Benefits Of Blood Pressure Reduction Research Articles

Revisiting Cardiovascular Benefits of Blood Pressure Reduction in Primary and Secondary Prevention: Focus on Targets and Residual Risk-A Systematic Review and Meta-Analysis.

Previous meta-analyses resurrected the debated statement "the lower, the better" following blood pressure (BP)-lowering treatment. We investigated the benefits of BP-lowering treatment at different BP targets by prevention category. The meta-analysis protocol was registered at the International Prospective Register of Systematic Reviews (CRD42022379249). The database included 115 BP-lowering or comparison trials from patients with (n=241 089) or without (n=198 937) previous cardiovascular events. Prevention disease groups were stratified by in-treatment achieved BP, drug class versus placebo, and drug class versus other classes. Risk ratios and 95% CIs of major adverse cardiovascular events were calculated. Following a standard (10/5 mm Hg) BP reduction, major adverse cardiovascular event relative risk reductions were not different between prevention groups (primary, 25% [95% CI, 18%-31%]; secondary, 28% [95% CI, 20%-37%]). For achieved systolic BP of at least 140 mm Hg, between 130 and 140 mm Hg, and <130 mm Hg (nadir, 125 mm Hg), (1) risk ratios of major adverse cardiovascular events and absolute risk reductions were not different between prevention groups across systolic BP strata, and (2) residual risk, though 4.1× greater in secondary than primary prevention, decreased in primary prevention from higher to lower systolic BP targets. The effect of separate drugs versus others on the primary outcome was not different between prevention groups. BP-lowering treatment benefits did not differ by prevention group to a nadir of 125 mm Hg for systolic BP. Although residual risk in secondary prevention is higher than in primary prevention, it gradually decreases at progressively lower systolic BP targets in primary prevention. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022379249.

Blood pressure and risk of venous thromboembolism: a cohort analysis of 5.5 million UK adults and Mendelian randomization studies.

Evidence for the effect of elevated blood pressure (BP) on the risk of venous thromboembolism (VTE) has been conflicting. We sought to assess the association between systolic BP and the risk of VTE. Three complementary studies comprising an observational cohort analysis, a one-sample and two-sample Mendelian randomization were conducted using data from 5 588 280 patients registered in the Clinical Practice Research Datalink (CPRD) dataset and 432 173 UK Biobank participants with valid genetic data. Summary statistics of International Network on Venous Thrombosis genome-wide association meta-analysis was used for two-sample Mendelian randomization. The primary outcome was the first occurrence of VTE event, identified from hospital discharge reports, death registers, and/or primary care records. In the CPRD cohort, 104 017(1.9%) patients had a first diagnosis of VTE during the 9.6-year follow-up. Each 20 mmHg increase in systolic BP was associated with a 7% lower risk of VTE [hazard ratio: 0.93, 95% confidence interval (CI): (0.92-0.94)]. Statistically significant interactions were found for sex and body mass index, but not for age and subtype of VTE (pulmonary embolism and deep venous thrombosis). Mendelian randomization studies provided strong evidence for the association between systolic BP and VTE, both in the one-sample [odds ratio (OR): 0.69, (95% CI: 0.57-0.83)] and two-sample analyses [OR: 0.80, 95% CI: (0.70-0.92)]. We found an increased risk of VTE with lower BP, and this association was independently confirmed in two Mendelian randomization analyses. The benefits of BP reduction are likely to outweigh the harms in most patient groups, but in people with predisposing factors for VTE, further BP reduction should be made cautiously.

To whom recommend intensive treatment for hypertension?

