Reduction In Cardiovascular Disease Events Research Articles

Cardiovascular Protection in People With Diabetes.

Cardiovascular Protection in People With Diabetes.

Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events?

Background:Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD).Objective:In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events.Results:In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels.Conclusion:Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy.

Abstract 038: 30-year Risk of Cardiovascular Disease in Adolescents With Severe Obesity: Benefit of Bariatric Surgery (Teen-LABS)

Severe obesity in youth is associated with accentuated risks of chronic health problems. However, quantifying risk of cardiovascular disease (CVD) events later in life is challenged by long latent periods between risk factor development and overt disease outcomes. A 30-year CVD event risk score has been developed in the Framingham Offspring cohort to address this problem. The 30-year CVD event risks were estimated for adolescents with severe obesity prior to and up to 5 years after undergoing bariatric surgery. We hypothesized that adolescents with severe obesity would be at high risk for full CVD events within 30-years and that bariatric surgery would reduce that risk. Adolescents (n=215; mean age pre-op = 17 years; mean body mass index (BMI) = 53 kg/m 2 ) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) were used in this analysis. Data collected preoperatively and annually to 5 years were analyzed. A 30-year composite risk score (CVD event risk) was examined which included the following hard endpoints: coronary death, myocardial infarction, and stroke (fatal and nonfatal), coronary insufficiency, angina pectoralis, transient ischemic attack, intermittent claudication, and congestive heart failure. CVD event risk score requires the following risk factors for calculation: Sex, age, systolic blood pressure, antihypertensive treatment, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and BMI. Data are presented as mean (SD) with differences between time-points examined using linear mixed-models. Preoperatively, the likelihood of CVD events was 7.9 (6.7)%. Preoperatively, 52.6% of the cohort presented with >5% risk of CVD events, 22.3% with >10% risk of event, and 10.7% with >15% risk of event. At 1-year post-surgery a significant reduction in CVD events (7.9 [6.7]% to 4.0 [3.4]%, p<0.0001) was estimated. A reduction in proportion with >5% (52.6% to 22.1%), >10% (22.3% to 4.4%), and >15% (10.7% to 1.7%) risk of CVD events was observed. These predicted benefits for full CVD events were sustained at 2 years (4.0 [2.9]%), 3 years (4.2 [3.8]%), 4 years (4.3 [3.1]%), and 5 years (4.8 [3.8]%) post-surgery, with similar >5%, >10%, and >15% risks noted (p<0.0001 for all years versus baseline). These data suggest that prior to bariatric surgery, the risk of CVD event within 30-years is pronounced. However, following bariatric surgery, risk of hard endpoints is substantially reduced for up to 5 years following surgery.

Vitamin D Status, Supplementation and Cardiovascular Disease.

This review was conducted to assess the dose-response relationship between vitamin D and cardiovascular disease (CVD) outcomes in humans: Prospective cohort studies indicate a multivariable-adjusted non-linear increase in CVD events at levels of circulating 25-hydroxyvitamin D [25(OH)D] of less than 50 nmol/l. However, Mendelian randomization studies do not support these findings. Although meta-analyses of randomized controlled trials (RCTs) do not rule out small beneficial vitamin D effects on surrogate parameters of CVD risk, such as arterial stiffness, at vitamin D doses equivalent to 1,000-5,333 IU daily, other meta-analyses of RCTs show no reduction in CVD events by vitamin D supplementation. Notably, some cohort studies and a recent RCT provide evidence for harmful effects of vitamin D on CVD outcomes at 25(OH)D levels in excess of 100 nmol/l. In conclusion, more studies in individuals with a deficient 25(OH)D level (i.e. <30 nmol/l) are needed, but caution is necessary regarding supplementation with vitamin D doses achieving a 25(OH)D level which exceeds 100 nmol/l.

Powerful diuretics: A common denominator in landmark hypertension and type 2 diabetes mellitus trials.

