analysis

Thiazide diuretics are widely used for the management of hypertension. In recent years, it has been actively debated that there is interchangeability of thiazide‐type diuretics hydrochlorothiazide and thiazide‐like diuretics including indapamide and chlorthalidone for the treatment of hypertension. With the purpose of seeking out the best thiazide diuretic for clinicians, we summarized the existing evidence on the two types of drugs and conducted a meta‐analysis on their efficacy in lowering blood pressure and effects on blood electrolyte, glucose and total cholesterol. Twelve trials were identified: five based on the comparison of indapamide versus hydrochlorothiazide and seven based on the chlorthalidone versus hydrochlorothiazide. In the meta‐analysis of blood pressure reduction, thiazide‐like diuretics seemed to further reduce systolic BP ([95% CI]; ?5.59 [?5.69, ?5.49]; P < 0.001) and diastolic BP ([95% CI]; ?1.98 [?3.29, ?0.66]; P = 0.003). Meanwhile, in the analysis of side effects, the incidence of hypokalemia ([95% CI]; 1.58 [0.80, 3.12]; P = 0.19), hyponatremia ([95% CI]; ?0.14 [?0.57, 0.30], P = 0.54), change of blood glucose ([95% CI];0.13 [?0.16, 0.41], P = 0.39) and total cholesterol ([95% CI]; 0.13 [?0.16, 0.41], P = 0.39) showed that there is no statistical significant differences between the two groups of drugs. In conclusion, using thiazide‐like diuretics is superior to thiazide‐type diuretics in reducing blood pressure without increasing the incidence of hypokalemia, hyponatraemia and any change of blood glucose and serum total cholesterol.     

Prehypertension Tsunami: A Decade Follow-Up of an Iranian Adult Population

ObjectivePrehypertension is associated with cardiovascular disease (CVD). There is no study to examine the incidence and risk factors of prehypertension in a sex stratified setting. The aim of this study was to examine the effect modification of sex for different risk factors which predicts the progression from normotension to prehypertension in a Middle East population-based cohort, during a median follow-up of 9.2 years.MethodsA multivariate Cox analysis was performed among 1466 and 2131 Iranian men and women, respectively, who were free of prehypertension, hypertension, CVD and diabetes at baseline and free of incident hypertension without preceding prehypertension at follow-up. Incident prehypertension at follow-up was defined as systolic blood pressure (SBP) of 120–139 mmHg and/or diastolic blood pressure (DBP) of 80–89 mmHg.ResultsOverall, 1440 new cases of prehypertension were identified resulting in an incidence rate of 593/10000 person-years; the corresponding values for women and men were 489/10000 and 764/10000person-years, respectively. There were significant interactions between gender with age, DBP, waist-to-hip-ratio (WHpR) and estimated glomerular filtration rate (eGFR) (all P-values <0.05) in multivariate analysis. Strong associations were found between age, body mass index (BMI) and SBP with incident prehypertension in both genders. However, the effect of DBP and WHpR was significant among women and 2-hour post challenge plasma glucose (2h-PCPG)was an independent risk factor for men. In the sex-adjusted analysis, glomerular hyperfiltration [Hazard ratio (HR) and 95%CI: 1.01 (1.00–1.01), P-value = 0.02], age, BMI, WHpR, SBP and DBP had higher risks while being female [HR (95%CI): 0.81(0.69–0.94), P-value = 0.01] had a lower risk for incident prehypertension.ConclusionAccording to this study results, among Iranian population with high incidence of prehypertension, general adiposity and glomerular hyperfiltration in total, 2h-PCPG in men and central adiposity in women should be emphasized as risk factors for prehypertension.     

Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study.

OBJECTIVE--To examine the hypothesis that a J curve relation between blood pressure and death from coronary heart disease is confined to high risk subjects with myocardial infarction. DESIGN--Cohort longitudinal epidemiological study with biennial examinations since 1950. SETTING--Framingham, Massachusetts, USA. SUBJECTS--5209 subjects in the Framingham study cohort followed up by a person examination approach. MAIN OUTCOME MEASURES--Coronary heart disease deaths and non-cardiovascular disease deaths in men and women with or without myocardial infarction relative to blood pressure. RESULTS--Among subjects without myocardial infarction non-cardiovascular disease deaths were twice to three times as common as coronary heart disease deaths. Furthermore, there was no significant relation between non-cardiovascular disease death and diastolic or systolic blood pressure. Also coronary heart disease deaths were linearly related to diastolic and systolic blood pressures. Among high risk patients (that is, people with myocardial infarction but free of congestive heart failure) death from coronary heart disease was more common than non-cardiovascular disease death. There was a significant U shaped relation between coronary heart disease death and diastolic blood pressure. Although there was an apparent U shaped relation between coronary heart disease death and systolic blood pressure, it did not attain statistical significance when controlling for age and change in systolic blood pressure from the pre-myocardial infarction level. None of the above conclusions changed when adjustments were made for risk factors such as serum cholesterol concentration, antihypertensive treatment, and left ventricular function. The U shaped relation between diastolic blood pressure and high risk subjects existed for both those given antihypertensive treatment and those not. CONCLUSIONS--These data suggest that an age and sex independent U curve relation exists for diastolic blood pressure and coronary heart disease deaths in patients with myocardial infarction but not for low risk subjects without myocardial infarction. The relation seems to be independent of left ventricular function and antihypertensive treatment.     

Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses

ObjectiveTo assess associations between baseline values of four different circulating markers of inflammation and future risk of coronary heart disease, potential triggers of systemic inflammation (such as persistent infection), and other markers of inflammation.DesignNested case-control comparisons in a prospective, population based cohort.SettingGeneral practices in 18 towns in Britain.Participants506 men who died from coronary heart disease or had a non-fatal myocardial infarction and 1025 men who remained free of such disease until 1996 selected from 5661 men aged 40-59 years who provided blood samples in 1978-1980.ResultsCompared with men in the bottom third of baseline measurements of C reactive protein, men in the top third had an odds ratio for coronary heart disease of 2.13 (95% confidence interval 1.38 to 3.28) after age, town, smoking, vascular risk factors, and indicators of socioeconomic status were adjusted for. Similar adjusted odds ratios were 1.65 (1.07 to 2.55) for serum amyloid A protein; 1.12 (0.71 to 1.77) for leucocyte count; and 0.67 (0.43 to 1.04) for albumin. No strong associations were observed of these factors with Helicobacter pylori seropositivity, Chlamydia pneumoniae IgG titres, or plasma total homocysteine concentrations. Baseline values of the acute phase reactants were significantly associated with one another (P<0.0001), although the association between low serum albumin concentration and leucocyte count was weaker (P=0.08).ConclusionIn the context of results from other relevant studies these findings suggest that some inflammatory processes, unrelated to the chronic infections studied here, are likely to be involved in coronary heart disease.     

Simulating the Impact of Improved Cardiovascular Risk Interventions on Clinical and Economic Outcomes in Russia

Objectives

Russia faces a high burden of cardiovascular disease. Prevalence of all cardiovascular risk factors, especially hypertension, is high. Elevated blood pressure is generally poorly controlled and medication usage is suboptimal. With a disease-model simulation, we forecast how various treatment programs aimed at increasing blood pressure control would affect cardiovascular outcomes. In addition, we investigated what additional benefit adding lipid control and smoking cessation to blood pressure control would generate in terms of reduced cardiovascular events. Finally, we estimated the direct health care costs saved by treating fewer cardiovascular events.

Methods

The Archimedes Model, a detailed computer model of human physiology, disease progression, and health care delivery was adapted to the Russian setting. Intervention scenarios of achieving systolic blood pressure control rates (defined as systolic blood pressure <140 mmHg) of 40% and 60% were simulated by modifying adherence rates of an antihypertensive medication combination and compared with current care (23.9% blood pressure control rate). Outcomes of major adverse cardiovascular events; cerebrovascular event (stroke), myocardial infarction, and cardiovascular death over a 10-year time horizon were reported. Direct health care costs of strokes and myocardial infarctions were derived from official Russian statistics and tariff lists.

Results

To achieve systolic blood pressure control rates of 40% and 60%, adherence rates to the antihypertensive treatment program were 29.4% and 65.9%. Cardiovascular death relative risk reductions were 13.2%, and 29.6%, respectively. For the current estimated 43,855,000-person Russian hypertensive population, each control-rate scenario resulted in an absolute reduction of 1.0 million and 2.4 million cardiovascular deaths, and a reduction of 1.2 million and 2.7 million stroke/myocardial infarction diagnoses, respectively. Averted direct costs from current care levels ($7.6 billion [in United States dollars]) were $1.1 billion and $2.6 billion, respectively.     

Applicability and cost-effectiveness of the Systolic Blood Pressure Intervention Trial (SPRINT) in the Chinese population: A cost-effectiveness modeling study