Arterial hypertension is the main identifiable cardiovascular risk factor, and although the benefit of blood pressure reduction is universally acknowledged, the scientific community has long been divided over the therapeutic blood pressure targets to be reached, also considering the estimated overall cardiovascular risk and the presence of individual risk factors and associated comorbidities. During the last few years, numerous clinical studies and meta-analyses, in particular, the SPRINT study, have been published, demonstrating the advantages of an intensive antihypertensive treatment, over a target blood pressure value (<140/90 mmHg), in the reduction of major cardiovascular events, myocardial infarction, stroke, heart failure, and all-causes cardiovascular mortality. Stemming from these results the major International Guidelines revisited the therapeutic objectives, recommending blood pressure value <130/80 mmHg for the vast majority of hypertensive patients until the age of 65 and suggesting a reduction of the target also in the elderly. Numerous studies and meta-analyses demonstrated that the reduction of the risk of coronary or cerebral events, and of all-causes cardiovascular mortality, is independent from the baseline value of blood pressure and the individual estimated risk. It has been also demonstrated that an early institution of antihypertensive treatment is associated with a faster realization of the recommended targets, and consequent significant benefits in terms of reduction of the incidence of myocardial infarction, heart failure, and major cardiovascular events, particularly when blood pressure control is achieved during the first 6 months of treatment, and even better during first 3 months. Other studies outlined that combination therapy with two or more drugs, mainly in a single pill configuration, are superior in reaching the recommended therapeutic targets. This is the reason why this strategy is strongly supported by the European Society of Cardiology/European Society of Hypertension (ESC/ESH) 2018 Guidelines, specifically the use of renin–angiotensin–aldosterone system inhibitors [angiotensin-converting enzyme (ACE) inhibitors and Sartans], in combination with calcium antagonist and/or thiazide diuretics, with the option to add antagonist of mineralcorticoid receptors, when an adequate blood pressure control has not been reached, or other classes of drugs, such as beta-blockers, when specific clinical indications are present, first and foremost ischaemic cardiomyopathy or heart failure. The newly proposed therapeutic goals are particularly important in high-risk patients, such as patients with previous cardiovascular events, diabetes mellitus, renal insufficiency, and patients older than 65 years of age.

Moving the Needle on Hypertension: What Knowledge Is Needed?

This review highlights the gaps in knowledge and methodological challenges discussed during the Experimental Biology 2019 expert panel session titled "Moving the Needle on Hypertension: What Knowledge Is Needed?" Hypertension is a critical public health burden. Despite a demonstrated benefit of blood pressure reduction on measures of hypertension-related morbidity and mortality, rates for successful blood pressure control remain low. Dietary sodium reduction has been shown to reduce both systolic blood pressure by approximately 3.2 mm Hg and diastolic blood pressure by 2.3 mm Hg, depending on baseline blood pressure and degree of sodium reduction. The updated Dietary Reference Intakes for adults released by the National Academies of Sciences, Engineering, and Medicine include a Chronic Disease Risk Reduction sodium intake level of 2300 mg/d, highlighting the importance of dietary sodium intake in reducing elevated blood pressure and indicating that reducing intakes to this level is expected to reduce blood pressure and risk of cardiovascular disease. The average US daily sodium intake of 3400 mg/d is well above the Chronic Disease Risk Reduction of 2300 mg/d, suggesting that dietary sodium reduction has the potential to significantly improve public health. Although the National Academies of Sciences, Engineering, and Medicine report presents intake recommendations based on a systematic, comprehensive, and thorough evaluation of the evidence, several challenges to moving the needle on hypertension remain. Success will require a more advanced understanding of sodium and potassium physiology, as well as development of the tools needed to effectively address existing research gaps and reduce barriers to sodium intake reduction.

Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study

SummaryBackgroundWorldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example.MethodsWe did a retrospective cohort study in primary care patients aged 30–79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold ≥140/90 mm Hg), or predicted 10-year cardiovascular risk alone (QRISK2 score ≥10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population.FindingsBetween Jan 1, 2011, and March 31, 2016, 1 222 670 patients in the cohort were followed up for a median of 4·3 years (IQR 2·5–5·2). 271 963 (22·2%) patients were eligible for treatment under the 2011 NICE guideline, 327 429 (26·8%) under the proposed 2019 NICE guideline, 481 859 (39·4%) on the basis of a blood pressure threshold of 140/90 mm Hg or higher, and 357 840 (29·3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32 183 patients were diagnosed with cardiovascular disease (overall rate 7·1 per 1000 person-years, 95% CI 7·0–7·2). Cardiovascular event rates in patients eligible for each strategy were 15·2 per 1000 person-years (95% CI 15·0–15·5) under the 2011 NICE guideline, 14·9 (14·7–15·1) under the proposed 2019 NICE guideline, 11·4 (11·3–11·6) with blood pressure threshold alone, and 16·9 (16·7–17·1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233 152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270 233 under the 2019 NICE guideline (29 patients), 301 523 using a blood pressure threshold (38 patients), and 322 921 using QRISK2 threshold (27 patients).InterpretationA cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided.FundingNational Institute for Health Research.

Rationale and design of a cluster randomized trial of a multifaceted intervention in people with hypertension: The Heart Outcomes Prevention and Evaluation 4 (HOPE-4) Study

BackgroundCardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated. ObjectiveThe primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels. Methods/designHOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated. SignificanceIf successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.

Global Implications of Blood Pressure Thresholds and Targets: Guideline Conversations From the World Hypertension League.

See related article, pp e13–e115 Global high blood pressure control and prevention is a major goal of the World Hypertension League (WHL), which strives to support and promote population strategies for the reduction in risks of hypertension-related outcomes. The implementation of hypertension management protocols and recommendations based on evidence from clinical studies is associated with the risk reduction in stroke, as well as cardiovascular and renal disease.1 The impact of the structured hypertension guidelines can be seen in the Figure where the risks of elevated blood pressure identified in the 1920s and the benefit of blood pressure reduction from the Veterans Administration studies was associated with declines in population stroke mortality.2–5 As evidence in the Table, the decline in stroke mortality coincides with the reduction of population blood pressure pressures which was consistent with the lowered blood pressure thresholds and targets described in the sequential recommendations from the Guidelines.6–12 View this table: Table. Mean and 90th …

Treatment of hypertension in older people

AbstractHypertension is a major modifiable risk factor for cardiovascular events and mortality, particularly in older people. Effective blood pressure lowering reduces the risk of death and cardiovascular events, including stroke and acute myocardial infarction. The absolute benefits of blood pressure reduction are greater with increasing age. In older people (≥ 65 years), blood pressure lowering should be considered if clinic systolic blood pressure is consistently ≥ 150 mmHg. Reduction of systolic blood pressure initially to &lt; 150 mmHg, and then to &lt; 140 mmHg if tolerated, improves outcomes and is generally safe. Choices of blood pressure lowering medications are similar to those in younger people with the exceptions that beta‐blockers may be relatively ineffective with predominant systolic hypertension and some older people may be intolerant of diuretics. Ongoing monitoring is essential to assess for adequacy of blood pressure control, tolerability of medications and adherence to treatment. Temporary adjustments to therapy may be required with intercurrent illness. Refractory systolic hypertension due to large artery stiffness is a particular problem in older people. Understanding the pathophysiological changes of ageing and their impact on medication efficacy and safety are important. In frail older patients, particularly those with very limited life expectancy, treatment decisions should be individualised and the effects of any treatment carefully monitored.

Teaching an Old Drug New Tricks: Can Paroxetine Ease the Burden of Cardiovascular Disease in Diabetes?