Powerful diuretics: A common denominator in landmark hypertension and type 2 diabetes mellitus trials.

The challenges of proprotein convertase subtilisin-kexin-9 inhibitors for lipid guidelines and models of care.

The article reviews the challenges facing cardiovascular disease (CVD) guidelines committees. Clinical trials in high-risk populations have shown additional CVD event reduction with ezetimibe and proprotein convertase subtilisin-kexin-9 inhibitors. These trials recruit middle-aged secondary prevention populations, whereas increasingly the population at risk of CVD comprises the elderly in primary prevention. Some major guidelines have moved from a lipid-target to a risk-based approach. Some guidelines wish to preserve treatment targets to optimize the risk profile of individual patients as opposed to using population-based approaches. A numbers needed to treat approach has been suggested as a way of prioritizing patients for treatment, while retaining an individual's LDL cholesterol risk. However, the main barrier to implementation of some novel therapies in medicine is not their efficacy or safety but their cost. Health economic approaches that consider both benefits and costs can help guideline committees to define populations mostly likely to benefit. The efficacy and expense of novel treatments is challenging traditional guideline development. Previously guideline committees used only to review clinical efficacy and safety endpoints but now they also have to consider costs to derive recommendations that are practical to implement.

The effectiveness and cost-effectiveness of plant sterol or stanol-enriched functional foods as a primary prevention strategy for people with cardiovascular disease risk in England: a modeling study

This study appraises the effectiveness and cost-effectiveness of consumption of plant sterol-enriched margarine-type spreads for the prevention of cardiovascular disease (CVD) in people with hypercholesterolemia in England, compared to a normal diet. A nested Markov model was employed using the perspective of the British National Health Service (NHS). Effectiveness outcomes were the 10-year CVD risk of individuals with mild (4–6 mmol/l) and high (above 6 mmol/l) cholesterol by gender and age groups (45–54, 55–64, 65–74, 75–85 years); CVD events avoided and QALY gains over 20 years. This study found that daily consumption of enriched spread reduces CVD risks more for men and older age groups. Assuming 50% compliance, 69 CVD events per 10,000 men and 40 CVD events per 10,000 women would be saved over 20 years. If the NHS pays the excess cost of enriched spreads, for the high-cholesterol group, the probability of enriched spreads being cost-effective is 100% for men aged over 64 years and women over 74, at £20,000/QALY threshold. Probabilities of cost-effectiveness are lower at younger ages, with mildly elevated cholesterol and over a 10-year time horizon. If consumers bear the full cost of enriched spreads, NHS savings arise from reduced CVD events.

Eligibility for alirocumab or evolocumab treatment in 1090 hypercholesterolemic patients referred to a regional cholesterol treatment center with LDL cholesterol ≥70 mg/dL despite maximal-tolerated LDL-cholesterol-lowering therapy.

BackgroundProprotein convertase subtilisin/kexin type 9 inhibitors, Praluent (alirocumab [ALI]) and Repatha (evolocumab [EVO]) have been approved as adjuncts to the standard-of-care maximal-tolerated dose (MTD) of low-density lipoprotein cholesterol (LDLC)-lowering therapy (LLT), statin therapy, in heterozygous (HeFH) (ALI or EVO) or homozygous (EVO) familial hypercholesterolemia, or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient (both). Since LDLC lowering has been revolutionized by ALI and EVO, specialty pharmaceutical pricing models will be applied to a mass market.MethodsWe applied US Food and Drug Administration (FDA) and insurance eligibility criteria for ALI and EVO to 1090 hypercholesterolemic patients serially referred over 3 years who then received ≥2 months maximal-tolerated dose of standard-of-care LDL cholesterol-lowering therapy (MTDLLT) with follow-up LDLC ≥70 mg/dL. MTDLLT did not include ALI or EVO, which had not been commercially approved before completion of this study.ResultsOf the 1090 patients, 140 (13%) had HeFH by clinical diagnostic criteria and/or CVD with LDLC >100 mg/dL despite ≥2 months on MTDLLT, meeting FDA insurance criteria for ALI or EVO therapy. Another 51 (5%) patients were statin intolerant, without HeFH or CVD.ConclusionIf 13% of patients with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT are eligible for ALI or EVO, then specialty pharmaceutical pricing models (~$14,300/year) might be used in an estimated 10 million HeFH-CVD patients. Whether the health care savings arising from the anticipated reduction of CVD events by ALI or EVO justify their costs in populations with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT remains to be determined.