BackgroundThe Systolic Blood Pressure Intervention Trial (SPRINT) showed significant reductions in death and cardiovascular disease (CVD) risk with a systolic blood pressure (SBP) goal of <120 mm Hg compared with a SBP goal of <140 mm Hg. Our study aimed to assess the applicability of SPRINT to Chinese adults. Additionally, we sought to predict the medical and economic implications of this intensive SBP treatment among those meeting SPRINT eligibility.Methods and findingsWe used nationally representative baseline data from the China Health and Retirement Longitudinal Study (CHARLS) (2011–2012) to estimate the prevalence and number of Chinese adults aged 45 years and older who meet SPRINT criteria. A validated microsimulation model was employed to project costs, clinical outcomes, and quality-adjusted life-years (QALYs) among SPRINT-eligible adults, under 2 alternative treatment strategies (SBP goal of <120 mm Hg [intensive treatment] and SBP goal of <140 mm Hg [standard treatment]). Overall, 22.2% met the SPRINT criteria, representing 116.2 (95% CI 107.5 to 124.8) million people in China. Of these, 66.4%, representing 77.2 (95% CI 69.3 to 85.0) million, were not being treated for hypertension, and 22.9%, representing 26.6 (95% CI 22.4 to 30.7) million, had a SBP between 130 and 139 mm Hg, yet were not taking antihypertensive medication. We estimated that over 5 years, compared to standard treatment, intensive treatment would reduce heart failure incidence by 0.84 (95% CI 0.42 to 1.25) million cases, reduce CVD deaths by 2.03 (95% CI 1.44 to 2.63) million cases, and save 3.84 (95% CI 1.53 to 6.34) million life-years. Estimated reductions of 0.069 (95% CI −0.28, 0.42) million myocardial infarction cases and 0.36 (95% CI −0.10, 0.82) million stroke cases were not statistically significant. Furthermore, over a lifetime, moving from standard to intensive treatment increased the mean QALYs from 9.51 to 9.87 (an increment of 0.38 [95% CI 0.13 to 0.71]), at a cost of Int$10,997 per QALY gained. Of all 1-way sensitivity analyses, high antihypertensive drug cost and lower treatment efficacy for CVD death resulted in the 2 most unfavorable results (Int$25,291 and Int$18,995 per QALY were gained, respectively). Simulation results indicated that intensive treatment could be cost-effective (82.8% probability of being below the willingness-to-pay threshold of Int$16,782 [1× GDP per capita in China in 2017]), with a lower probability in people with SBP 130–139 mm Hg (72.9%) but a higher probability among females (91.2%). Main limitations include lack of specific SPRINT eligibility information in the CHARLS survey, uncertainty about the implications of different blood pressure measurement techniques, the use of several sources of data with large reliance on findings from SPPRINT, limited information about the serious adverse event rate, and lack of information and evidence for medication effectiveness on renal disease.ConclusionsAlthough adoption of the SPRINT treatment strategy would increase the number of Chinese adults requiring SBP treatment intensification, this approach has the potential to prevent CVD events, to produce gains in life-years, and to be cost-effective under common thresholds.

Tao Chen and colleagues estimate the cost-effectiveness of intensive blood pressure intervention in Chinese populations at high risk for cardiovascular disease.     

Comparison between liraglutide alone and liraglutide in combination with insulin on osteoporotic rats and their effect on bone mineral density

Objectives:To compare the therapeutic efficacy of liraglutide (LRG) single drug combined with insulin (Ins) on osteoporosis in rats and its effect on bone mineral density (BMD). A rat model of diabetes combined with osteoporosis was established.Methods:40 Sprague-Dawley rats were divided into four groups (blank, control, LRG and LRG+Ins). Serum levels of CrossLaps, procollagen type I N propeptide (PINP), alkaline phosphatase (AKP) and osteocalcin (BGP) were detected by ELISA. Blood glucose was measured by its reaction with glucose oxidase. Serum insulin was analyzed by radioimmunology. Bone calcium and phosphorus contents were also recorded. ELISA was used to detect inflammatory factors. Bone mineral density (BMD) measurement was also performed.Results:BMD of the control group was significantly lower than that of the other three groups (p<0.05) and BMD of the LRG + Ins group was significantly higher than that of the LRG group (p<0.05). The inflammatory factors of the control group were significantly higher than those in the other three groups (p<0.05). The inflammatory factors were negatively correlated with BMD (p<0.05).Conclusions:liraglutide in combination with insulin for the treatment of diabetes complicated with osteoporosis can reduce blood glucose in vivo, promote production of islet, effectively improve osteoporosis symptoms, increase BMD and reduce the levels of inflammatory factors in vivo.     

Association between Blood Cadmium Levels and 10-Year Coronary Heart Disease Risk in the General Korean Population: The Korean National Health and Nutrition Examination Survey 2008–2010

Background

Non-occupational heavy metals are considered risk factors for coronary heart disease (CHD). Several recent epidemiologic studies have evaluated the relationship between non-occupational cadmium exposure and risk factors for cardiovascular disease (CVD). This study was designed to investigate the relationship between non-occupational cadmium exposure and risk factors for CHD using the Framingham estimate of 10 year CHD risk.

Methods

The heavy metal dataset of the Korean National Health and Nutrition Examination Survey for 2008 through 2010, a cross-sectional survey of a representative sample of 4,668 non-institutionalized Koreans, was analyzed. Subjects were stratified into seven age groups to minimize the effects of age. The log-transformed blood cadmium concentrations were compared with the Framingham estimate of 10 year CHD risk in each age stratum.

Results

The Framingham estimate of 10 year CHD risk was significantly associated with the log-transformed blood cadmium concentrations (p<0.05) in all age groups of Korean men, with the lowest regression coefficient (0.254) for men aged 20 to <35 years and the highest (3.354) for men aged 55 to <60 years; similar results, however, were not observed in Korean women. After adjusting for survey year, age, and urinary cotinine concentration, the log-transformed blood cadmium levels among men aged 20 to <35, 40 to <45, 50 to <55, and 60 to <65 years were significantly associated with systolic blood pressure (p<0.05), but not with total and high density lipoprotein (HDL) cholesterol concentrations.

Conclusions

Cadmium exposure, even at non-occupational levels, may be associated with CHD risk in men. Despite the declines in non-occupational cadmium exposure over the past several decades, more efforts are needed.