Diabetes doubles the risk of cardiovascular disease (CVD) independently of other risk factors (1). A 50-year-old with diabetes is likely to die, on average, 6 years earlier than a counterpart without diabetes, with vascular deaths being the major contributor to reduced survival (2). In keeping with the predicted rise in diabetes prevalence, the proportion of CVD deaths attributable to diabetes (currently 10% in developed countries [2]) is likely to increase substantially. Although intensive research efforts have identified the molecular mechanisms contributing to diabetes-related CVD, these discoveries have not been mirrored by major pharmaceutical advances. As a blockbuster drug to reduce CVD in diabetes has failed to emerge, other approaches need to be considered as a matter of urgency. Although robust evidence supports the benefits of blood pressure reduction and lipid lowering in diabetes, the appropriateness of intensive glucose lowering as a tool to reduce cardiovascular risk is now questionable. In individuals newly diagnosed with diabetes, the UK Prospective Diabetes Study trial showed that intensive glycemic control with insulin or sulphonylurea resulted in a nonsignificant 16% risk reduction in myocardial infarction (3). Further, it was only after 10 years of follow-up that a 15% relative risk reduction emerged, suggesting a possible legacy effect of intensive control early in the disease process (4). In contrast, a series of large randomized trials investigating intensive glucose control in patients with diabetes of longer duration and/or established CVD has failed to demonstrate benefit. The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation and Veterans Affairs …

Renal sympathetic denervation for treatment of resistant hypertension: a systematic review.

Catheter-based renal sympathetic denervation (RSD) is a novel technique that is being investigated as treatment for resistant hypertension. To systematically evaluate the existing literature on the safety and efficacy of RSD in persons with resistant hypertension, online searches of Medline and the Cochrane Library Database (up to June 2012) were performed. Randomized controlled trials, observational studies, and conference proceedings published in English language were included. Nineteen studies (N=683 persons) were included. Follow-up duration ranged from 1 to 24 months. All studies reported significant reductions in systolic and diastolic pressures. Maximal reduction of blood pressure ranged from 18 mm Hg to 36 mm Hg (systolic) and 9 mm Hg to 15 mm Hg (diastolic). Sustained benefit of blood pressure reduction at 12 months was seen in 5 studies. No worsening of renal function was reported and there were few procedure-related adverse events such as pseudoaneurysm formation, hypotension, and bradycardia. Data from short-term studies suggest that RSD is a safe and effective therapeutic option in carefully selected patients with resistant hypertension. Long-term studies with large patient populations are needed to study whether this benefit is sustained with a demonstrable difference in cardiovascular disease event rates.

Hypertension and orthostatic hypotension in older patients

Hypertension and orthostatic hypotension in older patients

Combination Therapy in the Management of Hypertension

Hypertension is a highly prevalent and powerful contributor to the growing worldwide burden of cardiovascular disease. Antihypertensive therapy significantly reduces the risk of cardiovascular morbidity and mortality that accompanies arterial hypertension. Despite the benefits of blood pressure reduction, approximately 70% of hypertensive adults worldwide are uncontrolled [Hajjar I et al. JAMA 2003]. This article discusses the emerging role of combination therapy in the management of difficult-to-treat hypertension.

Antihypertensive medications: benefits of blood pressure lowering and hazards of metabolic effects

Blood pressure reduction is associated with significant reduction in adverse cardiovascular outcomes. Certain blood pressure-lowering drugs have adverse effects on glucose homeostasis, and have been associated with the development of both prediabetes and diabetes during use. There is controversy over the significance of diabetes that develops during treatment with antihypertensives and whether the benefits of blood pressure reduction offset the hazards of dysglycemia that can lead to diabetes. Many treatment guidelines have recently undergone revisions to include consideration for the metabolic effects of antihypertensive drugs, particularly in high-risk populations. This review summarizes the data related to the benefits of blood pressure reduction as well as the adverse metabolic effects and new-onset diabetes associated with some medications.