Antihypertensive Medication Adherence and Risk of Cardiovascular Disease Among Older Adults: A Population-Based Cohort Study.

BackgroundAntihypertension medication (antihypertensive) adherence lowers risk of cardiovascular disease (CVD); few studies have examined this association among older adults.Methods and ResultsWe assessed this association among Medicare fee‐for‐service beneficiaries aged 66 to 79 years who were newly diagnosed with hypertension and initiated on antihypertensives in 2008–2009 (n=155 597). We calculated proportion of days covered (PDC) during follow‐up, using proportional subdistribution hazard models, to examine association between antihypertensive adherence and a composite CVD outcomes, including first incident of fatal/nonfatal acute myocardial infarction, ischemic heart disease, stroke/transient ischemic attack, and heart failure. During follow‐up (median 5.8 years and 798 621 person‐years), we documented 47 198 CVD events. Among beneficiaries, 60.8%, 30.3%, and 8.9% had PDC ≥80%, 40% to 79%, and <40%. Crude incidence of CVD events were 40.1 (95% CI, 40.0–40.1), 93.9 (93.8–93.9), and 98.1 (98.1–98.2) per 1000 person‐years for PDC ≥80%, 40% to 79%, and <40%, respectively. Adjusted hazard ratios for CVD events were 1.0 (<40% as reference), 1.0 (0.97–1.03) for 40% to 79%, and 0.44 (0.42–0.45) for ≥80% (P<0.001). Dose‐response analysis suggested a nonlinear relationship between PDC and risk for CVD events with a protective effect of ≥80%. The pattern of associations between PDC and ischemic heart disease, stroke/transient ischemic attack, and heart failure were largely consistent as for CVD events and across different groups.ConclusionsAntihypertensive adherence was associated with a significantly lower risk of CVD events among older adults. There appeared to be a threshold effect in reducing CVD events at around PDC 80%, above which the risk for CVD reduced substantially.

Lipoprotein(a)-apheresis in the light of new drug developments

Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD). Recently <50 mg/dl was recommended as the desirable level for clinical use and decision making. All established medical therapies to lower cholesterol levels have no impact on lowering Lp(a) except niacin which is all too often poorly tolerated and not obtainable everywhere. Lipoprotein apheresis is an extracorporeal treatment to lower levels of Lp(a) significantly by > 60%. In some countries it is recommended in very high risk patients with early or progressive CVD. Retrospective data indicate that regular apheresis reduces cardiovascular events, which was substantiated by a recent prospective observational trial. Apheresis is very well tolerated with very few side effects, but it is expensive, time consuming, and offered by specialised centres only.To improve the overall treatment new drug therapies are required. Some of the recently approved lipid modifying drugs lower Lp(a) in addition to LDL-cholesterol: Mipomersen ∼ 25%, CETP-inhibitors ∼ 50%, PCSK9-inhibitors ∼ 30%. If the Lp(a) lowering effect contributes to the expected reduction of CVD events has to be shown in the future. The apo(a) antisense oligonucleotide is the only approach to specifically lower Lp(a). A phase 1 trial showed a decrease in a dose dependant manner (up to 88.8%) in healthy volunteers.Despite the lack of prospective randomised trials apheresis these days remains the standard of care in patients with elevated Lp(a) and severe CVD.

Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in Patients With Hypertension: SPRINT (Systolic Blood Pressure Intervention Trial).

It is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of left ventricular hypertrophy (LVH) in patients with hypertension and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population. This analysis included 8164 participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP <120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead ECGs recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjustment for LVH as a time-varying covariate. Among SPRINT participants without baseline LVH (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (versus standard) BP lowering were 66% more likely to regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31-2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (hazard ratio of intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64-0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment for LVH as a time-varying covariate, respectively). Among patients with hypertension but no diabetes mellitus, intensive BP lowering (target systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP <140 mm Hg) resulted in lower rates of developing new LVH in those without LVH and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Visit-to-visit SBP variability and cardiovascular disease in a multiethnic primary care setting: 10-year retrospective cohort study.

The current study aims to determine the relationship of long-term visit-to-visit variability of SBP to cardiovascular disease (CVD) in a multiethnic primary care setting. This is a retrospective study of a cohort of 807 hypertensive patients over a period of 10 years. Three-monthly clinic blood pressure readings were used to derive blood pressure variability (BPV), and CVD events were captured from patient records. Mean age at baseline was 57.2 ± 9.8 years with 63.3% being women. The BPV and mean SBP over 10 years were 14.7 ± 3.5 and 142 ± 8 mmHg, respectively. Prevalence of cardiovascular event was 13%. In multivariate logistic regression analysis, BPV was the predictor of CVD events, whereas the mean SBP was not independently associated with cardiovascular events in this population. Those with lower SBP and lower BPV had fewer cardiovascular events than those with the same low mean SBP but higher BPV (10.5 versus 12.8%). Similarly those with higher mean SBP but lower BPV also had fewer cardiovascular events than those with the same high mean and higher BPV (11.6 versus 16.7%). Other variables like being men, diabetes and Indian compared with Chinese are more likely to be associated with cardiovascular events. BPV is associated with an increase in CVD events even in those who have achieved lower mean SBP. Thus, we should prioritize not only control of SBP levels but also BPV to reduce CVD events further.

Wearable technology to reduce sedentary behavior and CVD risk in older adults: design of a randomized controlled trial.

Persons aged over 65 years account for over the vast majority of healthcare expenditures and deaths attributable to cardiovascular disease (CVD). Accordingly, reducing CVD risk among older adults is an important public health priority. Structured physical activity (i.e. exercise) is a well-documented method of decreasing CVD risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk populations of older adults. Thus adjuvant strategies appear necessary to reduce CVD risk. Accumulating evidence indicates that prolonged sedentary behavior (e.g. sitting) has detrimental health effects that are independent of engagement in recommended levels of moderate-intensity exercise. Yet clinical trials in this area are lacking. We hypothesize that exercise, when combined with a novel technology based intervention specifically designed to reduce sedentary behavior will reduce CVD risk among sedentary older adults. The purpose of this study is to evaluate the feasibility and efficacy of combining a traditional, structured exercise intervention with an innovative intervention designed to decrease sedentary behavior and increase non-exercise physical activity (NEPA). This study will provide us with critical data necessary to design and implement a full-scale trial to test our central hypothesis. Participants aged ≥60 years with moderate to high risk of coronary heart disease (CHD) events are randomly assigned to either the exercise and technology intervention (EX + NEPA) or exercise alone (EX) groups. Study dependent outcomes include changes in 1) daily activity patterns, 2) blood pressure, 3) exercise capacity, 4) waist circumference, and 5) circulating indices of cardiovascular function. This study will provide critical information for designing a fully-powered clinical trial, which could have health implications for the ever increasing population of older adults.