Hormone replacement therapy (HRT) with drospirenone offers the additional benefit of blood pressure reduction in postmenopausal women

Hormone replacement therapy (HRT) with drospirenone offers the additional benefit of blood pressure reduction in postmenopausal women

Combined Effects of Systolic Blood Pressure and Total Cholesterol on Cardiovascular Disease Risk

Half of all adult deaths (and much severe disability) are caused by cardiovascular diseases, and most of these deaths involve ischemic heart disease or stroke. The Asia-Pacific region accounts for about half of the global burden of cardiovascular disease and the proportion is likely to increase during the next few decades.1,2 Smoking and elevated levels of systolic blood pressure (SBP) and total blood cholesterol are major causes of cardiovascular disease,3 yet much of our knowledge about the associations between these risk factors and cardiovascular diseases comes from studies carried out in North American and western European countries. In most Asian countries, however, the mean levels of total cholesterol are lower than those found in Western countries and the incidence of coronary heart disease (CHD) is also lower, whereas the incidence of stroke, particularly hemorrhagic stroke, is higher. Article p 3384 The Asia Pacific Cohort Studies Collaboration report in this issue of Circulation investigates the combined effects of SBP and total cholesterol on risk of cardiovascular disease in a meta-analysis of 36 cohort studies (29 conducted in Asia and 7 from Australia and New Zealand) involving 380 000 individuals.4 This meta-analysis differs from previous studies in several ways: It is the largest study from this region, involving >3000 CHD events and 4000 stroke events; individual records were available for each of the participants in each study, with cause and age of death (if applicable); and information on several thousand repeat measurements of blood pressure and cholesterol made during prolonged follow-up allowed correction for “regression dilution.” These features …

Report From the Cardiovascular and Renal Drugs Advisory Committee

The Advisory Committee was asked to consider the desirability of class labeling for antihypertensive drugs. Antihypertensive drugs, with few exceptions, have no clinical outcomes claims in their labeling because approval of these agents is usually based on demonstration of efficacy at lowering blood pressure, not reducing morbidity or mortality. Initial placebo-controlled trials of antihypertensive agents were conducted more than 2 decades ago. Accordingly, it has been considered ethically inappropriate to perform placebo-controlled studies of modern antihypertensive agents. These factors have resulted in a clinical conundrum in which agents believed to be highly effective at reducing morbidity and/or mortality cannot claim such benefits. The Advisory Committee meeting was convened to consider how labeling should address the relationship between blood pressure and outcome. The committee felt strongly that not having outcome data available in antihypertensive drugs labels prevents optimal education of practitioners regarding the benefits of important therapeutic agents. Several committee members pointed out that undertreatment of blood pressure remains a major health problem that might be addressed by more descriptive class labeling of antihypertensive agents. The committee agreed that scientific knowledge about antihypertensive drugs is extensive and that lowering blood pressure represents one of the best-studied surrogate outcome measures in clinical medicine. However, the committee expressed some concern regarding “unintended consequences” of class labeling and discussed the need for robust preapproval safety studies and postmarketing surveillance. The industry representative on the committee cautioned that class labeling might represent a disincentive to the pharmaceutical industry to engage in future clinical trials. The committee reviewed the effects of blood pressure reduction on specific cardiovascular and renal outcome measures. After considerable discussion, the committee agreed that reduction in the incidence of stroke and myocardial infarction is the most clearly attributable benefits of blood pressure reduction. Evidence for reduction in cardiovascular mortality and renal disease …

Benefits of blood pressure reduction in diabetic patients.

Hypertension is common among patients with type 2 diabetes mellitus, increasing their risk of cardiovascular morbidity and mortality. Such patients are also at risk of renal impairment and end-stage renal disease. Long-term, tight blood pressure control (ideally to a target of < 130/85 mmHg) in patients with type 2 diabetes is a highly effective strategy for reducing the risk of cardiovascular complications and is now embodied in the many guidelines of hypertension and diabetes management. More recent studies indicate that the choice of antihypertensive agent is also important. Drugs that block the renin-angiotensin-aldosterone system, such as the angiotensin-II receptor blockers (ARBs), may prevent the onset of diabetes and confer greater cardiovascular benefit among patients who already have this disease compared with some older antihypertensive agents. For example, in type 2 diabetic patients with renal dysfunction, ARBs exert a renal protective effect that extends beyond blood pressure reduction and may retard diabetic nephropathy. Antihypertensive therapy, together with lifestyle modification to address obesity and physical inactivity, can significantly reduce the risk of cardiovascular complications in patients with type 2 diabetes. The challenge is to achieve beneficial, hygienic measures in populations with diverse backgrounds and improve compliance with proven treatments that inevitably involve multiple drugs. Combination therapies comprising agents that offer good tolerability and do not exacerbate existing metabolic disturbances, as well as demonstrating benefit in preventing events in diabetic patients beyond blood pressure reduction itself, seem a likely way forward.