Abstract P176: Impact of Serious Adverse Event Risks on the Cost-effectiveness of Intensive Blood Pressure Goals in Patients Aged ≥75 Years

Background: Compared to the overall Systolic Blood Pressure Intervention Trial (SPRINT) results, patients aged ≥75 years at baseline had a greater reduction in cardiovascular disease (CVD) events and all-cause mortality with an intensive systolic blood pressure (SBP) goal (&lt;120 mmHg) compared to a standard SBP goal (&lt;140 mmHg). Applying an intensive SBP goal in high-risk older patients represents a major shift in clinical practice and may increase concern for medication-related severe adverse events (SAEs). We hypothesized that the benefits of reduced CVD risk would outweigh the increased costs and SAE risk of intensive vs. standard SBP goals in SPRINT-eligible patients aged ≥75 years even when considering variable SAE risks. Methods: A microsimulation health-state transition model of 10,000 patients was created to estimate the CVD events, SAEs, quality-adjusted life years (QALYs), and direct healthcare costs of intensive vs. standard SBP goals. The model assumed patients were adherent to treatment during the median SPRINT follow-up, but that all patients would become non-adherent over 5 years. While adherent, CVD and SAE risks were derived from published SPRINT effect estimates for the ≥75 subgroup. Due to uncertainty in the SAE risk associated with intensive SBP goals in older adults, the intensive arm SAE risk was varied to determine the point at which treatment costs and harms outweighed CVD benefits at accepted willingness-to-pay thresholds. Healthcare costs and health state utilities were derived from national sources and other published estimates. Results: If SAE risk was equal to the observed rates in SPRINT, mean lifetime costs and QALYs were $268,000 and 7.85 for the intensive arm, and $262,000 and 7.60 for the standard arm. The resulting incremental cost-effectiveness ratio (ICER) was about $26,000 per QALY gained. However, as SAE risk in the intensive arm increased by 1.5, 2, and 2.5 times, the ICER increased to $33,000, $43,000, and $55,000 per QALY gained, respectively. Conclusion: Intensive SBP goals may be a cost-effective way to reduce CVD events and improve survival in patients aged ≥75 years, but safety and cost-effectiveness depend on medication-related SAE risk. However, these results are based on summary data and do not account for clustering of risks at the individual patient level. Thus, more precise prediction of risks and benefits is needed to guide selection of older patients for intensive SBP treatment goals.

Statin prescribing for people with severe mental illnesses: a staggered cohort study of ‘real-world’ impacts

ObjectivesTo estimate the ‘real-world effectiveness of statins for primary prevention of cardiovascular disease (CVD) and for lipid modification in people with severe mental illnesses (SMI), including schizophrenia and bipolar disorder.DesignSeries...

Predicting and Preventing Cardiovascular Events in Asymptomatic Patients: A 10-Year Prospective Study

OBJECTIVE: Cardiovascular disease (CVD) had become a leading cause of deathamong people in developing countries including Thai military officers. No long termdata on preventing CVD events in this group had been published before.Thus, our mainstudy purposes were to identify the target individuals who carried the substantial riskof developing CVD event and prevent them in advance. MATERIALS AND METHODS: After approved by the ethics committee and medicalorganization of Chandrubeksa hospital in 2006, all in service officers (aged of 35-60years) who undergone annual screening, were voluntarily enrolled. We excluded officerswho were beyond this age range, not willing to participate or already had CVD. Topredict the 10-yr risk of developing CVD events, we used the modified Coronary RiskChart (mCRC) (available at www@thaiafheart.com) to classify asymptomatic Air Forceofficers into three groups; the low, intermediate and the high risk candidates, accordingto the predicted cardiovascular risk of 20% respectively. Forall participants, life-style modifications was given, but medication and further screeningwith exercise stress test were provided only in the intermediate and high risk groups.All subjects were followed from 2006-2016 by an annual physical check-up. After tenyears, the clinical outcomes (acute coronary syndrome, stroke, total death and compositeevents) were compared between the three groups. RESULTS: Of total 410 asymptomatic cases, 85.4% were men and had a mean age of50.9 ± 6.1 years. During 10-yr follow-up, we were able to track the health status of allparticipants. There was total of 52 events, with only 5 events (5.7%) occurring in thelow risk group (including one ACS, one ischemic stroke and 3 non-CVD deaths). Incontradiction, 47 clinical events (14.6%, p = 0.026 for comparison with the low riskgroup) were observed in the combined intermediate and high risk groups (including 7non-fatal ACS, 10 ischemic strokes, 2 CVD and 28 non-CVD deaths). Both ACS andstroke occurred less frequently than predicted rate and no statistical different of actualevents was noted in each assigned risk group. The incidence of ACS and stroke amongthe low, intermediate and high risk candidates were 1.1%, 1.1% and 3.8% and 1.1%,4.2% and 1.5% respectively. The mean time from entering the registry to the occurrenceof an ACS was 4.9 years and the mean age of ACS cases was 55.1 years. Stroke wasobserved 7.1 years on average after entering the registry. All of strokes were ischemicin origin and the mean age of stroke cases was 61.4 years. A total of 33 deaths (8%)occurred 3.4%, 7.9% and 11.3% among the low, intermediate and high risk individuals.Death occurred after on average 6.7 years at a mean age was 59.4 years. The CVD deathwas very low (6%), each of them were from STE-ACS and stroke. The non-cardiovasculardeath was 31 cases (94%). The common causes were cancer (n = 12), cirrhosis (n = 6),accident and drowning (n = 6). The death rate and composite outcome of ACS , strokeor death were significantly higher in the highest risk group when compared with thoseof the low risk candidates: relative risk of 3.6 (95%CI: 1-12.8), p = 0.04 and3.3(95%CI:1.2-9.0), p = 0.016, respectively. CONCLUSION: By using the mCRC (available at www.thaiafheart.com), predictionand reduction of CVD events in asymptomatic officers were feasible. The observed ACSand stroke rate were > 50% lower than the predicted one and no statistically significancewas found among the three risk groups. Progression to ACS or stroke was observed alsoin non-high risk cases. We therefore recommend re-assessing CV risk every 3-year andre-emphasizing the importance of CV preventive measures. While he ACS and strokerates were lower than expected, we observed the high rate of non-CVD death which wassignificantly increased in the high-risk group. This group of individuals should be targetedfor further preventive measures related e.g. smoking and alcohol consumption.

Global Risk Assessment to Guide Blood Pressure Management in Cardiovascular Disease Prevention.

Elevated blood pressure (BP) is a causal risk factor for cardiovascular disease (CVD). Epidemiological analyses have established the graded and continuous association between higher BP and CVD. Moreover, randomized clinical trials among individuals with hypertension have demonstrated, in aggregate, a reduction in CVD events by 20%, coronary heart disease (CHD) by 17%, stroke by 27%, and heart failure by 28% for every 10 mm Hg systolic BP (SBP) lowering with medical therapy.1 Therefore, prevention, detection, treatment, and control of elevated BP, and its clinical correlate hypertension, is an important public health priority and a primary target for CVD prevention. Although national health surveys have demonstrated improvements in hypertension awareness and treatment, strategic opportunities to improve the efficiency and efficacy of applying BP-lowering therapy in patients most likely to benefit remain.2 Global CVD risk assessment, using multivariable prediction models that estimate absolute CVD risk from routinely measured clinical variables, has been promulgated in several CVD prevention guidelines for cholesterol management to target the most intensive preventive therapies to those at highest absolute CVD risk.3–5 Hypertension guidelines, however, have instead relied solely on isolated BP thresholds and BP goals to guide treatment initiation and intensity. In this review, we provide a rationale for incorporating global CVD risk assessment in BP treatment decision-making and propose a framework to guide its implementation in future CVD prevention guidelines. Epidemiological analyses have firmly established that CVD is a multifactorial condition and that modest increases of several CVD risk factors can often lead to greater overall risk than a severe elevation of a …