Benefits of blood pressure reduction in elderly patients.

Hypertension in the elderly is characterized principally by increased systolic blood pressure (SBP). Consequently, isolated systolic hypertension (ISH) is the most common subtype in this population. The major haemodynamic determinant underlying ISH is increased large-artery stiffness. This is expressed as an increase in SBP and decrease in diastolic blood pressure (DBP), leading to widening pulse pressure. Epidemiological studies show that ISH and increased pulse pressure in the elderly constitute independent cardiovascular risk factors and may be more robust in predicting the adverse cardiovascular sequelae of hypertension than elevated DBP alone. Reducing high blood pressure (> 140/90 mmHg), including ISH (SBP > 140 mmHg, DBP < 90 mmHg), with conventional and newer antihypertensive agents significantly reduces the risk of major coronary events, stroke, coronary heart disease and all-cause mortality. Among the elderly population, there appears to be no age threshold beyond which treatment of hypertension, including ISH, should not be considered beneficial. Clinical management has to take into account some specific aspects related to its pathophysiology and the patient characteristics of this population. Although the therapeutic goal is < 140/90 mmHg, a decrease of 20-30 mmHg in SBP, even if the overall goal is not achieved, is associated with improved prognosis.

Compliance and persistence with newer antihypertensive agents.

Individuals with hypertension need to stay on therapy with antihypertensive medication to obtain the full benefits of blood pressure reduction. There are important differences in tolerability across antihypertensive drug classes, and these differences influence the extent to which patients are willing to continue taking their drugs. Three separate sources of evidence--postmarket surveillance studies, medical/prescription database studies, and discontinuation of study medication in long-term endpoint clinical trials--support the proposition that angiotensin II antagonists, the newest class of antihypertensives, are well tolerated, and that patients whose initial treatment is an angiotensin II antagonist are more likely to persist with therapy than patients who use other classes of antihypertensives. Recent landmark trials with losartan in hypertensive patients with left ventricular hypertrophy (Losartan Intervention For Endpoint reduction [LIFE]) and in diabetes (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL]) demonstrated excellent tolerability, a high level of persistence, and clinical benefits exceeding those provided by blood pressure control alone for the prototype angiotensin II antagonist in clinical settings.

Blood pressure control--effects on diabetic nephropathy progression: how low does blood pressure have to be?

Hypertension and diabetes are independent risk factors for both cardiovascular disease and renal complications. Coexistence of these comorbid conditions predisposes the patient to a much greater risk of progression to end-stage renal disease. Combined with the increased cardiovascular mortality, this has led to recent Joint National Committee-VI recommendations for the initiation of antihypertensive therapy for people with diabetes at a blood pressure of 130/85 mm Hg, a level lower than that recommended for the nondiabetic population. Results of a review of recently published investigations on the effects of blood pressure on diabetic nephropathy progression are presented in this article. This review finds evidence to support reducing the mean arterial blood pressure to levels below 95 mm Hg, a level that is even lower than the blood pressure of 130/80 mm Hg (mean arterial pressure of 97 mm Hg) recommended by the American Diabetes Association and National Kidney Foundation. The effect of blood pressure on renal disease progression is linear and appears to have no lower threshold for the benefits of blood pressure reduction on limiting nephropathy progression. The answer to the question of how low does blood pressure have to be to minimize the effects of blood pressure on diabetic nephropathy progression might be "the lower, the better."