A systematic review to assess adherence and persistence with statins

Objective: To identify and assess studies published over a 10 year period up to February 2016 which measure adherence or persistence with statins, to summarize their methods, strengths and weaknesses and to summarize evidence linking statin adherence/persistence with risk of cardiovascular events.Methods: Electronic databases and abstracts from four major cardiovascular disease conferences were searched from January 2005 to February 2016. The study selection process was performed by two reviewers working independently. Studies were included if they reported data regarding patient adherence or persistence with statins in adults with primary hypercholesterolemia, using any type of study design or length of follow-up. One reviewer extracted the study data and assessed study quality, which was checked by a second reviewer independently. Given the heterogeneity between the included studies a narrative critique and summary is presented.Results: We report on 84 real world studies which aimed to assess adherence or persistence with statins. The majority of studies concluded that good adherence/persistence was associated with reduction in cardiovascular events and mortality. In two studies high intensity statin regimens were associated with poorer patient adherence when compared to low intensity statins. Adherence and persistence with statin therapy also has an impact on hospitalization costs and other cardiovascular disease (CVD) related costs.Conclusions: Adherence and persistence are associated with a reduction in CVD events and mortality. There was limited evidence to suggest that high intensity statin regimens are associated with poorer treatment adherence when compared to lower intensity regimens. Hence, more robust studies are required to establish this association. As recommended by the 2013 ACC/AHA, 2016 ESC and several other clinical guidelines, clinicians and pharmacy managers should regularly monitor statin therapy adherence.

Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes

Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice. Eleven week old female db/db mice were fed normal mouse chow, with or without EMPA, for 5 weeks. Blood pressure (BP), HbA1c and fasting glucose were significantly increased in untreated db/db mice (DbC) (P < 0.01). EMPA treatment (DbE) improved glycemic indices (P < 0.05), but not BP (P > 0.05). At baseline, DbC and DbE had already established impaired diastolic relaxation as indicated by impaired septal wall motion (>tissue Doppler derived E′/A′ ratio) and increased left ventricular (LV) filling pressure (<E/E′ ratio). Although these abnormalities persisted throughout the study period in DbC, diastolic function improved with EMPA treatment. In DbC, myocardial fibrosis was accompanied by increased expression of profibrotic/prohypertrophic proteins, serum/glucocorticoid regulated kinase 1 (SGK1) and the epithelial sodium channel (ENaC), and the development of these abnormalities were reduced with EMPA. DbC exhibited eccentric LV hypertrophy that was slightly improved by EMPA, indicated by a reduction in cardiomyocyte cross sectional area. In summary, EMPA improved glycemic indices along with diastolic relaxation, as well as SGK1/ENaC profibrosis signaling and associated interstitial fibrosis, all of which occurred in the absence of any changes in BP.

The Biphasic Effect of Vitamin D on the Musculoskeletal and Cardiovascular System.

This narrative review summarizes beneficial and harmful vitamin D effects on the musculoskeletal and cardiovascular system. Special attention is paid to the dose-response relationship of vitamin D with clinical outcomes. In infants and adults, the risk of musculoskeletal diseases is highest at circulating 25-hydroxyvitamin D (25OHD) concentrations below 25 nmol/L and is low if 40–60 nmol/L are achieved. However, evidence is also accumulating that in elderly people the risk of falls and fractures increases again at circulating 25OHD levels > 100 nmol/L. Cohort studies report a progressive increase in cardiovascular disease (CVD) events at 25OHD levels < 50 nmol/L. Nevertheless, meta-analyses of randomized controlled trials suggest only small beneficial effects of vitamin D supplements on surrogate parameters of CVD risk and no reduction in CVD events. Evidence is accumulating for adverse vitamin D effects on CVD outcomes at 25OHD levels > 100 nmol/L, but the threshold may be influenced by the level of physical activity. In conclusion, dose-response relationships indicate deleterious effects on the musculoskeletal system and probably on the cardiovascular system at circulating 25OHD levels < 40–60 nmol/L and >100 nmol/L. Future studies should focus on populations with 25OHD levels < 40 nmol/L and should avoid vitamin D doses achieving 25OHD levels > 100 nmol/L.